The Ras homolog gene family member A (RhoA) is a small GTPase. RhoA plays major roles in cytoskeletal regulation, transcriptional control, and cell cycle maintenance. RhoA is widely expressed in the female reproductiv...The Ras homolog gene family member A (RhoA) is a small GTPase. RhoA plays major roles in cytoskeletal regulation, transcriptional control, and cell cycle maintenance. RhoA is widely expressed in the female reproductive system (FRS). In vitro studies have implicated RhoA in several FRS functions and studies defining the in vivo functions of RhoA in the FRS are emerging. In the ovary, RhoA is essential for corpus luteum development and progesterone synthesis and is implicated in ovarian cancer. Some studies on the oviduct/fallopian tube suggest potential functions of RhoA in post-ovulation cumulus cells and embryo transport. In the uterus (corpus uterus), RhoA may be involved in embryo implantation (eg, decidualization) and parturition (eg, uterine contraction) and is also implicated in uterine disorders (eg, endometriosis and leiomyoma). Downregulation of RhoA in the cervix is correlated with cervical ripening during parturition, and numerous studies have implicated RhoA in cervical cancer. In the placenta, RhoA is implicated in preeclampsia and placenta accreta. In the vagina, RhoA downregulation correlates with vaginal smooth muscle relaxation and sexual response. RhoA in the mammary glands has been implicated in development and lactation as well as breast cancer. RhoA signaling is a potential therapeutic target for managing pathological conditions of the FRS. This review provides a comprehensive coverage of the current understanding of the spatiotemporal functions of RhoA in the FRS. Extensive knowledge regarding the in vivo cell type- and stage-specific functions of RhoA in FRS remains to be elucidated.展开更多
Objective:The association of season and vitamin D status with pregnancy outcomes remains poorly understood.This study aimed to investigate the correlation between vitamin D deficiency(VDD)during pregnancy in different...Objective:The association of season and vitamin D status with pregnancy outcomes remains poorly understood.This study aimed to investigate the correlation between vitamin D deficiency(VDD)during pregnancy in different seasons and adverse pregnancy outcomes(APOs).Methods:The risk of APOs,including preterm delivery,gestational diabetes mellitus,pre-eclampsia,small for gestational age,and large for gestational age,was retrospectively evaluated in 5234 women.The vitamin D status of all women was assessed during pregnancy,and VDD was considered at a maternal serum concentration of 25-hydroxyvitamin D concentration of<50.0 nmol/L.Binary logistic regression was used to assess the risk of APOs,which were expressed as adjusted odds ratios(aOR)with 95%confidence intervals(CIs).Results:VDD was observed in 4202(80.28%)women.VDD during pregnancy was associated with preterm delivery(aOR=2.10,95%CI:1.52-2.89)and small for gestational age(aOR=1.40,95%CI:1.00-1.96).The association between VDD and preterm delivery was significant in spring(aOR=1.97,95%CI:1.03-3.74),summer(aOR=2.46,95%CI:1.32-4.58),and winter(aOR=2.96,95%CI:1.55-5.66).Meanwhile,we did not observe an association of VDD with gestational diabetes mellitus,pre-eclampsia,or large for gestational age.Conclusions:Season and VDD are associated with APOs.Our findings suggest the optimal timing for vitamin D assessment and interventions to optimize pregnancy outcomes.展开更多
Objective:Advanced maternal age is associated with reduced ovarian reserve and lower oocyte quality.Whether body mass index(BMI)further influences assisted reproductive technology(ART)outcomes in this population remai...Objective:Advanced maternal age is associated with reduced ovarian reserve and lower oocyte quality.Whether body mass index(BMI)further influences assisted reproductive technology(ART)outcomes in this population remains unclear.Methods:This retrospective study analyzed 222 patients aged≥37 years who underwentin vitro fertilization or intracytoplasmic sperm injection with embryo transfer(IVF/ICSI-ET)at the First Affiliated Hospital of Xiamen University between January 2019 and December 2023.Patients were classified by BMI as underweight(<18.5 kg/m^(2);n=13),normal(18.5-24.9 kg/m^(2);n=154),or overweight(>24.9 kg/m^(2);n=55).Controlled ovarian stimulation protocols were individualized according to ovarian reserve.Laboratory and clinical outcomes were compared across groups,and multivariable logistic regression was used to identify factors associated with clinical pregnancy and live birth.Results:BMI,total gonadotropin dose,and use of IVFvs.ICSI differed among groups(allP<0.05).However,oocyte retrieval rate,metaphase II(MII)oocyte rate,cleavage rate,available embryo rate,high-quality embryo rate,biochemical pregnancy rate,clinical pregnancy rate,live birth rate,and miscarriage rate showed no significant differences(allP>0.05).In multivariable analysis,age,infertility duration,and progesterone level on the day of human chorionic gonadotropin(hCG)trigger were independent predictors of clinical pregnancy.Moreover,age and progesterone level on the hCG day were independently associated predictors of live birth(allP<0.05).Conclusions:Among women aged≥37 years,higher BMI did not significantly affect key laboratory or pregnancy outcomes after IVF/ICSI-ET.Clinical results were mainly influenced by age,infertility duration,and progesterone level on the hCG trigger day.展开更多
Objective:According to the previous studies,it has been found that long non-coding RNA H19(lncRNA H19)-ITGB3-miR-124-3p axis can regulate cell proliferation and invasion of the ectopic endometrium,which could be the p...Objective:According to the previous studies,it has been found that long non-coding RNA H19(lncRNA H19)-ITGB3-miR-124-3p axis can regulate cell proliferation and invasion of the ectopic endometrium,which could be the potential pathway for treating endometriosis by a key medicine.The aim of this study was to investigate the roles of metformin,aspirin,artemisinin,and berberine in regulating the expression of lncRNA H19 in ectopic endometrial stromal cells(ecESCs)and explore novel medicines for the treatment of endometriosis.Methods:Isolation of ESCs from the ectopic endometrium of patients with endometriosis and treatment with metformin at 0.1 mmol/L,aspirin at 5.00 mmol/L,artemisinin at 20μmol/L,and berberine at 20μmol/L for 0,12,24,and 48 hours.LncRNA H19 levels in ecESCs after treatment were evaluated using real-time polymerase chain reaction,and changes in cell proliferation and invasion were determined using Cell Counting Kit-8 and Transwell assays.Results:lncRNA H19 levels in ecESCs in the metformin,aspirin,artemisinin,and berberine groups were significantly lower than those in the control group,with inhibition of cell proliferation and invasion;metformin and berberine showed the highest efficiency.Conclusions:Metformin and berberine inhibited ecESC proliferation and invasion by downregulating lncRNA-H19 levels,offering a novel treatment for endometriosis.展开更多
Lichen sclerosus is a chronic inflammatory autoimmune skin disease that primarily affects the genital area, especially the vulva. It predominantly affects women and shows a bimodal incidence distribution. The principa...Lichen sclerosus is a chronic inflammatory autoimmune skin disease that primarily affects the genital area, especially the vulva. It predominantly affects women and shows a bimodal incidence distribution. The principal clinical manifestations include vulvar itching, pain, and depigmentation, potentially leading to scarring, anatomical distortion, and malignant transformation if left untreated. The etiology is uncertain but may involve autoimmune factors, genetics, infections, hormones, trauma, chronic irritation, and oxidative stress. The diagnosis is primarily clinical, and histological confirmation is not always necessary when characteristic clinical signs are present. Although lichen sclerosus is incurable, it is manageable with appropriate treatment. This review summarizes the epidemiology, clinical features, complications, etiology, diagnosis, and treatment of lichen sclerosus.展开更多
