The genome tagging project(GTP)plays a pivotal role in addressing a critical gap in the understanding of protein functions.Within this framework,we successfully generated a human influenza hemagglutinin-tagged sperm-s...The genome tagging project(GTP)plays a pivotal role in addressing a critical gap in the understanding of protein functions.Within this framework,we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411(HA-tagged Ssp411)mouse model.This model is instrumental in probing the expression and function of Ssp411.Our research revealed that Ssp411 is expressed in the round spermatids,elongating spermatids,elongated spermatids,and epididymal spermatozoa.The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis.Nevertheless,rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions.Ssp411 is not detectable in metaphase Ⅱ(MⅡ)oocytes,zygotes,or 2-cell stage embryos,highlighting its intricate role in early embryonic development.These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP,fostering groundbreaking advancements in the f ields of spermiogenesis and reproductive biology.展开更多
Natural products play a crucial role in new drug development,but their druggability is often limited by uncertain molecular targets and insufficient research on mechanisms of action.In this study,we developed a new RP...Natural products play a crucial role in new drug development,but their druggability is often limited by uncertain molecular targets and insufficient research on mechanisms of action.In this study,we developed a new RPL19-TRAP^(KI)-seq method,combining CRISPR/Cas9 and TRAP technologies,to investigate these mechanisms.We identified and validated seven ribosomal large subunit surface proteins suitable for TRAP,selecting RPL19 for its high enrichment.We successfully established a stable cell line expressing EGFP-RPL19 using CRISPR knock-in and verified its efficiency and specificity in enriching ribosomes and translating mRNA.Integrated with next-generation sequencing,this method allows precise detection of translating mRNA.We validated RPL19-TRAP^(KI)-seq by investigating rapamycin,an mTOR inhibitor,yielding results consistent with previous reports.This optimized TRAP technology provides an accurate representation of translating mRNA,closely reflecting protein expression levels.Furthermore,we investigated SBF-1,a 23-oxa-analog of natural saponin OSW-1 with significant anti-tumor activity but an unclear mechanism.Using RPL19-TRAP^(KI)-seq,we found that SBF-1 exerts its cytotoxic effects on tumor cells by disturbing cellular oxidative phosphorylation.In conclusion,our method has been proven to be a promising tool that can reveal the mechanisms of small molecules with greater accuracy,setting the stage for future exploration of small molecules and advancing the fields of pharmacology and therapeutic development.展开更多
Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies(ART).So far,the clinical evaluation of embryo quality depends on embryo morphology....Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies(ART).So far,the clinical evaluation of embryo quality depends on embryo morphology.However,the clinical pregnancy rate is still low.Therefore,new indicators are needed to further improve the evaluation of embryo quality.Several studies have shown that the decrease of sperm-specific protein actin-like 7A(ACTL7A)leaded to low fertilization rate,poor embryo development,and even infertility.The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality.In this study,excluding the factors of severe female infertility,a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization(IVF)laboratory outcomes.Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality.Furthermore,the protein levels showed a significant correlation with fertilization outcomes of ART.ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest.In conclusion,sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.展开更多
Dear Editor,Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) induced human disease, the coronavirus disease 2019(COVID-19),has been reported in more than 200 countries a...Dear Editor,Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) induced human disease, the coronavirus disease 2019(COVID-19),has been reported in more than 200 countries and areas around the world(Wu et al. 2020).展开更多
Advanced paternal age has been overlooked,and its effect on fertility remains controversial.Previous studies have focused mainly on intracytoplasmic sperm injection(ICSI)cycles in men with oligozoospermia.However,few ...Advanced paternal age has been overlooked,and its effect on fertility remains controversial.Previous studies have focused mainly on intracytoplasmic sperm injection(ICSI)cycles in men with oligozoospermia.However,few studies have reported on men with semen parameters within reference ranges.Therefore,we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization(IVF)cycles.In total,381 cycles included were subgrouped according to paternal age(<35-year-old,35–39-year-old,or≥40-year-old),and maternal age was limited to under 35 years.Data on embryo quality and clinical outcomes were analyzed.The results showed that fertilization and high-quality embryo rates were not significantly different(all P>0.05).The pregnancy rate was not significantly different in the 35–39-year-old group(42.0%;P>0.05),but was significantly lower in the≥40-year-old group(26.1%;P<0.05)than that in the<35-year-old group(40.3%).Similarly,the implantation rate significantly decreased in the≥40-year-old group(18.8%)compared with that in the<35-year-old group(31.1%)and 35–39-year-old group(30.0%)(both P<0.05).The live birth rate(30.6%,21.7%,and 19.6%)was not significantly different across the paternal age subgroups(<35-year-old,35–39-year-old,and≥40-year-old,respectively;all P>0.05),but showed a declining trend.The miscarriage rate significantly increased in the 35–39-year-old group(44.8%)compared with that in the<35-year-old group(21.0%;P<0.05).No abnormality in newborn birth weight was found.The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters,although it has no impact on embryo development.展开更多
Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian c...Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese women.Methods Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian cysts.Results The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)quartiles.As compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/L.Conclusion:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.展开更多
