The pathogenesis and therapeutic treatment of intrauterine adhesions （IUAs） remain unsolved, highlighting the need for stable and effective experimental animal models. In this study, uterine electrocoagulaUon of twe...The pathogenesis and therapeutic treatment of intrauterine adhesions （IUAs） remain unsolved, highlighting the need for stable and effective experimental animal models. In this study, uterine electrocoagulaUon of twenty-one female New Zealand White rabbits was carried out to establish an IUA model. As rabbits have two completely separate uterine horns, each rabbit had its own internal control： one uterine horn was given an electrothermal injury （Group A, n=21）, and the contralateral uterine horn received no treatment and served as the control （Group B, n=21）. The en- dometrial morphology, number of endometrial glands, area of endometrial fibrosis, and number of implanted fetuses were compared between the two groups. In Group A, the numbers of endometrial glands on Days 7 and 14 and the number of implanted fetuses were significantly lower than those in Group B（P〈0.05, P〈0.05, and P〈0.01, respectively）, while the ratio of the area with endometrial stromal fibrosis to the total endometrial area was significantly increased （P〈0.01）. These results suggest that this method of electrothermal injury is effective for the establishment of a rabbit lUA model between 7 and 14 d after surgery.展开更多
Balanced reciprocal translocation is one of the most common chromosome abnormalities,with an incidence of approximately 1in every 500 newborns(Mackie Ogilvie and Scriven,2002).Most balanced reciprocal translocation ca...Balanced reciprocal translocation is one of the most common chromosome abnormalities,with an incidence of approximately 1in every 500 newborns(Mackie Ogilvie and Scriven,2002).Most balanced reciprocal translocation carriers have no observable phenotype because there is no loss or gain of genetic material(Ogilvie et al.,2001).However,the carriers have a risk of infertility.展开更多
The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ova...The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA).Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups:control group,PCOS group,and PCOS with high-fat diet (HFD) group.Serum hormones were assayed by radioimmunoassay (RIA).The ovaries'were immunohistochemically stained with MIF,and the expression of MIF,p-JNK and p-p38 was detected by Western blotting in ovaries.The serum testosterone level,LH concentration,LH/FSH ratio,fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478,13.809±1.701,1.820±0.404,10.83±1.123 and 1.8692±0.1096)and PCOS with HFD group (6.075±0.439,14.075±1.927,1.779±0.277,10.20±1.377 and 1.7736±0.6851)were significantly higher than those in the control group (4.949±0.337, 2.458±0.509,1.239±0.038,9.53±0.548 and 1.5329±0.7363),but there was no significant difference between the PCOS group and PCOS with HFD group.The expression levels of MIF,p-JNK,and p-p38 in the PCOS group (0.4048±0.013,0.6233±0.093 and 0.7987±0.061)and PCOS withHFD group (0.1929±0.012,0.3346±0.103 and 0.3468±0.031)were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061),but no Significant difference was observed between PCOS group and PCOS with HFD group.It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.展开更多
Semen from 5210 sperm bank donors was analyzed and trends in semen quality were evaluated at Shandong Human Sperm Bank between 2008 and 2014. After 2-7 days of abstinence, semen samples were collected. Measurements of...Semen from 5210 sperm bank donors was analyzed and trends in semen quality were evaluated at Shandong Human Sperm Bank between 2008 and 2014. After 2-7 days of abstinence, semen samples were collected. Measurements of semen volume, sperm concentration, sperm forward motility, and total sperm count were performed. There were significant declining trends in semen volume, sperm concentration, sperm forward motility, and total sperm count. Our results indicate that the quality of semen in this cohort of sperm donors had decreased during the study period.展开更多
Antisperm antibodies(ASAs)are assumed to be a possible causative factor for male infertility,with ASAs detected in 5%-15%of infertile men but in only l%-2%of fertile ones.It remains unclear whether ASAs have an advers...Antisperm antibodies(ASAs)are assumed to be a possible causative factor for male infertility,with ASAs detected in 5%-15%of infertile men but in only l%-2%of fertile ones.It remains unclear whether ASAs have an adverse effect on the outcome of in v/tro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).This study investigated differences in the rates of fertilization,pregnancy,and live births associated with serum ASA-positive and ASA-negative men following IVF or ICSI.Five hundred and fifty-four consecutive infertile couples undergoing IVF(n=399)or ICSI(n=155)were included.The two-sample two-sided t-test and Chi-square or Fisher's exact test was used for statistical analysis.Lower rates of fertilization(41.7%vs 54.8%,P=0.03),good embryos(18.9%vs 35.2%,P=0.00),pregnancy(38.5%vs 59.4%,P=0.00),and live births(25.8%vs 42.5%,P=0.00)were observed in men of the IVF group with a positive serum ASA than in those with a negative ASA.ASA positivity/negativity correlated with pregnancy rates(P=0.021,odds ratio[OR]:0.630,95%confidence interval[Cl]:0.425-0.932)and live birth rates(P=0.010,OR:1.409,95%Cl:1.084-1.831)after controlling for the female serum follicle-stimulating hormone level and the couple's ages at IVF.Women coupled with ASA-positive men had lower live birth rates with IVF than with ICSI(25.8%and 47.4%,respectively;P=0.07).Women coupled with ASA-positive men had lower rates of pregnancy and live births following IVF than those coupled with ASA-negative men but had a similar outcome with ICSI.展开更多