Objective:Cisplatin(CIS),as a common chemotherapy drug,induces detrimental effects on the testis.Besides,exosomes represent various beneficial effects,such as anti-inflammation and proliferation.In this experimental s...Objective:Cisplatin(CIS),as a common chemotherapy drug,induces detrimental effects on the testis.Besides,exosomes represent various beneficial effects,such as anti-inflammation and proliferation.In this experimental study,the authors aimed to evaluate the anti-inflammatory effects of circulating blood serum-derived exosomes on orchitis caused by CIS exposure.Methods:Male mice(n=18)were categorized into three main groups:control(no treatment),CIS(mice with orchitis caused by CIS injection),and CIS+exosome(orchitis-induced animals followed by exosome treatment).Exosomes were extracted from circulating blood,and orchitis was induced by intraperitoneal injection of CIS(7.5 mg/kg/day)for five consequence days.A day after the last dose of CIS,the exosome(10 IU/20 g mice)was injected intratesticularly.After a week,the samples,including blood serum and testis,were gathered.The levels of oxidative stress were assessed using malondialdehyde(MDA)and nitric oxide(NO)assays.Sperm parameters(morphology,viability,motility,and count),testosterone levels,and inflammatory(tumor necrosis factor-α[TNF-α],interleukin(IL)-6,and IL-10)gene expression were also evaluated.Histopathological and testicular apoptotic index(AI)were evaluated using hematoxylin and eosin(H&E)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)stainings,respectively.Finally,data analysis was applied by SPSS(v.19)software,andP<0.05 was considered as a significant level.Results:Following CIS administration,the sperm indices and testosterone levels were decreased(P<0.05);besides,NO,MDA,AI,and inflammatory gene expression were increased(P<0.05)in the CIS group compared to control animals.Following the prescription of exosomes in CIS animals,the sperm indices and testosterone levels were increased(P<0.05),and NO,MDA,AI,and inflammatory genes were decreased(P<0.05).Histopathological assessments also revealed disruption of seminiferous tubules and free from sperms following CIS administration.Also,the histological structure of damaged seminiferous tubules was changed to normal status following Exoxome prescription in CIS-exposure animals.Conclusion:Immediate intratesticular injection of blood-derived exosomes can alleviate orchitis CIS-exposed animals through anti-inflammatory features.展开更多
Objective: ATP6V0d2 is a subunit of the vacuolar-type H+-ATPase (V-ATPase) that pumps H+ ions into lysosomes. TRPML1 (MCOLN1/Mcoln1) transports cations out of lysosomes.Mcoln1^(-/-) mice recapitulate the lysosomal sto...Objective: ATP6V0d2 is a subunit of the vacuolar-type H+-ATPase (V-ATPase) that pumps H+ ions into lysosomes. TRPML1 (MCOLN1/Mcoln1) transports cations out of lysosomes.Mcoln1^(-/-) mice recapitulate the lysosomal storage disorder mucolipidosis type IV (MLIV) phenotype. We previously demonstrated thatMcoln1^(-/-) female mice quickly became infertile at 5 months old (5M) with degenerating corpora lutea (CL) and progesterone (P4) deficiency. We tested our hypothesis thatAtp6v0d2 deficiency could partially compensate forMcoln1 deficiency to restore CL functions inAtp6v0d2^(-/-)Mcoln1^(-/-) mice.Methods: Control andAtp6v0d2^(-/-)Mcoln1^(-/-) female mice underwent fertility test from 2M to 7M. A subset of them was dissected at 5M on day 3.5 post-coitum (D3.5). The D3.5 ovaries from 5M control,Mcoln1^(-/-), andAtp6v0d2^(-/-)Mcoln1^(-/-) mice were evaluated for CL morphology, lipid droplet staining, and markers of mitochondria and P4 steroidogenesis in the luteal cells.Results: The fertility test ofAtp6v0d2^(-/-)Mcoln1^(-/-) female mice (2M–7M) revealed normal mating activity but reduced fertility compared with the control;yet ~25% of them remained fertile at 5M to 7M but with dystocia. We analyzed a subset of 11Atp6v0d2^(-/-)Mcoln1^(-/-) mice (5M) in the fertility test on D3.5: three (27.3%) had normal P4 levels and all examined CL parameters, indicating full restoration of CL function compared withMcoln1^(-/-), whereas eight had P4 deficiency, with two (18.2%) infertile and six (54.5%) once fertile. In contrast toMcoln1^(-/-) CLs, which had extensive amorphous cellular debris, indicating cell degeneration,Atp6v0d2^(-/-)Mcoln1^(-/-) CLs had reduced amorphous cellular debris regardless of P4 levels. However, similar toMcoln1^(-/-) CLs, P4-deficientAtp6v0d2^(-/-)Mcoln1^(-/-) CLs showed impaired differentiation, enlarged lipid droplets, disorganized expression of endothelial basal lamina marker collagen IV, and reduced expression of mitochondrial marker heat shock protein 60 (HSP60) and steroidogenesis rate-limiting protein StAR, indicating that additionalAtp6v0d2 deficiency compensates forMcoln1 deficiency-induced cell degeneration, but is insufficient to restore luteal cell differentiation and P4 steroidogenesis in P4-deficientAtp6v0d2^(-/-)Mcoln1^(-/-) CLs.Conclusion: This study shows thatAtp6v0d2^(-/-)Mcoln1^(-/-) CLs had varied improvements compared withMcoln1^(-/-) CLs, and it providesin vivo genetic evidence of the coordination between different lysosomal channels in CL function.展开更多
Objective:Cyclophosphamide(CP)is an anticancer drug that induces oxidative stress,leading to gonadal toxicity.This study aimed to evaluate the effectiveness of co-treatment with zinc oxide nanoparticles(nZno)and melat...Objective:Cyclophosphamide(CP)is an anticancer drug that induces oxidative stress,leading to gonadal toxicity.This study aimed to evaluate the effectiveness of co-treatment with zinc oxide nanoparticles(nZno)and melatonin(Mel)on lipid peroxidation and antioxidant enzyme levels against CP-induced testicular damage.Methods:In this study,42 adult male rats were divided into six groups.The control group received intraperitoneal(i.p.)saline solution.The CP group was administered CP at 60 mg/kg/week.The Mel+CP and nZno+CP groups received CP along with 10 mg/kg Mel and 5 mg/kg nZno,respectively.The Mel+nZno+CP group received CP plus 10 mg/kg Mel and 5 mg/kg nZno,simultaneously.The Mel+nZno group received 10 mg/kg Mel and 5 mg/kg nZno simultaneously.Eight weeks after the treatment,hormonal assays,total antioxidant capacity(TAC),histological studies,lipid peroxidation levels,and antioxidant enzyme status were assessed.Results:Biochemical results showed that CP decreased spermatogenic lineage cells,TAC,levels of antioxidant enzymes catalase(CAT),glutathione(GSH),and glutathione peroxidase(GSH-Px),and reproductive hormone levels luteinizing hormone(LH),follicle-stimulating hormone(FSH)and testosterone,and increased malondialdehyde(MDA)content.In contrast,co-treatment with Mel and nZno in the Mel+nZno+CP group resulted in a significant improvement in all examined parameters(P<0.05).Conclusion:The results indicate that the simultaneous administration of Mel and nZno could be used as a potential protective agent against CP-induced reproductive toxicity.展开更多
Objective:To analyze the clinical characteristics,diagnostic challenges,treatment strategies,and long-term outcomes of ovarian leiomyomas through a 20-year retrospective study,aiming to improve awareness and managemen...Objective:To analyze the clinical characteristics,diagnostic challenges,treatment strategies,and long-term outcomes of ovarian leiomyomas through a 20-year retrospective study,aiming to improve awareness and management of this rare tumor.Methods:This single-center retrospective study included 39 cases of ovarian leiomyomas confirmed by histopathology and immunohistochemistry between January 2003 and December 2023 at the Obstetrics and Gynecology Hospital affiliated with Fudan University.Clinical,imaging,surgical,and follow-up data were systematically reviewed.Pathological criteria,including mitotic index and immunohistochemical markers,were used for tumor classification.Results:Among the 39 patients,10 were diagnosed with primary ovarian leiomyomas and 29 with secondary forms.The average age was 52.3 years,and most tumors were unilateral and incidentally discovered.Clinical symptoms included abdominal pain,distension,and abnormal uterine bleeding,while 66.7%of patients were asymptomatic.Imaging via ultrasound revealed solid or hypoechoic masses,but lacked specificity.MRI was used in only three cases.Histologically,tumors showed well-differentiated smooth muscle cells with low mitotic activity.Immunohistochemical staining confirmed smooth muscle origin.All patients underwent surgical excision.No recurrences were observed during a median follow-up of 12 years.Conclusion:Ovarian leiomyomas are rare and often asymptomatic,leading to frequent misdiagnosis.Accurate diagnosis relies on histopathology and immunohistochemistry.Surgical resection offers excellent outcomes,and ovary-sparing approaches should be considered in younger patients.Greater clinical awareness and additional research are essential to improve diagnostic accuracy and therapeutic strategies.展开更多