Male infertility is a global issue caused by poor sperm quality,particularly motility.Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology(ART)treatment.Scriptaid,wit...Male infertility is a global issue caused by poor sperm quality,particularly motility.Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology(ART)treatment.Scriptaid,with a novel human sperm motility-stimulating activity,has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART.We evaluated the effects of Scriptaid on asthenozoospermic(AZS)semen,including its impact on motility stimulation and protective effects on cryopreservation and duration of motility,by computer-aided sperm analysis(CASA).Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity,tyrosine phosphorylation,adenosine triphosphate(ATP)concentration,mitochondrial membrane potential,and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection(ICSI)experiments.Furthermore,our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function.In summary,Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality,prolongs sperm viability,and increases the fertilization rate.展开更多
Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression le...Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression levels of CD8^(+)T cells in the decidua,peripheral blood,and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry.Decidual CD8^(+)T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression.The placental CEACAM1 protein expression was analyzed using immunohistochemistry.Results:Tim-3^(+)CD8^(+)T cells were more abundant in the decidua than in the peripheral blood.Tim-3 expression in the decidual CD8^(+)T cells was significantly lower in PE patients.Decidual Tim-3^(+)CD8^(+)T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ,but lower levels of the Th2-type cytokine IL-4.CEACAM1 altered the CD107a,IFN-γ,and IL-4 levels;this was reversed by anti-Tim-3 antibodies.The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs.Conclusions:Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE,accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8^(+)T cells.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: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
Mesenchymal stem cells(MSCs),which are pluripotent cells with immunomodulatory properties,have been considered good candidates for the therapy of several immune disorders,such as inflammatory bowel diseases,concanaval...Mesenchymal stem cells(MSCs),which are pluripotent cells with immunomodulatory properties,have been considered good candidates for the therapy of several immune disorders,such as inflammatory bowel diseases,concanavalin A-induced liver injury,and graft-versus-host disease.The embryo is a natural allograft to the maternal immune system.A successful pregnancy depends on the timely extinction of the inflammatory response induced by embryo implantation,followed by the switch to a tolerant immune microenvironment in both the uterus and the system.Excessive infiltration of immune cells and serious inflammatory responses are triggers for embryo rejection,which results in miscarriage.Here,we demonstrated that adoptive transfer of MSCs could prevent fetal loss in a lipopolysaccharide(LPS)-induced abortion model and immune response-mediated spontaneous abortion model.The immunosuppressive MSCs alleviated excessive inflammation by inhibiting CD4+T cell proliferation and promoting the decidual macrophage switch to M2 in a tumor necrosis factor-stimulated gene-6(TSG-6)-dependent manner.Cell-tocell contact with proinflammatory macrophages increased the TSG-6 production by the MSCs,thereby enhancing the suppressive regulation of T cells and macrophages.Moreover,proinflammatory macrophages in contact with the MSCs upregulated the expression of CD200 on the stem cells and facilitated the reprogramming of macrophages towards an anti-inflammatory skew through the interaction of CD200 with CD200R on proinflammatory macrophages.Therefore,the results demonstrate that a TSG-6-mediated paracrine effect,reinforced by cell-to-cell contact between MSCs and proinflammatory macrophages,is involved in the mechanism of MSC-mediated abortion relief through the induction of immune tolerance.Our study also indicates the potential application of MSCs in clinical recurrent miscarriages.展开更多
Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced mosaicism.iSTOP enables dir...Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced mosaicism.iSTOP enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for fertility.Here,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona pellucida.We further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO offspring.We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport.Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.展开更多
Early embryonic development is a complex process.The zygote undergoes several rounds of division to form a blastocyst,and during this process,the zygote undergoes the maternal-to-zygotic transition to gain control of ...Early embryonic development is a complex process.The zygote undergoes several rounds of division to form a blastocyst,and during this process,the zygote undergoes the maternal-to-zygotic transition to gain control of embryonic development and makes two cell fate decisions to differentiate into an embryonic and two extra-embryonic lineages.With the use of new molecular biotechnologies and animal models,we can now further study the molecular mechanisms of early embryonic development and the pathological causes of early embryonic arrest.Here,we first summarize the known molecular regulatory mechanisms of early embryonic development in mice.Then we discuss the pathological factors leading to the early embryonic arrest.We hope that this review will give researchers a relatively complete view of the physiology and pathology of early embryonic development.展开更多