This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol （PPOS） in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-c...This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol （PPOS） in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn＇t get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol （non-PPOS group）, and underwent PPOS protocol （PPOS group） in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University. The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer （FET） in PPOS group, and good-quality embryo rate in both groups. The secondary outcomes were fertilization rate, egg utilization rate and cycle cancellation rate. The results showed that there were no significant differences in basal follicle stimulating hormone （bFSH）, antral follicle count （AFC）, duration and total dosage of gonadotropin （Gn）, number of oocytes retrieved, intracytoplasmic sperm injection （ICSI） rate, fertilization rate, and cycle cancellation rate between the two groups （P〉0.05）. However, the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group （P〈0.05）. By the end of April 2017, 62 FET cycles were conducted in PPOS group. The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%, respectively. In conclusion, PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ ICSI-ET cycles.展开更多
There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and...There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del(p.D51fs)frame-shift mutation in exon 3 of the testis expressed 11(TEX11)gene in one patient.Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation.Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes.In contrast,testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression.Western blotting of human embryonic kidney(HEK293)cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression.In conclusion,we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient,emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.展开更多
The purpose of this study was to determine the diagnostic accuracy of serum inhibin B(INHB)as a predictor of the retrieval outcome of testicular haploid gametes(spermatids and testicular spermatozoa)in nonobstructive ...The purpose of this study was to determine the diagnostic accuracy of serum inhibin B(INHB)as a predictor of the retrieval outcome of testicular haploid gametes(spermatids and testicular spermatozoa)in nonobstructive azoospermic men.Serum hormone levels,testicular volume,and histological evaluation were performed in 403 Chin ese non obstructive azoospermic men.Testicular haploid gamete was successfully retrieved in 213 of 403 patients(52.85%).The haploid gamete group always had higher INHB levels than the non-haploid gamete group.According to the receiver operating characteristic(ROC)curve analysis,INHB was a good predictor of testicular haploid gamete retrieval outcome in all patients(sensitivity:77.93%and specificity:91.58%)and patients with normal follicle-stimulating hormone(FSH;sensitivity:88.52%and specificity:70.83%).The area under the ROC curve(AUC)of INHB was similar to that of FSH in all patients or patients with normal FSH.In patients with elevated FSH,INHB was superior to FSH in predicting the presence of haploid gamete(AUC:0.73 vs 0.55,P<0.05),with a sensitivity of 60.00%and a specificity of 80.28%.It con eluded that serum INHB as an effective marker for spermatoge nesis was a sign ificant predictor of testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men.Especially,INHB is superior to FSH in predicting the presenee of haploid gamete in the patients with elevated FSH.展开更多
We aim to investigate the correlations between hemodynamic parameters, penile rigidity grading, and the therapeutic effects of phosphodiesterase type 5 inhibitors using color Doppler flow imaging after intracavernosal...We aim to investigate the correlations between hemodynamic parameters, penile rigidity grading, and the therapeutic effects of phosphodiesterase type 5 inhibitors using color Doppler flow imaging after intracavernosal injection in patients with erectile dysfunction. This study involved 164 patients. After intracavernosal injection with a mixture of papaverine （60 mg）, prostaglandin E1 （10 μg）, and lidocaine （2%, 0.5-1 ml）, the penile vessels were assessed using color Doppler flow imaging. Penile rigidity was classified based on the Erection Hardness Score system as Grades 4, 3, 2 or 1 （corresponding to Schramek Grades Ⅴ to Ⅱ）. Then, the patients were given oral sildenafil （50-100 mg） and scored according to the International Index of Erectile Function （IIEF-5） questionnaire. The number of patients with penile rigidities of Schramek Grades Ⅱ to Ⅴ was 14, 18, 21, and 111, respectively. The IIEF-5 score was positively correlated with the refilling index of the penile cavernosal artery （r = 0.79, P 〈 0.05）, the peak systolic velocity （r= 0.45, P〈 0.05）, and penile rigidity （r= 0.75, P〈 0.05）, and was negatively correlated with the end diastolic velocity （r = -0.74, P 〈 0.05）. For patients with erectile dysfunction, both the IIEF-5 score after sildenafil administration, which is correlated with penile rigidity, and the hemodynamic parameters detected using color Doppler flow imaging may predict the effects of phosphodiesterase type 5 inhibitor treatment and could provide a reasonable model for the targeted-treatment of erectile dysfunction.展开更多
Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segre...Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segregation and promote genetic diversity of progenies.Crossover patterns are tightly controlled and exhibit three characteristics:obligatory crossover,crossover interference,and crossover homeostasis.Aberrant crossover patterns are the leading cause of infertility,miscarriage,and congenital disease.Crossover recombination occurs in the context of meiotic chromosomes,and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally.Meiotic chromosomes are organized in a loop-axis architecture.Diverse evidence shows that chromosome axis length determines crossover frequency.Interestingly,short chromosomes show different crossover patterns compared to long chromosomes.A high frequency of human embryos are aneuploid,primarily derived from female meiosis errors.Dramatically increased aneuploidy in older women is the well-known“maternal age effect.”However,a high frequency of aneuploidy also occurs in young women,derived from crossover maturation inefficiency in human females.In addition,frequency of human aneuploidy also shows other age-dependent alterations.Here,current advances in the understanding of these issues are reviewed,regulation of crossover patterns by meiotic chromosomes are discussed,and issues that remain to be investigated are suggested.展开更多