Objective:To evaluate the clinical efficacy of vaginal repair as a salvage treatment for cesarean scar defects in patients with previously failed repair surgery.Methods:This retrospective cohort study included 16 pati...Objective:To evaluate the clinical efficacy of vaginal repair as a salvage treatment for cesarean scar defects in patients with previously failed repair surgery.Methods:This retrospective cohort study included 16 patients with cesarean scar defects who underwent vaginal repair as salvage therapy after prior repair surgery failure between March 2019 and September 2022 at the Department of Obstetrics and Gynecology,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine.The previous failed procedures included vaginal repair,hysteroscopic repair,and laparoscopic repair.A control group of 108 patients who underwent primary vaginal repair during the same period was also analyzed.Perioperative outcomes and post-operative repair efficacy were compared.The length,width,and depth of the cesarean scar defect,as well as the thickness of the residual myometrium,were measured by transvaginal ultrasonography.Results:No significant differences were observed between the two groups in demographic characteristics.In both groups,the duration of menstruation significantly decreased after vaginal repair(from 12.8±5.3 to 6.75±1.8 days in the salvage therapy group,and from 13.5±3.8 to 7.1±1.7 days in the primary surgery group),while the thickness of the residual myometrium significantly increased(from 3.0±2.0 to 7.7±2.6 mm in the salvage therapy group,and from 2.6±1.2 to 7.7±2.5 mm in the primary surgery group).Post-operatively,there were no significant differences between the two groups in either menstrual duration(6.8±1.8vs.7.1±1.7 days)or residual myometrial thickness(7.7±2.6vs.7.7±2.5 mm).The data also indicated that performing salvage therapy within≤21 months of the initial surgery was associated with a better prognosis.Conclusions:Vaginal repair as salvage therapy is a feasible and effective option for patients with cesarean scar defects after failed repair surgery.展开更多
Recent progress inin vitro maturation(IVM)technology using human immature oocytes for clinical applications has been reported.The success rate of IVM technology depends on the source of immature oocytes,and to date,no...Recent progress inin vitro maturation(IVM)technology using human immature oocytes for clinical applications has been reported.The success rate of IVM technology depends on the source of immature oocytes,and to date,no single protocol has demonstrated superior results over others.Attempts to adapt IVM protocols developed in animal models have not let to significant breakthroughs in culture conditions and systems.Cumulus cells are known to play an important role in oocyte maturation;however,the results of co-culture with different types of cells for IVM of human immature oocytes remain controversial.As one of the assisted reproductive technologies(ART),IVM is only involved in a specific procedure for infertility treatment and fertility preservation.With the development of IVM technology,it has been proposed that the combination of mild-stimulation cycle with retrieval of both mature and immature oocytes,followed by IVM,may offer a viable alternative to the conventional stimulation cycle treatment.展开更多
Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different ...Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring.Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group;Group 2, the IG group, in which utrogestan was administeredvia intragastric gavage;Group 3, the IM group, in which P4 was administeredvia intramuscular injection;and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis.Results: No significant alterations in fertility outcomes were observed through three P4 administration routes-intragastric gavage, intramuscular injection, and vaginal administration-in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatmentvia the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereasOlivella appeared exclusively in the control group rather than in the P4 treatment groups.Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.展开更多
Objective:This study aimed to investigate the influence of lung function on the relationship between allergies and hypertension,thereby elucidating significant potential mechanisms from a genetic standpoint.We investi...Objective:This study aimed to investigate the influence of lung function on the relationship between allergies and hypertension,thereby elucidating significant potential mechanisms from a genetic standpoint.We investigated the causal relationship between childhood allergies(age<16 years)and essential hypertension and identified and quantified the role of lung function(forced vital capacity[FVC]and forced expiratory volume in the first second/forced vital capacity[FEV1/FVC])as potential mediators.Methods:Using data from a genome-wide association study and the Fenn Genn consortium,a two-sample Mendelian randomization(MR)analysis of genetically predicted childhood allergies(7128 cases and 211,703 controls)and essential hypertension(116,714 cases and 1,032,659 controls)was performed.Furthermore,we used two-step MR to quantify the effect of lung function-mediated childhood allergies on essential hypertension.The FVC and FEV1/FV sample size was 371,898.Results:Childhood allergies were associated with increased odds of developing essential hypertension(odds ratio[OR]=1.0900,95%confidence interval[CI]=1.0034–1.1842,P=0.0414).No strong evidence that genetically predicted essential hypertension affected childhood allergy risk was identified(OR=1.0631,95%CI=0.9829–1.1498,P=0.1264).The proportion of genetically predicted childhood allergies mediated only by FVC was 5.67%(95%CI,5.13%–5.73%).Conclusion:A causal relationship between childhood allergies and essential hypertension was identified,with a proportion of the effect mediated by FVC.Therefore,implementing early interventions in children with allergies is imperative to mitigate the long-term risk of developing hypertension.Further research is required to identify additional risk factors as potential mediators.展开更多
Objective:Endometriosis is a chronic gynecological disease requiring relatively long therapy of at least 3 to 6 months,and has a high recurrence rate.Further research using animal models is needed to better understand...Objective:Endometriosis is a chronic gynecological disease requiring relatively long therapy of at least 3 to 6 months,and has a high recurrence rate.Further research using animal models is needed to better understand the disease.During the COVID-19 pandemic,laparoscopic surgeries were suspended to minimize infection risk.This study aims to establish an experimental animal model of endometriosis using stored chocolate cyst pulp.Methods:This laboratory experimental study included 12 female Mus musculus mice.Immunodeficient mice were intraperitoneally injected with a previously prepared chocolate cyst slurry.On the 15th day,the mice were euthanized,and anatomical pathological examination was performed using hematoxylin and eosin(HE)staining.Results:Anatomical pathology examination revealed stromatosis in the fat tissue of all 12 mice treated with stored chocolate cyst slurry,confirming the presence of endometriosis.The protocol demonstrated a 100%success rate in developing a mouse model of endometriosis.Conclusion:The successful development of a mouse endometriosis model from stored chocolate cyst slurry using this protocol is expected to contribute to experimental animal studies.展开更多