Aspirin,one of the most widely applied medicines,not only possesses the effects on reducing fever,anti-vascular hyperplasia,and anti-inflammation,but also has the capacity of preventing platelet aggregation.So far,it ...Aspirin,one of the most widely applied medicines,not only possesses the effects on reducing fever,anti-vascular hyperplasia,and anti-inflammation,but also has the capacity of preventing platelet aggregation.So far,it is acceptable to adopt aspirin,especially low-dose aspirin(LDA),to prevent pregnancy-related complications,such as pregnancy complicated by antiphospholipid syndrome,systemic lupus erythematosus,or preeclampsia;unexplained recurrent spontaneous abortion;fetal growth restriction;and preterm birth.In this article,we reviewed the possible mechanism of action and applications of aspirin in these pregnancy-related complications.展开更多
Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cell...Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cells(PSCs),known as mural cells covering the vasculature,are essential for blood vessel formation and postulated as progenitors of mesenchymal stem cells(MSCs).2,3 We previously established umbilical cord artery-derived PSCs(UCA-PSCs)and Wharton’s jelly-derived MSCs(WJ-MSCs)and UCAPSCs display optimal angiogenic capacity in vitro.4 Therefore,we explored the angiogenesis and pro-angiogenesis mechanisms of UCA-PSCs and provided them as an efficient treatment strategy for ovarian failure.展开更多
Objective:Testosterone deficiency may be a risk factor for lower urinary tract symptoms(LUTS),and there may be a causal ink between the emergence of LUTS and the incidence of late-onset hypogonadism(LOH).We perfomed a...Objective:Testosterone deficiency may be a risk factor for lower urinary tract symptoms(LUTS),and there may be a causal ink between the emergence of LUTS and the incidence of late-onset hypogonadism(LOH).We perfomed an epidemiologic study to investigate the association between symptomatic late-onset hypogonadism(SLOH)and LUTS in middle-aged and elderly rural Chinese males.Methods:A total of 965 men completed a questionnaire and underwent a detailed physical examination.The Aging Males'Symptoms(AMS)scale was used to assess SLOH,and the International Prostate Symptom Score(IPSS)questionnaire was used to assess LUTS.Serum reproductive hormone levels of testosterone,sex hormone-binding globulin(SHBG)and luteinizing hormone(LH)were measured.Results:A total of 965 males(mean age:56.34±8.85,range:40-80 years)were recruited for the present study.A total of 20.93%(202/965)were diagnosed with SLOH.A total of 93.16%(899/965)had mild LUTS,5.18%(50/965)had moderate LUTS,and 1.66%(16/965)had severe LUTS.Among SLOH patients,13.40%(27/202)and 3.90%(8/202)had moderate and severe LUTS,respectively.Patients with severe LUTS had increased SHBG and LH compared with those with mild and moderate LUTS(P<0.01).Correlation analysis revealed that the AMS total score was positively correlated with the IPSS score(P<0.05).The prevalence of SLOH was significantly increased with LUTS severity In addition to the known effect of age,the results of mutiple regression analysis also showed that serum LH or SHBG appeared to have a weak link with SLOH and LUTS that requires etiological and biological clarification in our future study.Conclusion:In this cross-sectional analysis of SLOH and LUTS,LUTS severity was significantly associated with hypogonadism symptoms.Additionally,the prevalence of SLOH advanced with increasing LUTS severity.Serum SHBG or LH showed a positive correlation with SLOH and LUTS.展开更多
Objective:This large-scale cross-sectional study aims to identify the characteristics of and risk factors associated with sexual repression among internal migrants in China.Methods:Between August 2013 and August 2015,...Objective:This large-scale cross-sectional study aims to identify the characteristics of and risk factors associated with sexual repression among internal migrants in China.Methods:Between August 2013 and August 2015,a total of 8,669 internal migrants from four major cities in China(Beijing,Shanghai,Chengdu,and Chongqing)voluntarily participated in our study.They were interviewed,and the data on their demographic information,occupation,and sexual activities were collected.The Chi-square test and multiple logistic regressions were conducted to identify significant associations.A stepwise method was adopted for the selection of variables.Results:There were 3,597(41.49%)males and 5,072(58.51%)females in total.A higher percentage of males reported that they felt sexual repression compared to females(14.43%vs.9.21%).After adjusting for other covariates,the consequence was showed that male migrants working for more than 5 days were more likely to report sexual repression(odds ratio[OR]=1.40,P<0.05).Living in a collective dormitory with others was also a risk factor for male migrants.The longer males spent with their partners,the less sexual repression occurred(OR=0.94,P<0.05).Similarly,agricultural household registration status and working for more than 5 days increased the risk for sexual repression among female migrants(OR=1.41 and OR=1.46,respectively,P<0.05).Frequent and constructive communication also protected females against sexual repression(P<0.05).Well-educated females experienced relatively less sexual repression when compared to their counterparts with less education(P<0.05).Conclusions:Sexual repression was significantly associated with a few demographic,occupational,and sexual risk factors.Meaningful differences have been identified between male and female migrants.More effective intervention programs such as safeguard measures and welfare policies should be designed and implemented for a majority of female migrants and for those with agricultural household registration status.展开更多
Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus.The interaction between decidualγδT cells and trophoblasts plays a pivotal role during successfu...Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus.The interaction between decidualγδT cells and trophoblasts plays a pivotal role during successful pregnancy;however,their physiological functions in early-term human pregnancy are still not completely illustrated.This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidualγδT cells and HTR8/SVneo trophoblast cells.Methods::The percentile of CXCR6+γδT cells in the peripheral blood from normal female and recurrent spontaneous abortion(RSA)patients was analyzed by flow cytometry.The expression of CXCR6 was detected in decidual immune cells via flow cytometry,and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus(LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay.Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells.Expression of granzyme B and cytokines and proliferation of decidualγδT cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry.Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay.Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss.Results::The percentile of CXCR6+γδT cells in the peripheral blood from RSA patients was lower than normal pregnancies.The expression of CXCR6 was highest in the decidualγδT cells among decidual immune cells,and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased.Expression of granzyme B in the decidualγδT cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16,and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidualγδT cells.Both the expression of CXCR6 in the decidualγδT cells and proliferation of the decidualγδT cells were promoted by HTR8/SVneo trophoblast cells.On the other hand,decidualγδT cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation.In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidualγδT cells and trophoblasts.Conclusions::Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidualγδT cells and trophoblasts,and it showed a light on the effective strategy of adoptive transfer of CXCR6+γδT cells on the treatment of RSA.This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.展开更多
Pregnancy is a complicated process with intricate cell-to-cell crosstalk and immune regulation.Decidual natural killer(NK)cells account for 50%-70% of decidual immune cells in early pregnancy,suggesting that they play...Pregnancy is a complicated process with intricate cell-to-cell crosstalk and immune regulation.Decidual natural killer(NK)cells account for 50%-70% of decidual immune cells in early pregnancy,suggesting that they play important roles in various events,such as embryo implantation and vascular remodeling.Many studies have shown that decidual NK cells interact with other cells either through direct contact or the secretion factors such as cytokines and chemokines.Hence,this review aimed to present the phenotypic characteristics,classification,and functions of decidual NK cells at the maternal-fetal interface during pregnancy.展开更多
In early pregnancy,the decidua is populated by a large number of natural killer cells(NKs),most of which are CD56bright with a strong capacity to secrete cytokines,differing from peripheral and cord blood NK cells(pNK...In early pregnancy,the decidua is populated by a large number of natural killer cells(NKs),most of which are CD56bright with a strong capacity to secrete cytokines,differing from peripheral and cord blood NK cells(pNKs and cNKs).1,2,3 It is generally believed that uterine NKs are recruited from the peripheral blood and are further educated to develop a decidual NK cell(dNK)-like phenotype in the microenvironment at the maternal-fetal interface.4 However,the defined mechanisms involved in this education remain unclear.展开更多
基金the support from the National Natural Science Foundation of China(No.32070849)The Foundation of Science and Technology Commission of Shanghai Municipality(No.22DX1900400)+1 种基金Science and Technology Commission of Shanghai Municipality(No.23JC1403803)Shanghai Municipal Science and Technology Commission Targeted Funding Project(No.22DX1900400).
文摘The genome tagging project(GTP)plays a pivotal role in addressing a critical gap in the understanding of protein functions.Within this framework,we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411(HA-tagged Ssp411)mouse model.This model is instrumental in probing the expression and function of Ssp411.Our research revealed that Ssp411 is expressed in the round spermatids,elongating spermatids,elongated spermatids,and epididymal spermatozoa.The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis.Nevertheless,rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions.Ssp411 is not detectable in metaphase Ⅱ(MⅡ)oocytes,zygotes,or 2-cell stage embryos,highlighting its intricate role in early embryonic development.These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP,fostering groundbreaking advancements in the f ields of spermiogenesis and reproductive biology.
基金supported by the National Key Research and Development Program of China(No.2022YFC2804800 to W.J.)the National Natural Science Foundation of China(No.22494704.,22137002 to Y.D.,92253305 to W.J.and 31971111 to C.L.)+6 种基金the Science and Technology Commission of Shanghai Municipality(Grant 20JC1410900 to Y.D.)the University Innovation Research Group in Chongqing(No.CXQT21016 to Y.D.)the Chongqing Talent Program Project(No.CQYC20200302119 to Y.D.)High-Level Innovation Platform Cultivation Plan of Chongqing(to Y.D.)Joint Fund of the Natural Science Innovation and Development Foundation of Chongqing(to Y.D.)Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(to W.J.)Chongqing Doctoral Express Entry Project(No.CSTB2022BSXM-JCX0044 to J.H.).
文摘Natural products play a crucial role in new drug development,but their druggability is often limited by uncertain molecular targets and insufficient research on mechanisms of action.In this study,we developed a new RPL19-TRAP^(KI)-seq method,combining CRISPR/Cas9 and TRAP technologies,to investigate these mechanisms.We identified and validated seven ribosomal large subunit surface proteins suitable for TRAP,selecting RPL19 for its high enrichment.We successfully established a stable cell line expressing EGFP-RPL19 using CRISPR knock-in and verified its efficiency and specificity in enriching ribosomes and translating mRNA.Integrated with next-generation sequencing,this method allows precise detection of translating mRNA.We validated RPL19-TRAP^(KI)-seq by investigating rapamycin,an mTOR inhibitor,yielding results consistent with previous reports.This optimized TRAP technology provides an accurate representation of translating mRNA,closely reflecting protein expression levels.Furthermore,we investigated SBF-1,a 23-oxa-analog of natural saponin OSW-1 with significant anti-tumor activity but an unclear mechanism.Using RPL19-TRAP^(KI)-seq,we found that SBF-1 exerts its cytotoxic effects on tumor cells by disturbing cellular oxidative phosphorylation.In conclusion,our method has been proven to be a promising tool that can reveal the mechanisms of small molecules with greater accuracy,setting the stage for future exploration of small molecules and advancing the fields of pharmacology and therapeutic development.