The impact of prior cesarean section（CS） on the pregnancy and neonatal outcomes of in vitro fertilization and embryo transfer（IVF-ET） was investigated. A retrospective analysis was performed on 144 patients with p...The impact of prior cesarean section（CS） on the pregnancy and neonatal outcomes of in vitro fertilization and embryo transfer（IVF-ET） was investigated. A retrospective analysis was performed on 144 patients with prior CS between January 2013 and December 2015. The pregnancy, delivery, and neonatal outcomes of patients who had previous CS delivery and received IVF-ET were analyzed. The control group comprised 166 patients who had only previous vaginal delivery（VD） and received IVF-ET during the same period. The results showed that the basal follicle stimulating hormone level, estradiol level on human chorionic gonadotropin（h CG） day, gonadotrophin dosage, duration of stimulation, retrieved oocytes, fertilization rate, high-quality embryo rate, multiple birth rate, abortion rate and ectopic pregnancy rate had no significant difference between the two groups（P〉0.05）. The pregnancy rate（40.28% vs. 54.22%） and implantation rate（24.01% vs. 34.67%） were significantly lower（P〈0.05）, and the ratio of embryo difficulty transfer（9/144 vs. 0/166） was significantly higher in CS group than in VD group. The risk of pernicious placenta previa and postpartum hemorrhage in twin deliveries was significantly increased in CS group as compared with that in VD group（P〈0.05）, and gestational age and neonatal birth weight were significantly reduced in twin deliveries as compared with singleton deliveries in both groups（P〈0.05）. It was suggested that the existence of CS scar may impact embryo implantation and clinical pregnancy outcome, and increase the difficulty of ET. We should limit the number of transfer embryos to avoid multiple pregnancies and strengthen gestational supervision in patients with cesarean scar.展开更多
Testicular sperm extraction is a common procedure used to find spermatogenic cells in men with nonobstructive azoospermia. The laboratory processing of biopsied testicular tissues needs to be performed meticulously to...Testicular sperm extraction is a common procedure used to find spermatogenic cells in men with nonobstructive azoospermia. The laboratory processing of biopsied testicular tissues needs to be performed meticulously to acquire a high yield of cells. In this study, the effectiveness of mincing the tissues after testicular biopsy was assessed using histological evaluation, as was the possible adverse effect of residual tissue on the migration of spermatogenic cells during density gradient centrifugation. Our results indicate that testicular residual tissue, when laid on the density gradient medium along with the sperm wash, hinders the spermatogenic cells＇ forming a pellet during centrifugation, and therefore impairs the intracytoplasmic sperm injection procedure. Whereas the mean number of recovered cells from the sperm wash medium （SWM） with residual tissue is 39.435 ~ 24.849, it was notably higher （60.189 ~ 28.214 cells） in the SWM without minced tissues. The remaining tissue contained no functional seminiferous tubules or spermatogenic cells in histological sections. In conclusion, the remaining residual tissue after mincing biopsied testicular tissue does not add any functional or cellular contribution to spermatogenic cell retrieval; in fact, it may block the cellular elements in the accompanying cell suspension from migrating through the gradient layers to form a pellet during centrifugation and cause loss of spermatogenic cells.展开更多
Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target...Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.展开更多
This study aimed to evaluate fertility and onco-logic outcomes in women with complex hyperplasia(CH)or complex atypical hyperplasia(CAH)who received fertility-sparing therapy and in vitro fertili-zation(IVF).Endometri...This study aimed to evaluate fertility and onco-logic outcomes in women with complex hyperplasia(CH)or complex atypical hyperplasia(CAH)who received fertility-sparing therapy and in vitro fertili-zation(IVF).Endometrial carcinoma is the most common carcinoma of the female genital tract(Stu-bert and Gerber,2016),and is associated with endo-metrial hyperplasia(EH)resulting from long-term unopposed estrogenic stimulation of the endometrium.EH is characterized by non-physiological prolifera-tion of endometrium that results in glands with ir-regular shapes and varying sizes(Horn et al.,2007).The World Health Organization(WHO)classified it into four types:simple or complex hyperplasia with or without atypia.CH is characterized by glands with irregular outlines that demonstrate marked structural complexity and back-to-back crowding.Atypical hyperplasia designates a proliferation of glands ex-hibiting cytologic atypia,in which varying degrees of nuclear atypia and loss of polarity are present(Kur-man et al.,1985).It has been reported that high-dose progestin is safe and efficient for CAH or early-stage low-grade carcinoma for young women who desire fertility-preserving treatment(Randall and Kurman,1997).However,few studies have reported the dif-ferences of pregnancy outcomes between patients with CAH and CH,while those patients take a great proportion in people suffered from infertility.More studies about the outcome of IVF are needed.Our aim is to evaluate fertility and oncological outcomes in women with CH or CAH who received fertility-sparing therapy.展开更多
Dear Editor, Klinefelter syndrome （KS） is the most frequent genetic cause of infertility in men. Paternity can be achieved through intracytoplasmic sperm injection （ICSI） with spermatozoa recovered from ejaculated...Dear Editor, Klinefelter syndrome （KS） is the most frequent genetic cause of infertility in men. Paternity can be achieved through intracytoplasmic sperm injection （ICSI） with spermatozoa recovered from ejaculated semen if exist, or testes with testicular sperm extraction （TESE）.展开更多