Polycystic ovary syndrome(PCOS)is a common gynecological disease that affects women of reproductive age and is characterized by hyperandrogenism,ovulatory dysfunction,and polycystic changes in the ovaries.In recent ye...Polycystic ovary syndrome(PCOS)is a common gynecological disease that affects women of reproductive age and is characterized by hyperandrogenism,ovulatory dysfunction,and polycystic changes in the ovaries.In recent years,along with irregular menstruation and infertility,metabolic abnormalities associated with PCOS have garnered increasing attention.Insulin resistance is the most prevalent metabolic abnormality in patients with PCOS and is closely related to disease progression and severity.Insulin-sensitizing drugs improve obesity-and hyperinsulinemia-related symptoms in patients with PCOS.Although the exact etiology of PCOS remains incompletely understood,genomic and metabolomic studies have identified various metabolic changes in the serum and follicular fluid of patients with PCOS and in animal models.These findings shed light on the pathogenesis of PCOS and help identify new preventive and therapeutic approaches.This review explores the role of insulin resistance in the pathophysiology of PCOS,focusing on its effects on ovulation and hyperandrogenism.It also summarizes recent therapeutic advancements,evaluates their efficacy,and discusses strategies for the long-term management of insulin resistance in PCOS.展开更多
Objective:To study the effects of preconceptional thyroid-stimulating hormone(TSH)levels on antral follicle count(AFC)and pregnancy outcomes in a firstin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)...Objective:To study the effects of preconceptional thyroid-stimulating hormone(TSH)levels on antral follicle count(AFC)and pregnancy outcomes in a firstin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)cycle.Methods:A retrospective cohort study was conducted to explore the effects of preconceptional TSH levels on AFC and pregnancy outcomes in 1340 patients.The patients were divided into three groups:group 1,0.55≤TSH<2.5μIU/mL(n=868);group 2,2.5≤TSH<4.0μIU/mL(n=334);and group 3,TSH≥4.0μIU/mL(n=138).Results:There were significant differences in AFC(P=0.002),number of zygotes(P=0.008),and fertilization rate(P=0.015)among the three groups.Among the three groups,there were no obvious differences in live birth(P=0.559),high-quality embryo(P=0.108),or clinical pregnancy(P=0.939)rates.Binary logistics regression analysis showed that TSH correlated with AFC when TSH was≥4μIU/mL(P=0.033);however,TSH levels had no effect on live birth or clinical pregnancy rate.Conclusions:Although the preconceptional TSH level negatively related with AFC,number of zygotes,and fertility rate,especially when TSH was>4μIU/mL,TSH was not an independent factor on the live birth rate among fertile women undergoing their first IVF/ICSI-embryo transfer treatment.The effect of TSH levels on couples undergoing assisted reproductive technology requires further investigation.展开更多
Quality control in disease diagnosis and treatment is critical for ensuring patient safety,optimizing resource utilization,and improving clinical outcomes.In endometrial cancer management,rigorous quality control ensu...Quality control in disease diagnosis and treatment is critical for ensuring patient safety,optimizing resource utilization,and improving clinical outcomes.In endometrial cancer management,rigorous quality control ensures accurate diagnosis through standardized protocols,reducing misdiagnosis and enabling early detection.Treatment is guided by evidence-based guidelines,fostering multi-disciplinary collaboration and minimizing unnecessary variations in care.Quality control also enhances patient safety by reducing medical errors and ensuring compliance with ethical and legal standards.By fostering transparency,professional development,and patient-centered care,it supports the sustainable advancement of healthcare systems,ultimately improving outcomes for patients and the broader medical community.This quality control of endometrial cancer was drafted by the Obstetrics and Gynecology Hospital of Fudan University based on the American Joint Committee on Cancer’s TNM staging(AJCC,8th edition,2017)and the International Federation of Obstetrics and Gynecology’s surgical pathological staging(FIGO,2009).展开更多
Objective:Frozen-thawed embryo transfer(FET)is widely used inin vitro fertilization(IVF)clinics but is associated with an increased risk of several pregnancy complications,including large-for-gestational age and place...Objective:Frozen-thawed embryo transfer(FET)is widely used inin vitro fertilization(IVF)clinics but is associated with an increased risk of several pregnancy complications,including large-for-gestational age and placenta-related diseases.However,the effects of FET on placentation remain unclear.Therefore,we used single-cell RNA-sequencing(scRNA-seq)technology to investigate the impact of FET on placental gene expression in different subtypes of trophoblasts.Methods:A mouse model of IVF and FET was constructed to collect placenta tissues.scRNA-seq was performed on placentas from two dams undergoing IVF-embryo transfer and two dams undergoing IVF-FET.Differentially expressed gene(DEG)analyses were performed in different subtypes of trophoblasts.Identified DEGs were polymerase chain reaction(PCR)validated.Results:The fetal weights and placental efficiency were higher in the FET group than those in the IVF group at E18.5,with no significant difference in placental weights.Subsequently,55,406 placental cells were captured and annotated.Upregulated DEGs in the FET group in syncytiotrophoblasts(SynTs)and sinusoidal trophoblast giant cells(S-TGCs)within the placental labyrinth were enriched in pathways related to vascular development and oxidative stress,respectively.The expression of the imprinted geneIgf2 in SynTs,S-TGCs,and spongiotrophoblasts was significantly increased.In the junctional zone,FET upregulated the expression of prolactin genes such asPrl3b1 in glycogen trophoblasts(GlyTs)while the downregulated expression of GlyT genes following FET was associated with mesenchyme development.Conclusions:This study first identifies DEGs and enriched pathways in different subtypes of trophoblasts following FET.These genes and pathways may contribute to the increased placental efficiency and fetal weights.Future studies are required to confirm these results and further explore the key mechanisms in placental pathologies.展开更多
Despite impressive progress being made in investigating the mechanisms underlying endometriosis,the pathophysiology of this disease remains unclear.Although typical methods used for diagnosing endometriosis such as ul...Despite impressive progress being made in investigating the mechanisms underlying endometriosis,the pathophysiology of this disease remains unclear.Although typical methods used for diagnosing endometriosis such as ultrasound,magnetic resonance imaging,and blood tests are available,these are also inefficient,and effective noninvasive diagnostic methods are lacking.The advances in high-throughput omics techniques have enabled metabolomics to become an effective approach for discovering promising biomarkers.The aberrant metabolism associated with serious symptoms of endometriosis in women has been revealed in recent years.Analyzing the global metabolic patterns in patients with endometriosis may help deepen the understanding of the disease mechanism and have a significant impact on future diagnostic and treatment methods for endometriosis.Herein,we reviewed relevant studies on metabolic changes in patients with endometriosis and discussed the changes in metabolites both in biological fluids and endometriosis tissues.The findings discussed in this review have potential diagnostic implications and will enhance the understanding of the pathophysiological processes underlying the disease.展开更多
Objective:To determine the presence of female germline stem cells(FGSCs)in postnatal mammals under physiological and pathological conditions.Methods:We explored the presence of FGSCs using various models,including mic...Objective:To determine the presence of female germline stem cells(FGSCs)in postnatal mammals under physiological and pathological conditions.Methods:We explored the presence of FGSCs using various models,including mice of different ages,an ovarian mouse model with mechanical injury,and a rat model of endometriosis.Moreover,we investigated the feasibility of inducing FGSCs in vitro using cultured ovarian tissues and employed the differential adhesion method for isolating FGSCs.For labeling FGSCs within the ovary,we employed markers such as mouse VASA homolog(MVH)/ubiquitin carboxy-terminal hydrolase L1(UCHL1)and 5-Bromo-2'-deoxyuridine(BrdU).Results:Our investigations revealed that FGSCs were not detectable in any of our models,across all conditions tested.Conclusion:Our experiments provide evidence for the viewpoint that no FGSC exists in the ovaries of postnatal mice or rats,and then support that mammalian ovaries do not produce new oocytes after birth.展开更多
基金supported by the following grants:NIH R03HD097384,R03HD100652,and R01HD114750 to X.Y.