基金supported by the Foundation of Shanghai Municipal Health Commission(No.202140340)National Natural Science Foundation of China(No.82171603)Foundation of Science and Technology Commission of Shanghai Municipality(No.17JC1400902,No.20Z21900402).
文摘Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies(ART).So far,the clinical evaluation of embryo quality depends on embryo morphology.However,the clinical pregnancy rate is still low.Therefore,new indicators are needed to further improve the evaluation of embryo quality.Several studies have shown that the decrease of sperm-specific protein actin-like 7A(ACTL7A)leaded to low fertilization rate,poor embryo development,and even infertility.The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality.In this study,excluding the factors of severe female infertility,a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization(IVF)laboratory outcomes.Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality.Furthermore,the protein levels showed a significant correlation with fertilization outcomes of ART.ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest.In conclusion,sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development.
基金supported by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, National Natural Science Foundation of China (31770933, 81971917 and 81872103)Natural Science Foundation of Colleges in Jiangsu Province (17KJA310005)+1 种基金Open Project Fund from State Key Laboratory of Genetic Engineering, Fudan University (No. SKLGE1903)Key Laboratory of Reproduction Regulation of NHC (No. KF2018-01)。
文摘Dear Editor,Since December 2019, the outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) induced human disease, the coronavirus disease 2019(COVID-19),has been reported in more than 200 countries and areas around the world(Wu et al. 2020).
基金This work was supported by the National Key R&D Program of China(No.2018YFC1005001)the Zhongshan Hospital Youth Fund(No.2019ZSQN57)the National Natural Science Foundation of China(No.81971345).
文摘Advanced paternal age has been overlooked,and its effect on fertility remains controversial.Previous studies have focused mainly on intracytoplasmic sperm injection(ICSI)cycles in men with oligozoospermia.However,few studies have reported on men with semen parameters within reference ranges.Therefore,we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization(IVF)cycles.In total,381 cycles included were subgrouped according to paternal age(<35-year-old,35–39-year-old,or≥40-year-old),and maternal age was limited to under 35 years.Data on embryo quality and clinical outcomes were analyzed.The results showed that fertilization and high-quality embryo rates were not significantly different(all P>0.05).The pregnancy rate was not significantly different in the 35–39-year-old group(42.0%;P>0.05),but was significantly lower in the≥40-year-old group(26.1%;P<0.05)than that in the<35-year-old group(40.3%).Similarly,the implantation rate significantly decreased in the≥40-year-old group(18.8%)compared with that in the<35-year-old group(31.1%)and 35–39-year-old group(30.0%)(both P<0.05).The live birth rate(30.6%,21.7%,and 19.6%)was not significantly different across the paternal age subgroups(<35-year-old,35–39-year-old,and≥40-year-old,respectively;all P>0.05),but showed a declining trend.The miscarriage rate significantly increased in the 35–39-year-old group(44.8%)compared with that in the<35-year-old group(21.0%;P<0.05).No abnormality in newborn birth weight was found.The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters,although it has no impact on embryo development.
基金supported by grants from the NSFC-Regional Innovation and Development Joint Fund(No.U22A20364)the National Key R&D Program of China(No.2021YFC2500500)the National Natural Science Foundation of China(No.81973112,No.92049302)。
文摘Objective Little is known about the association between whole-blood nicotinamide adenine dinucleotide(NAD^(+))levels and nabothian cysts.This study aimed to assess the association between NAD^(+)levels and nabothian cysts in healthy Chinese women.Methods Multivariate logistic regression analysis was performed to analyze the association between NAD^(+)levels and nabothian cysts.Results The mean age was 43.0±11.5 years,and the mean level of NAD^(+)was 31.3±5.3μmol/L.Nabothian cysts occurred in 184(27.7%)participants,with single and multiple cysts in 100(15.0%)and84(12.6%)participants,respectively.The total nabothian cyst prevalence gradually decreased from37.4%to 21.6%from Q1 to Q4 of NAD^(+)and the prevalence of single and multiple nabothian cysts also decreased across the NAD^(+)quartiles.As compared with the highest NAD^(+)quartile(≥34.4μmol/L),the adjusted odds ratios with 95%confidence interval of the NAD^(+)Q1 was 1.89(1.14–3.14)for total nabothian cysts.The risk of total and single nabothian cysts linearly decreased with increasing NAD^(+)levels,while the risk of multiple nabothian cysts decreased more rapidly at NAD^(+)levels of 28.0 to35.0μmol/L.Conclusion:Low NAD^(+)levels were associated with an increased risk of total and multiple nabothian cysts.