In this study,we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection on semenparameters.The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection fr...In this study,we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection on semenparameters.The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank ofthe Center for Reproductive Medicine,Shandong University(Jinan,China).The volunteers had normal sperm concentration beforeinfection.Each volunteer provided semen samples before and after infection.We selected 90 days after infection as the cutoff point.Semen parameters within 90 days after infection of 109 volunteers(group A)were compared with semen parameters before infection.Moreover,semen parameters on or after 90 days after infection of 36 volunteers(group B)were compared with semen parameters beforeinfection.Furthermore,based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster,volunteersin group A and B were further divided into two subgroups separately.Semen parameters were compared before and after infection ineach subgroup.Our results showed that in this cohort population,the semen quality in volunteers with normal sperm concentrationsbefore infection decreased after SARS-CoV-2 infection within 90 days,while the semen quality returned to preinfection levels after 90days.The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.展开更多
Non-obstructive azoospermia(NOA),the lack of sperm in the ejaculate due to failure of spermatogenesis,can result from a variety of diverse factors,with genetic factors accounting for~30%of NOA cases,including chromoso...Non-obstructive azoospermia(NOA),the lack of sperm in the ejaculate due to failure of spermatogenesis,can result from a variety of diverse factors,with genetic factors accounting for~30%of NOA cases,including chromosomal aberrations,Y-chromosome microdeletions,and monogenic variants(Tang et al.,2022).More than 2000genes are known to participate in spermatogenesis,and>400 genes specifically linked to azoospermia have been identified through studies in mouse models(Krausz and Riera-Escamilla,2018).However,relatively few genes associated with azoospermia in mice have been verified in humans.展开更多
E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respective...E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.展开更多
The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration ...The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone（FSH） on follicular growth and granulosa cell gonadotropin receptor m RNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages（days 1–7）,but inhibited at later stage（days 7–14） of in vitro culture. Interestingly,testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH（400 m IU/m L）. In addition,in cultured granulosa cells,high testosterone concentrations induced cell proliferation,and increased the m RNA expression level of FSH receptor（FSHR）,and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development,most likely through regulation of the FSH signaling pathway,although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.展开更多
To the Editor:Septate uterus is the most common congenital uterine malformation associated with an increased risk of miscarriage,preterm birth,and fetal malpresentation and reduced clinical pregnancy rates.The Europea...To the Editor:Septate uterus is the most common congenital uterine malformation associated with an increased risk of miscarriage,preterm birth,and fetal malpresentation and reduced clinical pregnancy rates.The European classification defines septate uterus as having an internal fundal indentation exceeding 50%of the uterine wall thickness and an external indentation less than 50%of the uterine wall thickness.展开更多
基金Project supported by the Key Research and Development Program of Shandong Province(No.2015GSF118124)the Projects of Medical and Health Technology Development Program in Shandong Province(No.2016WS0369)the National Research and Development Plan(No.2016YFC1000600),China
文摘The pathogenesis and therapeutic treatment of intrauterine adhesions （IUAs） remain unsolved, highlighting the need for stable and effective experimental animal models. In this study, uterine electrocoagulaUon of twenty-one female New Zealand White rabbits was carried out to establish an IUA model. As rabbits have two completely separate uterine horns, each rabbit had its own internal control： one uterine horn was given an electrothermal injury （Group A, n=21）, and the contralateral uterine horn received no treatment and served as the control （Group B, n=21）. The en- dometrial morphology, number of endometrial glands, area of endometrial fibrosis, and number of implanted fetuses were compared between the two groups. In Group A, the numbers of endometrial glands on Days 7 and 14 and the number of implanted fetuses were significantly lower than those in Group B（P〈0.05, P〈0.05, and P〈0.01, respectively）, while the ratio of the area with endometrial stromal fibrosis to the total endometrial area was significantly increased （P〈0.01）. These results suggest that this method of electrothermal injury is effective for the establishment of a rabbit lUA model between 7 and 14 d after surgery.
基金supported by the National Key Research and Development Program of China(2018YFC1004900 and 2018YFC1003100)Natural Science Foundation of Shandong Province(ZR2018PH006 and ZR2018MC014)Key Research and Development Program of Shandong Province(2017G006035)
文摘Balanced reciprocal translocation is one of the most common chromosome abnormalities,with an incidence of approximately 1in every 500 newborns(Mackie Ogilvie and Scriven,2002).Most balanced reciprocal translocation carriers have no observable phenotype because there is no loss or gain of genetic material(Ogilvie et al.,2001).However,the carriers have a risk of infertility.
基金This project was in part supported by the National Natural Science Foundation of China (No.30973196).