文摘The Ras homolog gene family member A (RhoA) is a small GTPase. RhoA plays major roles in cytoskeletal regulation, transcriptional control, and cell cycle maintenance. RhoA is widely expressed in the female reproductive system (FRS). In vitro studies have implicated RhoA in several FRS functions and studies defining the in vivo functions of RhoA in the FRS are emerging. In the ovary, RhoA is essential for corpus luteum development and progesterone synthesis and is implicated in ovarian cancer. Some studies on the oviduct/fallopian tube suggest potential functions of RhoA in post-ovulation cumulus cells and embryo transport. In the uterus (corpus uterus), RhoA may be involved in embryo implantation (eg, decidualization) and parturition (eg, uterine contraction) and is also implicated in uterine disorders (eg, endometriosis and leiomyoma). Downregulation of RhoA in the cervix is correlated with cervical ripening during parturition, and numerous studies have implicated RhoA in cervical cancer. In the placenta, RhoA is implicated in preeclampsia and placenta accreta. In the vagina, RhoA downregulation correlates with vaginal smooth muscle relaxation and sexual response. RhoA in the mammary glands has been implicated in development and lactation as well as breast cancer. RhoA signaling is a potential therapeutic target for managing pathological conditions of the FRS. This review provides a comprehensive coverage of the current understanding of the spatiotemporal functions of RhoA in the FRS. Extensive knowledge regarding the in vivo cell type- and stage-specific functions of RhoA in FRS remains to be elucidated.
基金supported by grants from the Shenzhen Science and Technology Program(JCYJ20220530144407016)to Q.L.the National Natural Science Foundation of China(82204049)to Q.L.
文摘Objective:The association of season and vitamin D status with pregnancy outcomes remains poorly understood.This study aimed to investigate the correlation between vitamin D deficiency(VDD)during pregnancy in different seasons and adverse pregnancy outcomes(APOs).Methods:The risk of APOs,including preterm delivery,gestational diabetes mellitus,pre-eclampsia,small for gestational age,and large for gestational age,was retrospectively evaluated in 5234 women.The vitamin D status of all women was assessed during pregnancy,and VDD was considered at a maternal serum concentration of 25-hydroxyvitamin D concentration of<50.0 nmol/L.Binary logistic regression was used to assess the risk of APOs,which were expressed as adjusted odds ratios(aOR)with 95%confidence intervals(CIs).Results:VDD was observed in 4202(80.28%)women.VDD during pregnancy was associated with preterm delivery(aOR=2.10,95%CI:1.52-2.89)and small for gestational age(aOR=1.40,95%CI:1.00-1.96).The association between VDD and preterm delivery was significant in spring(aOR=1.97,95%CI:1.03-3.74),summer(aOR=2.46,95%CI:1.32-4.58),and winter(aOR=2.96,95%CI:1.55-5.66).Meanwhile,we did not observe an association of VDD with gestational diabetes mellitus,pre-eclampsia,or large for gestational age.Conclusions:Season and VDD are associated with APOs.Our findings suggest the optimal timing for vitamin D assessment and interventions to optimize pregnancy outcomes.
基金Natural Science Foundation of Xiamen(3502Z20227342)。
文摘Objective:Advanced maternal age is associated with reduced ovarian reserve and lower oocyte quality.Whether body mass index(BMI)further influences assisted reproductive technology(ART)outcomes in this population remains unclear.Methods:This retrospective study analyzed 222 patients aged≥37 years who underwentin vitro fertilization or intracytoplasmic sperm injection with embryo transfer(IVF/ICSI-ET)at the First Affiliated Hospital of Xiamen University between January 2019 and December 2023.Patients were classified by BMI as underweight(<18.5 kg/m^(2);n=13),normal(18.5-24.9 kg/m^(2);n=154),or overweight(>24.9 kg/m^(2);n=55).Controlled ovarian stimulation protocols were individualized according to ovarian reserve.Laboratory and clinical outcomes were compared across groups,and multivariable logistic regression was used to identify factors associated with clinical pregnancy and live birth.Results:BMI,total gonadotropin dose,and use of IVFvs.ICSI differed among groups(allP<0.05).However,oocyte retrieval rate,metaphase II(MII)oocyte rate,cleavage rate,available embryo rate,high-quality embryo rate,biochemical pregnancy rate,clinical pregnancy rate,live birth rate,and miscarriage rate showed no significant differences(allP>0.05).In multivariable analysis,age,infertility duration,and progesterone level on the day of human chorionic gonadotropin(hCG)trigger were independent predictors of clinical pregnancy.Moreover,age and progesterone level on the hCG day were independently associated predictors of live birth(allP<0.05).Conclusions:Among women aged≥37 years,higher BMI did not significantly affect key laboratory or pregnancy outcomes after IVF/ICSI-ET.Clinical results were mainly influenced by age,infertility duration,and progesterone level on the hCG trigger day.
基金supported by the Research Foundation for the Clinical Project of Shanghai Municipal Health Commission(202140366)the“Science and Technology Innovation Action Plan”of the Basic Research Project of Shanghai Science and Technology Commission(23JC1403002)+2 种基金the Youth Research Initial Fund of Jinshan Hospital of Fudan University(JYQN-JC-202104)Medical Key Subjects of Jinshan District(JSZK2023H01)the Key Subject Development Project of Jinshan Hospital of Fudan University-Obstetrics and Gynecology(ZDXK-2023-6)。
文摘Objective:According to the previous studies,it has been found that long non-coding RNA H19(lncRNA H19)-ITGB3-miR-124-3p axis can regulate cell proliferation and invasion of the ectopic endometrium,which could be the potential pathway for treating endometriosis by a key medicine.The aim of this study was to investigate the roles of metformin,aspirin,artemisinin,and berberine in regulating the expression of lncRNA H19 in ectopic endometrial stromal cells(ecESCs)and explore novel medicines for the treatment of endometriosis.Methods:Isolation of ESCs from the ectopic endometrium of patients with endometriosis and treatment with metformin at 0.1 mmol/L,aspirin at 5.00 mmol/L,artemisinin at 20μmol/L,and berberine at 20μmol/L for 0,12,24,and 48 hours.LncRNA H19 levels in ecESCs after treatment were evaluated using real-time polymerase chain reaction,and changes in cell proliferation and invasion were determined using Cell Counting Kit-8 and Transwell assays.Results:lncRNA H19 levels in ecESCs in the metformin,aspirin,artemisinin,and berberine groups were significantly lower than those in the control group,with inhibition of cell proliferation and invasion;metformin and berberine showed the highest efficiency.Conclusions:Metformin and berberine inhibited ecESC proliferation and invasion by downregulating lncRNA-H19 levels,offering a novel treatment for endometriosis.
基金Health industry Clinical research Special/General project of Shanghai Health Commission(202240079)。
文摘Lichen sclerosus is a chronic inflammatory autoimmune skin disease that primarily affects the genital area, especially the vulva. It predominantly affects women and shows a bimodal incidence distribution. The principal clinical manifestations include vulvar itching, pain, and depigmentation, potentially leading to scarring, anatomical distortion, and malignant transformation if left untreated. The etiology is uncertain but may involve autoimmune factors, genetics, infections, hormones, trauma, chronic irritation, and oxidative stress. The diagnosis is primarily clinical, and histological confirmation is not always necessary when characteristic clinical signs are present. Although lichen sclerosus is incurable, it is manageable with appropriate treatment. This review summarizes the epidemiology, clinical features, complications, etiology, diagnosis, and treatment of lichen sclerosus.