文摘Male infertility is a global issue caused by poor sperm quality,particularly motility.Enhancement of the sperm quality may improve the fertilization rate in assisted reproductive technology(ART)treatment.Scriptaid,with a novel human sperm motility-stimulating activity,has been investigated as a prospective agent for improving sperm quality and fertilization rate in ART.We evaluated the effects of Scriptaid on asthenozoospermic(AZS)semen,including its impact on motility stimulation and protective effects on cryopreservation and duration of motility,by computer-aided sperm analysis(CASA).Sperm quality improvement by Scriptaid was characterized by increased hyaluronan-binding activity,tyrosine phosphorylation,adenosine triphosphate(ATP)concentration,mitochondrial membrane potential,and an ameliorated AZS fertilization rate in clinical intracytoplasmic sperm injection(ICSI)experiments.Furthermore,our identification of active Scriptaid analogs and different metabolites induced by Scriptaid in spermatozoa lays a solid foundation for the future biomechanical exploration of sperm function.In summary,Scriptaid is a potential candidate for the treatment of male infertility in vitro as it improves sperm quality,prolongs sperm viability,and increases the fertilization rate.
基金National Natural Science Foundation of China(31700799,31970859,81601311,and 81630036)Shanghai Sailing Program(17YF1411600)+2 种基金Training Program for Young Talents of the Shanghai Health System(2018YQ07)Shanghai Chenguang Program(18CG09)Development Fund of Shanghai Talents(2018110)。
文摘Objective:To investigate the frequency and function of Tim-3^(+)CD8^(+)T cells in the third trimester of normal pregnancies(NPs)and preeclamptic(PE)pregnancies.Methods:T-cell immunoglobulin mucin-3(Tim-3)expression levels of CD8^(+)T cells in the decidua,peripheral blood,and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry.Decidual CD8^(+)T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM1)protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression.The placental CEACAM1 protein expression was analyzed using immunohistochemistry.Results:Tim-3^(+)CD8^(+)T cells were more abundant in the decidua than in the peripheral blood.Tim-3 expression in the decidual CD8^(+)T cells was significantly lower in PE patients.Decidual Tim-3^(+)CD8^(+)T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ,but lower levels of the Th2-type cytokine IL-4.CEACAM1 altered the CD107a,IFN-γ,and IL-4 levels;this was reversed by anti-Tim-3 antibodies.The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs.Conclusions:Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE,accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8^(+)T cells.
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.
基金supported by the National Basic Research Program of China(2015CB943300 and 2017YFC1001403)the Nature Science Foundation from the National Nature Science Foundation of China(NSFC)(81630036,91542116,31570920,81490744,31171437,31270969,81571512,and 81501334)+3 种基金the Innovation-oriented Science and Technology Grant from the NHC Key Laboratory of Reproduction Regulation(CX2017-2)the Program of Shanghai Academic/Technology Research Leader(17XD1400900)the Key Project of Shanghai Municipal Education Commission(MECSM)(14ZZ013)the Key Project of Shanghai Basic Research from Shanghai Municipal Science and Technology Commission(STCSM)(12JC1401600).
文摘Mesenchymal stem cells(MSCs),which are pluripotent cells with immunomodulatory properties,have been considered good candidates for the therapy of several immune disorders,such as inflammatory bowel diseases,concanavalin A-induced liver injury,and graft-versus-host disease.The embryo is a natural allograft to the maternal immune system.A successful pregnancy depends on the timely extinction of the inflammatory response induced by embryo implantation,followed by the switch to a tolerant immune microenvironment in both the uterus and the system.Excessive infiltration of immune cells and serious inflammatory responses are triggers for embryo rejection,which results in miscarriage.Here,we demonstrated that adoptive transfer of MSCs could prevent fetal loss in a lipopolysaccharide(LPS)-induced abortion model and immune response-mediated spontaneous abortion model.The immunosuppressive MSCs alleviated excessive inflammation by inhibiting CD4+T cell proliferation and promoting the decidual macrophage switch to M2 in a tumor necrosis factor-stimulated gene-6(TSG-6)-dependent manner.Cell-tocell contact with proinflammatory macrophages increased the TSG-6 production by the MSCs,thereby enhancing the suppressive regulation of T cells and macrophages.Moreover,proinflammatory macrophages in contact with the MSCs upregulated the expression of CD200 on the stem cells and facilitated the reprogramming of macrophages towards an anti-inflammatory skew through the interaction of CD200 with CD200R on proinflammatory macrophages.Therefore,the results demonstrate that a TSG-6-mediated paracrine effect,reinforced by cell-to-cell contact between MSCs and proinflammatory macrophages,is involved in the mechanism of MSC-mediated abortion relief through the induction of immune tolerance.Our study also indicates the potential application of MSCs in clinical recurrent miscarriages.
基金supported by the National Key Research and Development Program of China(2021YFC2701400)the National Natural Science Foundation of China(32000393,32322017,32288101)。
文摘Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced mosaicism.iSTOP enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for fertility.Here,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona pellucida.We further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO offspring.We ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar transport.Our study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.
基金the National Key Research and Development Program of China(2021YFC2700100)the National Natural Science Foundation of China(32130029,81725006,82171643,81971450,and 82101746).
文摘Early embryonic development is a complex process.The zygote undergoes several rounds of division to form a blastocyst,and during this process,the zygote undergoes the maternal-to-zygotic transition to gain control of embryonic development and makes two cell fate decisions to differentiate into an embryonic and two extra-embryonic lineages.With the use of new molecular biotechnologies and animal models,we can now further study the molecular mechanisms of early embryonic development and the pathological causes of early embryonic arrest.Here,we first summarize the known molecular regulatory mechanisms of early embryonic development in mice.Then we discuss the pathological factors leading to the early embryonic arrest.We hope that this review will give researchers a relatively complete view of the physiology and pathology of early embryonic development.