文摘The polycystic ovary syndrome (PCOS) model was established in fats and correlation between the expression of macrophage migration inhibitory factor (MIF) and cytokinesis with the MAPK signalling pathway in the rat ovary was measured. The PCOS model in rats was established by dehydroepiandrosterone (DHEA).Thirty sexually immature female Sprague-Dawley rats were randomly and equally assigned to three groups:control group,PCOS group,and PCOS with high-fat diet (HFD) group.Serum hormones were assayed by radioimmunoassay (RIA).The ovaries'were immunohistochemically stained with MIF,and the expression of MIF,p-JNK and p-p38 was detected by Western blotting in ovaries.The serum testosterone level,LH concentration,LH/FSH ratio,fasting insulin level and HOMA IR index in the PCOS group (6.077±0.478,13.809±1.701,1.820±0.404,10.83±1.123 and 1.8692±0.1096)and PCOS with HFD group (6.075±0.439,14.075±1.927,1.779±0.277,10.20±1.377 and 1.7736±0.6851)were significantly higher than those in the control group (4.949±0.337, 2.458±0.509,1.239±0.038,9.53±0.548 and 1.5329±0.7363),but there was no significant difference between the PCOS group and PCOS with HFD group.The expression levels of MIF,p-JNK,and p-p38 in the PCOS group (0.4048±0.013,0.6233±0.093 and 0.7987±0.061)and PCOS withHFD group (0.1929±0.012,0.3346±0.103 and 0.3468±0.031)were obviously higher than those in control group (0.2492±0.013, 0.3271±0.093 and 0.3393±0.061),but no Significant difference was observed between PCOS group and PCOS with HFD group.It was suggested that MIF may participate in the pathogenesis of PCOS through the MAPK signalling pathway in PCOS rats induced by DHEA.
文摘Semen from 5210 sperm bank donors was analyzed and trends in semen quality were evaluated at Shandong Human Sperm Bank between 2008 and 2014. After 2-7 days of abstinence, semen samples were collected. Measurements of semen volume, sperm concentration, sperm forward motility, and total sperm count were performed. There were significant declining trends in semen volume, sperm concentration, sperm forward motility, and total sperm count. Our results indicate that the quality of semen in this cohort of sperm donors had decreased during the study period.
基金This work was supported by the National Natural Science Foundation of China(No.81471498 and 81760272)the Shandong Scientific Research and Technology Development project(No.2014GSF118129)+1 种基金the Guangxi Natural Science Foundation(No.2016GXNSFDA380010)the Guangxi Scientific Research and Technology Development project(No.Guikegong 1355005-5-7).
文摘Antisperm antibodies(ASAs)are assumed to be a possible causative factor for male infertility,with ASAs detected in 5%-15%of infertile men but in only l%-2%of fertile ones.It remains unclear whether ASAs have an adverse effect on the outcome of in v/tro fertilization(IVF)or intracytoplasmic sperm injection(ICSI).This study investigated differences in the rates of fertilization,pregnancy,and live births associated with serum ASA-positive and ASA-negative men following IVF or ICSI.Five hundred and fifty-four consecutive infertile couples undergoing IVF(n=399)or ICSI(n=155)were included.The two-sample two-sided t-test and Chi-square or Fisher's exact test was used for statistical analysis.Lower rates of fertilization(41.7%vs 54.8%,P=0.03),good embryos(18.9%vs 35.2%,P=0.00),pregnancy(38.5%vs 59.4%,P=0.00),and live births(25.8%vs 42.5%,P=0.00)were observed in men of the IVF group with a positive serum ASA than in those with a negative ASA.ASA positivity/negativity correlated with pregnancy rates(P=0.021,odds ratio[OR]:0.630,95%confidence interval[Cl]:0.425-0.932)and live birth rates(P=0.010,OR:1.409,95%Cl:1.084-1.831)after controlling for the female serum follicle-stimulating hormone level and the couple's ages at IVF.Women coupled with ASA-positive men had lower live birth rates with IVF than with ICSI(25.8%and 47.4%,respectively;P=0.07).Women coupled with ASA-positive men had lower rates of pregnancy and live births following IVF than those coupled with ASA-negative men but had a similar outcome with ICSI.
基金This work was supported by the National Natural Science Foundation of China （No.1471456）, and Guidance Foundation of Renmin Hospital of Wuhan University （No. RMYD2018Z13）.
文摘This study aimed to explore the outcomes of progestin-primed ovarian stimulation protocol （PPOS） in aged infertile women who failed to get pregnant in the first IVF/ICSI-ET cycles with GnRH-a long protocol. A self-controlled study was conducted to retrospectively investigate the clinical outcomes of 104 aged infertile patients who didn＇t get pregnant in the first IVF/ICSI-ET treatment by stimulating with GnRH-a long protocol （non-PPOS group）, and underwent PPOS protocol （PPOS group） in the second cycle between January 2016 and December 2016 in the Center for Reproductive Medicine, Renmin Hospital of Wuhan University. The primary outcomes included clinical pregnancy rate of frozen-thawed embryos transfer （FET） in PPOS group, and good-quality embryo rate in both groups. The secondary outcomes were fertilization rate, egg utilization rate and cycle cancellation rate. The results showed that there were no significant differences in basal follicle stimulating hormone （bFSH）, antral follicle count （AFC）, duration and total dosage of gonadotropin （Gn）, number of oocytes retrieved, intracytoplasmic sperm injection （ICSI） rate, fertilization rate, and cycle cancellation rate between the two groups （P〉0.05）. However, the oocyte utilization rate and good-quality embryo rate in PPOS group were significantly higher than those in non-PPOS group （P〈0.05）. By the end of April 2017, 62 FET cycles were conducted in PPOS group. The clinical pregnancy rate and embryo implantation rate were 22.58% and 12.70%, respectively. In conclusion, PPOS protocol may provide better clinical outcomes by improving the oocyte utilization rate and good-quality embryo rate for aged infertile patients who failed to get pregnant in the first IVF/ ICSI-ET cycles.