文摘Objective:Cisplatin(CIS),as a common chemotherapy drug,induces detrimental effects on the testis.Besides,exosomes represent various beneficial effects,such as anti-inflammation and proliferation.In this experimental study,the authors aimed to evaluate the anti-inflammatory effects of circulating blood serum-derived exosomes on orchitis caused by CIS exposure.Methods:Male mice(n=18)were categorized into three main groups:control(no treatment),CIS(mice with orchitis caused by CIS injection),and CIS+exosome(orchitis-induced animals followed by exosome treatment).Exosomes were extracted from circulating blood,and orchitis was induced by intraperitoneal injection of CIS(7.5 mg/kg/day)for five consequence days.A day after the last dose of CIS,the exosome(10 IU/20 g mice)was injected intratesticularly.After a week,the samples,including blood serum and testis,were gathered.The levels of oxidative stress were assessed using malondialdehyde(MDA)and nitric oxide(NO)assays.Sperm parameters(morphology,viability,motility,and count),testosterone levels,and inflammatory(tumor necrosis factor-α[TNF-α],interleukin(IL)-6,and IL-10)gene expression were also evaluated.Histopathological and testicular apoptotic index(AI)were evaluated using hematoxylin and eosin(H&E)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)stainings,respectively.Finally,data analysis was applied by SPSS(v.19)software,andP<0.05 was considered as a significant level.Results:Following CIS administration,the sperm indices and testosterone levels were decreased(P<0.05);besides,NO,MDA,AI,and inflammatory gene expression were increased(P<0.05)in the CIS group compared to control animals.Following the prescription of exosomes in CIS animals,the sperm indices and testosterone levels were increased(P<0.05),and NO,MDA,AI,and inflammatory genes were decreased(P<0.05).Histopathological assessments also revealed disruption of seminiferous tubules and free from sperms following CIS administration.Also,the histological structure of damaged seminiferous tubules was changed to normal status following Exoxome prescription in CIS-exposure animals.Conclusion:Immediate intratesticular injection of blood-derived exosomes can alleviate orchitis CIS-exposed animals through anti-inflammatory features.
基金funded by NIH R01HD065939(co-funded by ORWH and NICHD)NIH R03HD097384NIH R03 HD100652 to X.Y.
文摘Objective: ATP6V0d2 is a subunit of the vacuolar-type H+-ATPase (V-ATPase) that pumps H+ ions into lysosomes. TRPML1 (MCOLN1/Mcoln1) transports cations out of lysosomes.Mcoln1^(-/-) mice recapitulate the lysosomal storage disorder mucolipidosis type IV (MLIV) phenotype. We previously demonstrated thatMcoln1^(-/-) female mice quickly became infertile at 5 months old (5M) with degenerating corpora lutea (CL) and progesterone (P4) deficiency. We tested our hypothesis thatAtp6v0d2 deficiency could partially compensate forMcoln1 deficiency to restore CL functions inAtp6v0d2^(-/-)Mcoln1^(-/-) mice.Methods: Control andAtp6v0d2^(-/-)Mcoln1^(-/-) female mice underwent fertility test from 2M to 7M. A subset of them was dissected at 5M on day 3.5 post-coitum (D3.5). The D3.5 ovaries from 5M control,Mcoln1^(-/-), andAtp6v0d2^(-/-)Mcoln1^(-/-) mice were evaluated for CL morphology, lipid droplet staining, and markers of mitochondria and P4 steroidogenesis in the luteal cells.Results: The fertility test ofAtp6v0d2^(-/-)Mcoln1^(-/-) female mice (2M–7M) revealed normal mating activity but reduced fertility compared with the control;yet ~25% of them remained fertile at 5M to 7M but with dystocia. We analyzed a subset of 11Atp6v0d2^(-/-)Mcoln1^(-/-) mice (5M) in the fertility test on D3.5: three (27.3%) had normal P4 levels and all examined CL parameters, indicating full restoration of CL function compared withMcoln1^(-/-), whereas eight had P4 deficiency, with two (18.2%) infertile and six (54.5%) once fertile. In contrast toMcoln1^(-/-) CLs, which had extensive amorphous cellular debris, indicating cell degeneration,Atp6v0d2^(-/-)Mcoln1^(-/-) CLs had reduced amorphous cellular debris regardless of P4 levels. However, similar toMcoln1^(-/-) CLs, P4-deficientAtp6v0d2^(-/-)Mcoln1^(-/-) CLs showed impaired differentiation, enlarged lipid droplets, disorganized expression of endothelial basal lamina marker collagen IV, and reduced expression of mitochondrial marker heat shock protein 60 (HSP60) and steroidogenesis rate-limiting protein StAR, indicating that additionalAtp6v0d2 deficiency compensates forMcoln1 deficiency-induced cell degeneration, but is insufficient to restore luteal cell differentiation and P4 steroidogenesis in P4-deficientAtp6v0d2^(-/-)Mcoln1^(-/-) CLs.Conclusion: This study shows thatAtp6v0d2^(-/-)Mcoln1^(-/-) CLs had varied improvements compared withMcoln1^(-/-) CLs, and it providesin vivo genetic evidence of the coordination between different lysosomal channels in CL function.
基金Immunogenetic Research Center(IRC)of Sari Medical Faculty and Chancellor for Research and Technology of Mazandaran University of Medical Sciences(93-1997)。
文摘Objective:Cyclophosphamide(CP)is an anticancer drug that induces oxidative stress,leading to gonadal toxicity.This study aimed to evaluate the effectiveness of co-treatment with zinc oxide nanoparticles(nZno)and melatonin(Mel)on lipid peroxidation and antioxidant enzyme levels against CP-induced testicular damage.Methods:In this study,42 adult male rats were divided into six groups.The control group received intraperitoneal(i.p.)saline solution.The CP group was administered CP at 60 mg/kg/week.The Mel+CP and nZno+CP groups received CP along with 10 mg/kg Mel and 5 mg/kg nZno,respectively.The Mel+nZno+CP group received CP plus 10 mg/kg Mel and 5 mg/kg nZno,simultaneously.The Mel+nZno group received 10 mg/kg Mel and 5 mg/kg nZno simultaneously.Eight weeks after the treatment,hormonal assays,total antioxidant capacity(TAC),histological studies,lipid peroxidation levels,and antioxidant enzyme status were assessed.Results:Biochemical results showed that CP decreased spermatogenic lineage cells,TAC,levels of antioxidant enzymes catalase(CAT),glutathione(GSH),and glutathione peroxidase(GSH-Px),and reproductive hormone levels luteinizing hormone(LH),follicle-stimulating hormone(FSH)and testosterone,and increased malondialdehyde(MDA)content.In contrast,co-treatment with Mel and nZno in the Mel+nZno+CP group resulted in a significant improvement in all examined parameters(P<0.05).Conclusion:The results indicate that the simultaneous administration of Mel and nZno could be used as a potential protective agent against CP-induced reproductive toxicity.