基金supported by the Program of the National Natural Science Foundation of China(No.31970798,31671200)Innovation-oriented Science and Technology Grant from NPFPC Key Laboratory of Reproduction Regulation(CX2017-2)the Program for Zhuoxue of Fudan University,China.
文摘Aspirin,one of the most widely applied medicines,not only possesses the effects on reducing fever,anti-vascular hyperplasia,and anti-inflammation,but also has the capacity of preventing platelet aggregation.So far,it is acceptable to adopt aspirin,especially low-dose aspirin(LDA),to prevent pregnancy-related complications,such as pregnancy complicated by antiphospholipid syndrome,systemic lupus erythematosus,or preeclampsia;unexplained recurrent spontaneous abortion;fetal growth restriction;and preterm birth.In this article,we reviewed the possible mechanism of action and applications of aspirin in these pregnancy-related complications.
基金supported by grants from the National Key Research and Development Program of China(2018YFC1004701)Nature Science Foundation of China(81871128 and 81571391)+4 种基金Nanjing Medical Science Development Project(ZKX16042)L.D.grants from Nature Science Foundation of China(82030040)Jiangsu Province Social Development Project(BE2018602)H.S.For this work,Bruno Péault has been supported by grants from the British Heart Foundation and BIRAX Regenerative Medicine Initiative.
文摘Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular development.Angiogenesis plays a vital role in repairing ovarian damage.1 Perivascular stem cells(PSCs),known as mural cells covering the vasculature,are essential for blood vessel formation and postulated as progenitors of mesenchymal stem cells(MSCs).2,3 We previously established umbilical cord artery-derived PSCs(UCA-PSCs)and Wharton’s jelly-derived MSCs(WJ-MSCs)and UCAPSCs display optimal angiogenic capacity in vitro.4 Therefore,we explored the angiogenesis and pro-angiogenesis mechanisms of UCA-PSCs and provided them as an efficient treatment strategy for ovarian failure.
文摘Objective:Testosterone deficiency may be a risk factor for lower urinary tract symptoms(LUTS),and there may be a causal ink between the emergence of LUTS and the incidence of late-onset hypogonadism(LOH).We perfomed an epidemiologic study to investigate the association between symptomatic late-onset hypogonadism(SLOH)and LUTS in middle-aged and elderly rural Chinese males.Methods:A total of 965 men completed a questionnaire and underwent a detailed physical examination.The Aging Males'Symptoms(AMS)scale was used to assess SLOH,and the International Prostate Symptom Score(IPSS)questionnaire was used to assess LUTS.Serum reproductive hormone levels of testosterone,sex hormone-binding globulin(SHBG)and luteinizing hormone(LH)were measured.Results:A total of 965 males(mean age:56.34±8.85,range:40-80 years)were recruited for the present study.A total of 20.93%(202/965)were diagnosed with SLOH.A total of 93.16%(899/965)had mild LUTS,5.18%(50/965)had moderate LUTS,and 1.66%(16/965)had severe LUTS.Among SLOH patients,13.40%(27/202)and 3.90%(8/202)had moderate and severe LUTS,respectively.Patients with severe LUTS had increased SHBG and LH compared with those with mild and moderate LUTS(P<0.01).Correlation analysis revealed that the AMS total score was positively correlated with the IPSS score(P<0.05).The prevalence of SLOH was significantly increased with LUTS severity In addition to the known effect of age,the results of mutiple regression analysis also showed that serum LH or SHBG appeared to have a weak link with SLOH and LUTS that requires etiological and biological clarification in our future study.Conclusion:In this cross-sectional analysis of SLOH and LUTS,LUTS severity was significantly associated with hypogonadism symptoms.Additionally,the prevalence of SLOH advanced with increasing LUTS severity.Serum SHBG or LH showed a positive correlation with SLOH and LUTS.
基金This study was funded by the National Science and Technology R&D Programme,as a part of the 12^(th) Five_Year Plan of China(No.2012BAI32B08).
文摘Objective:This large-scale cross-sectional study aims to identify the characteristics of and risk factors associated with sexual repression among internal migrants in China.Methods:Between August 2013 and August 2015,a total of 8,669 internal migrants from four major cities in China(Beijing,Shanghai,Chengdu,and Chongqing)voluntarily participated in our study.They were interviewed,and the data on their demographic information,occupation,and sexual activities were collected.The Chi-square test and multiple logistic regressions were conducted to identify significant associations.A stepwise method was adopted for the selection of variables.Results:There were 3,597(41.49%)males and 5,072(58.51%)females in total.A higher percentage of males reported that they felt sexual repression compared to females(14.43%vs.9.21%).After adjusting for other covariates,the consequence was showed that male migrants working for more than 5 days were more likely to report sexual repression(odds ratio[OR]=1.40,P<0.05).Living in a collective dormitory with others was also a risk factor for male migrants.The longer males spent with their partners,the less sexual repression occurred(OR=0.94,P<0.05).Similarly,agricultural household registration status and working for more than 5 days increased the risk for sexual repression among female migrants(OR=1.41 and OR=1.46,respectively,P<0.05).Frequent and constructive communication also protected females against sexual repression(P<0.05).Well-educated females experienced relatively less sexual repression when compared to their counterparts with less education(P<0.05).Conclusions:Sexual repression was significantly associated with a few demographic,occupational,and sexual risk factors.Meaningful differences have been identified between male and female migrants.More effective intervention programs such as safeguard measures and welfare policies should be designed and implemented for a majority of female migrants and for those with agricultural household registration status.