基金the Key Research and Development Program of Shandong Province(2019GSF108237)the Young Scholars Program of Shandong University(2016WLJH50)the Natural Science Foundation of Shandong Province(ZR2017MH049).
文摘There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men.Here,we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del(p.D51fs)frame-shift mutation in exon 3 of the testis expressed 11(TEX11)gene in one patient.Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation.Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes.In contrast,testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression.Western blotting of human embryonic kidney(HEK293)cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression.In conclusion,we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient,emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.
文摘The purpose of this study was to determine the diagnostic accuracy of serum inhibin B(INHB)as a predictor of the retrieval outcome of testicular haploid gametes(spermatids and testicular spermatozoa)in nonobstructive azoospermic men.Serum hormone levels,testicular volume,and histological evaluation were performed in 403 Chin ese non obstructive azoospermic men.Testicular haploid gamete was successfully retrieved in 213 of 403 patients(52.85%).The haploid gamete group always had higher INHB levels than the non-haploid gamete group.According to the receiver operating characteristic(ROC)curve analysis,INHB was a good predictor of testicular haploid gamete retrieval outcome in all patients(sensitivity:77.93%and specificity:91.58%)and patients with normal follicle-stimulating hormone(FSH;sensitivity:88.52%and specificity:70.83%).The area under the ROC curve(AUC)of INHB was similar to that of FSH in all patients or patients with normal FSH.In patients with elevated FSH,INHB was superior to FSH in predicting the presence of haploid gamete(AUC:0.73 vs 0.55,P<0.05),with a sensitivity of 60.00%and a specificity of 80.28%.It con eluded that serum INHB as an effective marker for spermatoge nesis was a sign ificant predictor of testicular haploid gamete retrieval outcomes in nonobstructive azoospermic men.Especially,INHB is superior to FSH in predicting the presenee of haploid gamete in the patients with elevated FSH.
基金ACKNOWLEDGMENTS This work was partly supported by： projects of Technology Development Program of Shandong Province （No. 2014GSF 118033） Youth Funds of National Natural Science Foundation of China （No. 30901488）+2 种基金 Doctor Start Fund of Natural Science Foundation of Guangdong Province （No. 9451008901003001）Medical Science and Technology Research Foundation of Guangdong Province （No. A2008189） Foundation for Outstanding Young Scientist in Shandong Province （No. 2004BS02019） and Independent Innovation Funds of Center for Reproductive Medicine of Shandong University. These organizations aided in the design and conduct of the study as well as in the collection, management, and analysis of the data.
文摘We aim to investigate the correlations between hemodynamic parameters, penile rigidity grading, and the therapeutic effects of phosphodiesterase type 5 inhibitors using color Doppler flow imaging after intracavernosal injection in patients with erectile dysfunction. This study involved 164 patients. After intracavernosal injection with a mixture of papaverine （60 mg）, prostaglandin E1 （10 μg）, and lidocaine （2%, 0.5-1 ml）, the penile vessels were assessed using color Doppler flow imaging. Penile rigidity was classified based on the Erection Hardness Score system as Grades 4, 3, 2 or 1 （corresponding to Schramek Grades Ⅴ to Ⅱ）. Then, the patients were given oral sildenafil （50-100 mg） and scored according to the International Index of Erectile Function （IIEF-5） questionnaire. The number of patients with penile rigidities of Schramek Grades Ⅱ to Ⅴ was 14, 18, 21, and 111, respectively. The IIEF-5 score was positively correlated with the refilling index of the penile cavernosal artery （r = 0.79, P 〈 0.05）, the peak systolic velocity （r= 0.45, P〈 0.05）, and penile rigidity （r= 0.75, P〈 0.05）, and was negatively correlated with the end diastolic velocity （r = -0.74, P 〈 0.05）. For patients with erectile dysfunction, both the IIEF-5 score after sildenafil administration, which is correlated with penile rigidity, and the hemodynamic parameters detected using color Doppler flow imaging may predict the effects of phosphodiesterase type 5 inhibitor treatment and could provide a reasonable model for the targeted-treatment of erectile dysfunction.
基金This work is supported by grants from the National Key R&D Program of China(2018YFC1003700,2018YFC1003400)National Natural Science Foundation of China(31671293,31801203,and 31890782).
文摘Repairing DNA double-strand breaks(DSBs)with homologous chromosomes as templates is the hallmark of meiosis.The critical outcome of meiotic homologous recombination is crossovers,which ensure faithful chromosome segregation and promote genetic diversity of progenies.Crossover patterns are tightly controlled and exhibit three characteristics:obligatory crossover,crossover interference,and crossover homeostasis.Aberrant crossover patterns are the leading cause of infertility,miscarriage,and congenital disease.Crossover recombination occurs in the context of meiotic chromosomes,and it is tightly integrated with and regulated by meiotic chromosome structure both locally and globally.Meiotic chromosomes are organized in a loop-axis architecture.Diverse evidence shows that chromosome axis length determines crossover frequency.Interestingly,short chromosomes show different crossover patterns compared to long chromosomes.A high frequency of human embryos are aneuploid,primarily derived from female meiosis errors.Dramatically increased aneuploidy in older women is the well-known“maternal age effect.”However,a high frequency of aneuploidy also occurs in young women,derived from crossover maturation inefficiency in human females.In addition,frequency of human aneuploidy also shows other age-dependent alterations.Here,current advances in the understanding of these issues are reviewed,regulation of crossover patterns by meiotic chromosomes are discussed,and issues that remain to be investigated are suggested.