文摘Objective:To analyze the clinical characteristics,diagnostic challenges,treatment strategies,and long-term outcomes of ovarian leiomyomas through a 20-year retrospective study,aiming to improve awareness and management of this rare tumor.Methods:This single-center retrospective study included 39 cases of ovarian leiomyomas confirmed by histopathology and immunohistochemistry between January 2003 and December 2023 at the Obstetrics and Gynecology Hospital affiliated with Fudan University.Clinical,imaging,surgical,and follow-up data were systematically reviewed.Pathological criteria,including mitotic index and immunohistochemical markers,were used for tumor classification.Results:Among the 39 patients,10 were diagnosed with primary ovarian leiomyomas and 29 with secondary forms.The average age was 52.3 years,and most tumors were unilateral and incidentally discovered.Clinical symptoms included abdominal pain,distension,and abnormal uterine bleeding,while 66.7%of patients were asymptomatic.Imaging via ultrasound revealed solid or hypoechoic masses,but lacked specificity.MRI was used in only three cases.Histologically,tumors showed well-differentiated smooth muscle cells with low mitotic activity.Immunohistochemical staining confirmed smooth muscle origin.All patients underwent surgical excision.No recurrences were observed during a median follow-up of 12 years.Conclusion:Ovarian leiomyomas are rare and often asymptomatic,leading to frequent misdiagnosis.Accurate diagnosis relies on histopathology and immunohistochemistry.Surgical resection offers excellent outcomes,and ovary-sparing approaches should be considered in younger patients.Greater clinical awareness and additional research are essential to improve diagnostic accuracy and therapeutic strategies.
基金Ministry of Science and Technology of China(2020YFC2002800,2020YFC2002803)。
文摘Objective:To evaluate the clinical efficacy of vaginal repair as a salvage treatment for cesarean scar defects in patients with previously failed repair surgery.Methods:This retrospective cohort study included 16 patients with cesarean scar defects who underwent vaginal repair as salvage therapy after prior repair surgery failure between March 2019 and September 2022 at the Department of Obstetrics and Gynecology,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine.The previous failed procedures included vaginal repair,hysteroscopic repair,and laparoscopic repair.A control group of 108 patients who underwent primary vaginal repair during the same period was also analyzed.Perioperative outcomes and post-operative repair efficacy were compared.The length,width,and depth of the cesarean scar defect,as well as the thickness of the residual myometrium,were measured by transvaginal ultrasonography.Results:No significant differences were observed between the two groups in demographic characteristics.In both groups,the duration of menstruation significantly decreased after vaginal repair(from 12.8±5.3 to 6.75±1.8 days in the salvage therapy group,and from 13.5±3.8 to 7.1±1.7 days in the primary surgery group),while the thickness of the residual myometrium significantly increased(from 3.0±2.0 to 7.7±2.6 mm in the salvage therapy group,and from 2.6±1.2 to 7.7±2.5 mm in the primary surgery group).Post-operatively,there were no significant differences between the two groups in either menstrual duration(6.8±1.8vs.7.1±1.7 days)or residual myometrial thickness(7.7±2.6vs.7.7±2.5 mm).The data also indicated that performing salvage therapy within≤21 months of the initial surgery was associated with a better prognosis.Conclusions:Vaginal repair as salvage therapy is a feasible and effective option for patients with cesarean scar defects after failed repair surgery.
文摘Recent progress inin vitro maturation(IVM)technology using human immature oocytes for clinical applications has been reported.The success rate of IVM technology depends on the source of immature oocytes,and to date,no single protocol has demonstrated superior results over others.Attempts to adapt IVM protocols developed in animal models have not let to significant breakthroughs in culture conditions and systems.Cumulus cells are known to play an important role in oocyte maturation;however,the results of co-culture with different types of cells for IVM of human immature oocytes remain controversial.As one of the assisted reproductive technologies(ART),IVM is only involved in a specific procedure for infertility treatment and fertility preservation.With the development of IVM technology,it has been proposed that the combination of mild-stimulation cycle with retrieval of both mature and immature oocytes,followed by IVM,may offer a viable alternative to the conventional stimulation cycle treatment.
文摘Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring.Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group;Group 2, the IG group, in which utrogestan was administeredvia intragastric gavage;Group 3, the IM group, in which P4 was administeredvia intramuscular injection;and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis.Results: No significant alterations in fertility outcomes were observed through three P4 administration routes-intragastric gavage, intramuscular injection, and vaginal administration-in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatmentvia the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereasOlivella appeared exclusively in the control group rather than in the P4 treatment groups.Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.
基金supported by the National Key Research and Development Program of China(2021YFC2700701,2022YFC2703803,and 2022YFC2703001)the National Natural Science Foundation of China(82088102,82071731,82171613,8227034,and 81601238)+9 种基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-064)the Science and Technology Commission of Shanghai Municipality(21Y11907600)Shanghai Municipal Commission of Health and Family Planning(20215Y0216)Collaborative Innovation Program of Shanghai Municipal Health Commission(2020CXJQ01)Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1008A)Shanghai Clinical Research Center for Gynecological Diseases(22MC1940200)Shanghai Urogenital System Diseases Research Center(2022ZZ01012)Shanghai Frontiers Science Research Base of Reproduction and Development,The Science and Technology Commission of Quzhou Municipality(2022K54)Open Fund Project of Key Laboratory of Reproductive Genetics,Ministry of Education,Zhejiang University(KY2022035)Open Fund Project of Guangdong Academy of Medical Sciences(YKY-KF202202).
文摘Objective:This study aimed to investigate the influence of lung function on the relationship between allergies and hypertension,thereby elucidating significant potential mechanisms from a genetic standpoint.We investigated the causal relationship between childhood allergies(age<16 years)and essential hypertension and identified and quantified the role of lung function(forced vital capacity[FVC]and forced expiratory volume in the first second/forced vital capacity[FEV1/FVC])as potential mediators.Methods:Using data from a genome-wide association study and the Fenn Genn consortium,a two-sample Mendelian randomization(MR)analysis of genetically predicted childhood allergies(7128 cases and 211,703 controls)and essential hypertension(116,714 cases and 1,032,659 controls)was performed.Furthermore,we used two-step MR to quantify the effect of lung function-mediated childhood allergies on essential hypertension.The FVC and FEV1/FV sample size was 371,898.Results:Childhood allergies were associated with increased odds of developing essential hypertension(odds ratio[OR]=1.0900,95%confidence interval[CI]=1.0034–1.1842,P=0.0414).No strong evidence that genetically predicted essential hypertension affected childhood allergy risk was identified(OR=1.0631,95%CI=0.9829–1.1498,P=0.1264).The proportion of genetically predicted childhood allergies mediated only by FVC was 5.67%(95%CI,5.13%–5.73%).Conclusion:A causal relationship between childhood allergies and essential hypertension was identified,with a proportion of the effect mediated by FVC.Therefore,implementing early interventions in children with allergies is imperative to mitigate the long-term risk of developing hypertension.Further research is required to identify additional risk factors as potential mediators.
文摘Objective:Endometriosis is a chronic gynecological disease requiring relatively long therapy of at least 3 to 6 months,and has a high recurrence rate.Further research using animal models is needed to better understand the disease.During the COVID-19 pandemic,laparoscopic surgeries were suspended to minimize infection risk.This study aims to establish an experimental animal model of endometriosis using stored chocolate cyst pulp.Methods:This laboratory experimental study included 12 female Mus musculus mice.Immunodeficient mice were intraperitoneally injected with a previously prepared chocolate cyst slurry.On the 15th day,the mice were euthanized,and anatomical pathological examination was performed using hematoxylin and eosin(HE)staining.Results:Anatomical pathology examination revealed stromatosis in the fat tissue of all 12 mice treated with stored chocolate cyst slurry,confirming the presence of endometriosis.The protocol demonstrated a 100%success rate in developing a mouse model of endometriosis.Conclusion:The successful development of a mouse endometriosis model from stored chocolate cyst slurry using this protocol is expected to contribute to experimental animal studies.