基金This study was supported by the National Natural Science Foundation of China(NSFC)(No.81300552,92057119,31970798)the Innovation-oriented Science and Technology Grant from NPFPC Key Laboratory of Reproduction Regulation(CX2017-2)+1 种基金the Program for Zhuoxue of Fudan University(JIF157602)the Support Project for Original Personalized Research of Fudan University.
文摘Objective::The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus.The interaction between decidualγδT cells and trophoblasts plays a pivotal role during successful pregnancy;however,their physiological functions in early-term human pregnancy are still not completely illustrated.This study was undertaken to illustrate the functional roles of CXCL16/CXCR6 to prevent pregnancy loss via the crosstalk between decidualγδT cells and HTR8/SVneo trophoblast cells.Methods::The percentile of CXCR6+γδT cells in the peripheral blood from normal female and recurrent spontaneous abortion(RSA)patients was analyzed by flow cytometry.The expression of CXCR6 was detected in decidual immune cells via flow cytometry,and the expression of CXCL16 was analyzed in HTR8/SVneo trophoblast cells and lentivirus(LV)-HTR8/SVneo trophoblast cells via enzyme-linked immunosorbent assay.Reverse transcriptase-polymerase chain reaction was used to verify the expression of the CXCL16 gene in LV-HTR8/SVneo trophoblast cells.Expression of granzyme B and cytokines and proliferation of decidualγδT cocultured with HTR8/SVneo trophoblast cells were analyzed by flow cytometry.Invasion of HTR8/SVneo trophoblast cells was assessed via Matrigel transwell assay.Adoptive transfer was induced in vivo further to illustrate that the normal expression of CXCL16/CXCR6 could prevent pregnancy loss.Results::The percentile of CXCR6+γδT cells in the peripheral blood from RSA patients was lower than normal pregnancies.The expression of CXCR6 was highest in the decidualγδT cells among decidual immune cells,and the expression of CXCL16 increased as the amount of HTR8/SVneo trophoblast cells increased.Expression of granzyme B in the decidualγδT cells was downregulated by cocultured with HTR8/SVneo cells dependent of CXCL16,and HTR8/SVneo trophoblast cells induced the Th2 cytokines production in the decidualγδT cells.Both the expression of CXCR6 in the decidualγδT cells and proliferation of the decidualγδT cells were promoted by HTR8/SVneo trophoblast cells.On the other hand,decidualγδT cells enhanced the invasion of HTR8/SVneo trophoblast cells and thus promoted embryo implantation.In vivo study was taken further and shown that low expression of CXCL16/CXCR6 results in pregnancy loss because of dialog disorder between decidualγδT cells and trophoblasts.Conclusions::Low expression of CXCL16/CXCR6 results in pregnancy loss because of the dialog disorder between decidualγδT cells and trophoblasts,and it showed a light on the effective strategy of adoptive transfer of CXCR6+γδT cells on the treatment of RSA.This observation provides a scientific basis on which a potential strategy can be applied to the early-detect and treatment of RSA.
文摘Pregnancy is a complicated process with intricate cell-to-cell crosstalk and immune regulation.Decidual natural killer(NK)cells account for 50%-70% of decidual immune cells in early pregnancy,suggesting that they play important roles in various events,such as embryo implantation and vascular remodeling.Many studies have shown that decidual NK cells interact with other cells either through direct contact or the secretion factors such as cytokines and chemokines.Hence,this review aimed to present the phenotypic characteristics,classification,and functions of decidual NK cells at the maternal-fetal interface during pregnancy.
基金supported by the National Basic Research Program of China(2017YFC1001403)the National Nature Science Foundation of China(31970859,81630036,and 91542116)+2 种基金the Innovation-oriented Science and Technology Grant from the NHC Key Laboratory of Reproduction Regulation(CX2017-2)The Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine Supported by Ferring Pharmaceuticals and the Chinese Academy of Sciences(FIRMX200504)the funding for the Innovative Research Team of High-level Local Universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality(ZDSYS14005).
文摘In early pregnancy,the decidua is populated by a large number of natural killer cells(NKs),most of which are CD56bright with a strong capacity to secrete cytokines,differing from peripheral and cord blood NK cells(pNKs and cNKs).1,2,3 It is generally believed that uterine NKs are recruited from the peripheral blood and are further educated to develop a decidual NK cell(dNK)-like phenotype in the microenvironment at the maternal-fetal interface.4 However,the defined mechanisms involved in this education remain unclear.