文摘The impact of prior cesarean section（CS） on the pregnancy and neonatal outcomes of in vitro fertilization and embryo transfer（IVF-ET） was investigated. A retrospective analysis was performed on 144 patients with prior CS between January 2013 and December 2015. The pregnancy, delivery, and neonatal outcomes of patients who had previous CS delivery and received IVF-ET were analyzed. The control group comprised 166 patients who had only previous vaginal delivery（VD） and received IVF-ET during the same period. The results showed that the basal follicle stimulating hormone level, estradiol level on human chorionic gonadotropin（h CG） day, gonadotrophin dosage, duration of stimulation, retrieved oocytes, fertilization rate, high-quality embryo rate, multiple birth rate, abortion rate and ectopic pregnancy rate had no significant difference between the two groups（P〉0.05）. The pregnancy rate（40.28% vs. 54.22%） and implantation rate（24.01% vs. 34.67%） were significantly lower（P〈0.05）, and the ratio of embryo difficulty transfer（9/144 vs. 0/166） was significantly higher in CS group than in VD group. The risk of pernicious placenta previa and postpartum hemorrhage in twin deliveries was significantly increased in CS group as compared with that in VD group（P〈0.05）, and gestational age and neonatal birth weight were significantly reduced in twin deliveries as compared with singleton deliveries in both groups（P〈0.05）. It was suggested that the existence of CS scar may impact embryo implantation and clinical pregnancy outcome, and increase the difficulty of ET. We should limit the number of transfer embryos to avoid multiple pregnancies and strengthen gestational supervision in patients with cesarean scar.
文摘Testicular sperm extraction is a common procedure used to find spermatogenic cells in men with nonobstructive azoospermia. The laboratory processing of biopsied testicular tissues needs to be performed meticulously to acquire a high yield of cells. In this study, the effectiveness of mincing the tissues after testicular biopsy was assessed using histological evaluation, as was the possible adverse effect of residual tissue on the migration of spermatogenic cells during density gradient centrifugation. Our results indicate that testicular residual tissue, when laid on the density gradient medium along with the sperm wash, hinders the spermatogenic cells＇ forming a pellet during centrifugation, and therefore impairs the intracytoplasmic sperm injection procedure. Whereas the mean number of recovered cells from the sperm wash medium （SWM） with residual tissue is 39.435 ~ 24.849, it was notably higher （60.189 ~ 28.214 cells） in the SWM without minced tissues. The remaining tissue contained no functional seminiferous tubules or spermatogenic cells in histological sections. In conclusion, the remaining residual tissue after mincing biopsied testicular tissue does not add any functional or cellular contribution to spermatogenic cell retrieval; in fact, it may block the cellular elements in the accompanying cell suspension from migrating through the gradient layers to form a pellet during centrifugation and cause loss of spermatogenic cells.
基金supported by the National Key Research and Development Program of China(Nos.2018YFC1002804 and 2016YFC1000600)the National Natural Science Foundation of China(Nos.81771618 and 81971356)the Fundamental Research Funds for the Central Universities(No.2042023kf0028).
文摘Objective Innate lymphoid cells(ILCs)are a class of newly discovered immunocytes.Group 1 ILCs(ILC1s)are identified in the decidua of humans and mice.High mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related diseases.Furthermore,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway.This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway.Methods Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different groups.The targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated.In addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,respectively.Furthermore,changes of the NF-κB signaling pathway in ILC1s were examined in the different groups.For the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling pathway.Results The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway,and attenuate the inflammation at the maternal-fetal interface in abortive mice.
基金Project supported by the National Natural Science Foundation of China(No.81571414)the key Research and Development Program of Shandong Province(No.2015gsf118124)the Chinese Medical Association of Clinical Medicine Research Special Funds(No.16020290645),China
文摘This study aimed to evaluate fertility and onco-logic outcomes in women with complex hyperplasia(CH)or complex atypical hyperplasia(CAH)who received fertility-sparing therapy and in vitro fertili-zation(IVF).Endometrial carcinoma is the most common carcinoma of the female genital tract(Stu-bert and Gerber,2016),and is associated with endo-metrial hyperplasia(EH)resulting from long-term unopposed estrogenic stimulation of the endometrium.EH is characterized by non-physiological prolifera-tion of endometrium that results in glands with ir-regular shapes and varying sizes(Horn et al.,2007).The World Health Organization(WHO)classified it into four types:simple or complex hyperplasia with or without atypia.CH is characterized by glands with irregular outlines that demonstrate marked structural complexity and back-to-back crowding.Atypical hyperplasia designates a proliferation of glands ex-hibiting cytologic atypia,in which varying degrees of nuclear atypia and loss of polarity are present(Kur-man et al.,1985).It has been reported that high-dose progestin is safe and efficient for CAH or early-stage low-grade carcinoma for young women who desire fertility-preserving treatment(Randall and Kurman,1997).However,few studies have reported the dif-ferences of pregnancy outcomes between patients with CAH and CH,while those patients take a great proportion in people suffered from infertility.More studies about the outcome of IVF are needed.Our aim is to evaluate fertility and oncological outcomes in women with CH or CAH who received fertility-sparing therapy.