基金partially supported by a grant from the Quzhou Municipal Bureau of Science and Technology of Zhejiang Province,China(2021Y012)。
文摘Polycystic ovary syndrome(PCOS)is a common gynecological disease that affects women of reproductive age and is characterized by hyperandrogenism,ovulatory dysfunction,and polycystic changes in the ovaries.In recent years,along with irregular menstruation and infertility,metabolic abnormalities associated with PCOS have garnered increasing attention.Insulin resistance is the most prevalent metabolic abnormality in patients with PCOS and is closely related to disease progression and severity.Insulin-sensitizing drugs improve obesity-and hyperinsulinemia-related symptoms in patients with PCOS.Although the exact etiology of PCOS remains incompletely understood,genomic and metabolomic studies have identified various metabolic changes in the serum and follicular fluid of patients with PCOS and in animal models.These findings shed light on the pathogenesis of PCOS and help identify new preventive and therapeutic approaches.This review explores the role of insulin resistance in the pathophysiology of PCOS,focusing on its effects on ovulation and hyperandrogenism.It also summarizes recent therapeutic advancements,evaluates their efficacy,and discusses strategies for the long-term management of insulin resistance in PCOS.
基金Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(YGLX202311)Clinical Incubation Project of Beijing Chao-Yang Hospital(CYFH202307)。
文摘Objective:To study the effects of preconceptional thyroid-stimulating hormone(TSH)levels on antral follicle count(AFC)and pregnancy outcomes in a firstin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)cycle.Methods:A retrospective cohort study was conducted to explore the effects of preconceptional TSH levels on AFC and pregnancy outcomes in 1340 patients.The patients were divided into three groups:group 1,0.55≤TSH<2.5μIU/mL(n=868);group 2,2.5≤TSH<4.0μIU/mL(n=334);and group 3,TSH≥4.0μIU/mL(n=138).Results:There were significant differences in AFC(P=0.002),number of zygotes(P=0.008),and fertilization rate(P=0.015)among the three groups.Among the three groups,there were no obvious differences in live birth(P=0.559),high-quality embryo(P=0.108),or clinical pregnancy(P=0.939)rates.Binary logistics regression analysis showed that TSH correlated with AFC when TSH was≥4μIU/mL(P=0.033);however,TSH levels had no effect on live birth or clinical pregnancy rate.Conclusions:Although the preconceptional TSH level negatively related with AFC,number of zygotes,and fertility rate,especially when TSH was>4μIU/mL,TSH was not an independent factor on the live birth rate among fertile women undergoing their first IVF/ICSI-embryo transfer treatment.The effect of TSH levels on couples undergoing assisted reproductive technology requires further investigation.
基金National Natural Science Foundation of China(82273233)Natural Science Foundation of Shanghai(22ZR1408900)Clinical Research Plan of SHDC(SHDC2020CR4079)。
文摘Quality control in disease diagnosis and treatment is critical for ensuring patient safety,optimizing resource utilization,and improving clinical outcomes.In endometrial cancer management,rigorous quality control ensures accurate diagnosis through standardized protocols,reducing misdiagnosis and enabling early detection.Treatment is guided by evidence-based guidelines,fostering multi-disciplinary collaboration and minimizing unnecessary variations in care.Quality control also enhances patient safety by reducing medical errors and ensuring compliance with ethical and legal standards.By fostering transparency,professional development,and patient-centered care,it supports the sustainable advancement of healthcare systems,ultimately improving outcomes for patients and the broader medical community.This quality control of endometrial cancer was drafted by the Obstetrics and Gynecology Hospital of Fudan University based on the American Joint Committee on Cancer’s TNM staging(AJCC,8th edition,2017)and the International Federation of Obstetrics and Gynecology’s surgical pathological staging(FIGO,2009).
基金National Key Research and Development Program of China(2021YFC2700700,2022YFC2703500)National Natural Science Foundation of China(82171686)+4 种基金Clinical Research Program of Shanghai Municipal Health Commission(202340222)Natural Science Foundation of Shanghai(20ZR1463100)Clinical Research Plan of Shanghai Shenkang Hospital Development Center(SHDC2023CRD001)Shanghai Clinical Research Center for Gynecological Diseases(22MC1940200)Shanghai Urogenital System Diseases Research Center(2022ZZ01012)。
文摘Objective:Frozen-thawed embryo transfer(FET)is widely used inin vitro fertilization(IVF)clinics but is associated with an increased risk of several pregnancy complications,including large-for-gestational age and placenta-related diseases.However,the effects of FET on placentation remain unclear.Therefore,we used single-cell RNA-sequencing(scRNA-seq)technology to investigate the impact of FET on placental gene expression in different subtypes of trophoblasts.Methods:A mouse model of IVF and FET was constructed to collect placenta tissues.scRNA-seq was performed on placentas from two dams undergoing IVF-embryo transfer and two dams undergoing IVF-FET.Differentially expressed gene(DEG)analyses were performed in different subtypes of trophoblasts.Identified DEGs were polymerase chain reaction(PCR)validated.Results:The fetal weights and placental efficiency were higher in the FET group than those in the IVF group at E18.5,with no significant difference in placental weights.Subsequently,55,406 placental cells were captured and annotated.Upregulated DEGs in the FET group in syncytiotrophoblasts(SynTs)and sinusoidal trophoblast giant cells(S-TGCs)within the placental labyrinth were enriched in pathways related to vascular development and oxidative stress,respectively.The expression of the imprinted geneIgf2 in SynTs,S-TGCs,and spongiotrophoblasts was significantly increased.In the junctional zone,FET upregulated the expression of prolactin genes such asPrl3b1 in glycogen trophoblasts(GlyTs)while the downregulated expression of GlyT genes following FET was associated with mesenchyme development.Conclusions:This study first identifies DEGs and enriched pathways in different subtypes of trophoblasts following FET.These genes and pathways may contribute to the increased placental efficiency and fetal weights.Future studies are required to confirm these results and further explore the key mechanisms in placental pathologies.
基金supported by the National Natural Science Foundation of China(81971456)to X.Q.W.National Natural Science Foundation of China(32070915)to D.J.L.National Key Basic Research Project(2015CB943300)to D.J.L.
文摘Despite impressive progress being made in investigating the mechanisms underlying endometriosis,the pathophysiology of this disease remains unclear.Although typical methods used for diagnosing endometriosis such as ultrasound,magnetic resonance imaging,and blood tests are available,these are also inefficient,and effective noninvasive diagnostic methods are lacking.The advances in high-throughput omics techniques have enabled metabolomics to become an effective approach for discovering promising biomarkers.The aberrant metabolism associated with serious symptoms of endometriosis in women has been revealed in recent years.Analyzing the global metabolic patterns in patients with endometriosis may help deepen the understanding of the disease mechanism and have a significant impact on future diagnostic and treatment methods for endometriosis.Herein,we reviewed relevant studies on metabolic changes in patients with endometriosis and discussed the changes in metabolites both in biological fluids and endometriosis tissues.The findings discussed in this review have potential diagnostic implications and will enhance the understanding of the pathophysiological processes underlying the disease.
基金National Natural Science Foundation of China(82071598)。
文摘Objective:To determine the presence of female germline stem cells(FGSCs)in postnatal mammals under physiological and pathological conditions.Methods:We explored the presence of FGSCs using various models,including mice of different ages,an ovarian mouse model with mechanical injury,and a rat model of endometriosis.Moreover,we investigated the feasibility of inducing FGSCs in vitro using cultured ovarian tissues and employed the differential adhesion method for isolating FGSCs.For labeling FGSCs within the ovary,we employed markers such as mouse VASA homolog(MVH)/ubiquitin carboxy-terminal hydrolase L1(UCHL1)and 5-Bromo-2'-deoxyuridine(BrdU).Results:Our investigations revealed that FGSCs were not detectable in any of our models,across all conditions tested.Conclusion:Our experiments provide evidence for the viewpoint that no FGSC exists in the ovaries of postnatal mice or rats,and then support that mammalian ovaries do not produce new oocytes after birth.