文摘Dear Editor, Klinefelter syndrome （KS） is the most frequent genetic cause of infertility in men. Paternity can be achieved through intracytoplasmic sperm injection （ICSI） with spermatozoa recovered from ejaculated semen if exist, or testes with testicular sperm extraction （TESE）.
基金supported by the National Key Research and Development Program of China(No.2022YFC2703200 and No.2021YFC2700600).
文摘In this study,we aimed to assess the effect of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection on semenparameters.The study comprised 110 sperm volunteers who self-reported SARS-CoV-2 infection from the Human Sperm Bank ofthe Center for Reproductive Medicine,Shandong University(Jinan,China).The volunteers had normal sperm concentration beforeinfection.Each volunteer provided semen samples before and after infection.We selected 90 days after infection as the cutoff point.Semen parameters within 90 days after infection of 109 volunteers(group A)were compared with semen parameters before infection.Moreover,semen parameters on or after 90 days after infection of 36 volunteers(group B)were compared with semen parameters beforeinfection.Furthermore,based on whether the volunteers had completed the three-dose SARS-CoV-2 vaccination booster,volunteersin group A and B were further divided into two subgroups separately.Semen parameters were compared before and after infection ineach subgroup.Our results showed that in this cohort population,the semen quality in volunteers with normal sperm concentrationsbefore infection decreased after SARS-CoV-2 infection within 90 days,while the semen quality returned to preinfection levels after 90days.The completion of a three-dose SARS-CoV-2 vaccination booster may exert a protective effect on semen quality after infection.
基金supported by the National Key R&D Program of China(2023YFC2705503)Major Innovation Projects in Shandong Province(2021ZDSYS16)+4 种基金the National Natural Science Foundation of China(82071699 and 82371619)CAMS Innovation Fund for Medical Sciences(2021-I2M-5-001)the Basic Science Center Program of NSFC(31988101)Science Foundation for Distinguished Young Scholars of Shandong(ZR2021JQ27)Taishan Scholars Program for Young Experts of Shandong Province(tsqn202103192)。
文摘Non-obstructive azoospermia(NOA),the lack of sperm in the ejaculate due to failure of spermatogenesis,can result from a variety of diverse factors,with genetic factors accounting for~30%of NOA cases,including chromosomal aberrations,Y-chromosome microdeletions,and monogenic variants(Tang et al.,2022).More than 2000genes are known to participate in spermatogenesis,and>400 genes specifically linked to azoospermia have been identified through studies in mouse models(Krausz and Riera-Escamilla,2018).However,relatively few genes associated with azoospermia in mice have been verified in humans.
基金supported by the grants from National Natural Science Foundation of China(No.81401276,No.81771618 and No.81771662)the Fund Project of Health and Family Planning Commission of Hubei Province(No.WJ2015MA006 and No.WJ2015Q017)
文摘E2A is involved in promoting forkhead box P3（FOXP3） and retinoid-related orphan receptor gamma t（RORγt） gene transcription, which are pivotal transcription factors of T regulatory cells and Th17 cells, respectively. Little is known about the involvement of E2 A in pregnancy process. This study aimed to investigate the expression of E2 A, cytotoxic T-lymphocyte-associated protein 4（CTLA-4）, and Foxp3 in luteal phase endometrium of women suffering recurrent miscarriage（RM）（n=21） and control group（n=11） by immunohistochemistry, with the Vectra？ automated quantitative pathology imaging system for analysis. The percentage of E2 A＋ cells and CTLA-4＋ cells was significantly higher in the endometrium of women with RM than in the controls. There was positive correlation between E2 A and CTLA-4（r=0.523, P=0.002）, E2 A and FOXP3（r=0.380, P=0.032）, and FOXP3 and CTLA-4（r=0.625, P=0.000） in the mid-secretory phase of endometrium for all subjects. It was concluded that the abnormal expression of endometrial E2 A existed in mid-secretory endometrium of women with RM, and there was a positive correlation between E2 A and FOXP3, and E2 A and CTLA-4, suggesting the possible regulation role of E2 A involved in regulating endometrium receptivity.
基金supported by grants from the National Basic Research Program of China(973 program)(Nos.2012CB944700 and 2011CB944502)the National Natural Science Foundation of China(No.31371453)+1 种基金the Scientific Research Foundation of Shandong Province of Outstanding Young Scientist(No.2012BSE27089)2012 Shandong Province Post-Doctoral Innovation Foundation(Nos.201102017 and 201203052)
文摘The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone（FSH） on follicular growth and granulosa cell gonadotropin receptor m RNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages（days 1–7）,but inhibited at later stage（days 7–14） of in vitro culture. Interestingly,testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH（400 m IU/m L）. In addition,in cultured granulosa cells,high testosterone concentrations induced cell proliferation,and increased the m RNA expression level of FSH receptor（FSHR）,and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development,most likely through regulation of the FSH signaling pathway,although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.
基金supported by grants from the National Key Research and Development Program of China(No.2021YFC2701405)the National Natural Science Foundation of China(Nos.82171614 and 82271656),Beijing Natural Science Foundation(No.7232125).
文摘To the Editor:Septate uterus is the most common congenital uterine malformation associated with an increased risk of miscarriage,preterm birth,and fetal malpresentation and reduced clinical pregnancy rates.The European classification defines septate uterus as having an internal fundal indentation exceeding 50%of the uterine wall thickness and an external indentation less than 50%of the uterine wall thickness.
