Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutan...Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutaneous electrical acupoint stimulation （TEAS）, become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of ENTEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/rEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome （PCOS）, pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligosperrnia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.展开更多
Based on the macroanalysis of the unbalanced development of the"demand side"and the"supply side"of clinical medicine in China,this paper elucidates the stakeholders,resources,and ecosystem of the s...Based on the macroanalysis of the unbalanced development of the"demand side"and the"supply side"of clinical medicine in China,this paper elucidates the stakeholders,resources,and ecosystem of the strategic scientific and technological capacity-building and calls for a larger coverage,smoother supply chain,and more sustainable ecosystem to ensure the development of clinical medicine.Furthermore,focusing on the establishment and development of clinical reproductive health in China,the authors introduce the strategic scientific and technological capacity-building of reproductive medicine in Peking University Third Hospital,with an attempt to inform similar efforts in other fields and even the whole clinical medicine in China.展开更多
Spermatogonial stem cells （SSCs）, also known as male germline stem cells, are a small subpopulation of type A spermatogonia with the potential of self-renewal to maintain stem cell pool and differentiation into sper...Spermatogonial stem cells （SSCs）, also known as male germline stem cells, are a small subpopulation of type A spermatogonia with the potential of self-renewal to maintain stem cell pool and differentiation into spermatids in mammalian testis. SSCs are previously regarded as the unipotent stem cells since they can only give rise to sperm within the seminiferous tubules. However, this concept has recently been challenged because numerous studies have demonstrated that SSCs cultured with growth factors can acquire pluripotency to become embryonic stem-like cells. The in vivo and in vitro studies from peers and us have clearly revealed that SSCs can directly transdifferentiate into morphologic, phenotypic, and functional cells of other lineages. Direct conversion to the cells of other tissues has important significance for regenerative medicine. SSCs from azoospermia patients could be induced to differentiate into spermatids with fertilization and developmental potentials. As such, SSCs could have significant applications in both reproductive and regenerative medicine due to their unique and great potentials. In this review, we address the important plasticity of SSCs, with focuses on their self-renewal, differentiation, dedifferentiation, transdifferentiation, and translational medicine studies.展开更多
There has been a very rapid development in the area of preimplantation genetic testing(PGT)since the first baby applied PGT technology in the world was born in the last 30 years.As an alternative treatment of prenatal...There has been a very rapid development in the area of preimplantation genetic testing(PGT)since the first baby applied PGT technology in the world was born in the last 30 years.As an alternative treatment of prenatal diagnosis,the transfer of the fetus with normal testing result has benefited many families.PGT is mainly classified into PGT for aneuploidies(PGT-A),PGT for chromosomal structural rearrangement(PGT-SR),and PGT for monogenic/single-gene defects(PGT-M).Here,we reviewed the application,development,limitations,and challenges of the current PGT in reproductive medicine.展开更多
Single-cell multi-omics sequencing has greatly accelerated reproductive research in recent years,and the data are continually growing.However,utilizing these data resources is challenging for wet-lab researchers.A com...Single-cell multi-omics sequencing has greatly accelerated reproductive research in recent years,and the data are continually growing.However,utilizing these data resources is challenging for wet-lab researchers.A comprehensive platform for exploring single-cell multi-omics data related to reproduction is urgently needed.Here,we introduce the single-cell multi-omics atlas of reproduction(SMARTdb),an integrative and user-friendly platform for exploring molecular dynamics of reproductive development,aging,and disease,which covers multi-omics,multi-species,and multi-stage data.We curated and analyzed single-cell transcriptomic and epigenomic data of over 2.0 million cells from 6 species across the entire lifespan.A series of powerful functionalities are provided,such as“Query gene expression”,“DIY expression plot”,“DNA methylation plot”,and“Epigenome browser”.With SMARTdb,we found that the male germ cell-specific expression pattern of RPL39L and RPL10L is conserved between human and other model animals.Moreover,DNA hypomethylation and open chromatin may collectively regulate the specific expression pattern of RPL39L in both male and female germ cells.In summary,SMARTdb is a powerful platform for convenient data mining and gaining novel insights into reproductive development,aging,and disease.SMARTdb is publicly available at https://smart-db.cn.展开更多
Reproductive health encompasses the entire spectrum of reproductive processes and functions throughout a person’s life,playing a vital role in the harmonious development of populations,economies,and societies.This cr...Reproductive health encompasses the entire spectrum of reproductive processes and functions throughout a person’s life,playing a vital role in the harmonious development of populations,economies,and societies.This critical aspect has garnered increasing global attention.Ensuring sexual and reproductive health stands as a fundamental step toward achieving the United Nations Sustainable Development Goal(SDG)by 2030[1].Despite extensive efforts,both China and the world at large confront a multitude of reproductive challenges.These challenges encompass declining fertility rates[2,3],high prevalence of birth defects,and the presence of various reproductive diseases that threaten fetal development.These issues contribute to emotional distress,relationship problems,social stigmatization,and an increased risk of adult-onset diseases,imposing a significant burden on individuals and society[2].In the realm of human reproductive health research,epidemiological approaches have played a pivotal role.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
Collagen-based biomaterials(CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines.In recent years,owing to advancements ...Collagen-based biomaterials(CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines.In recent years,owing to advancements in developmental biology techniq ues,this superior biomaterial has seen increasing utilization in 3D in vitro tissue culture.Three-dimensional cell cultures,often referred to as organoids,have emerged in response to technological advancements in biomaterials and the growing need in the field of medical research.They serve as important models for simulating normal physiological activities in vivo,addressing limitations in experimental material sources,and resolving ethical issues.In this review,we discuss the material characteristics of CBBs commonly used for organoid culture,integrating aspects such as Matrigel and decellularized ECM as culture matrices.We also analyzed the development prospects and directions of various materials in the context of biology,clinical medicine,and partic ularly reproductive medicine.Currently,despite the FDA approval and clinical research incorporating numerous CBBs,existing challenges in multiple studies indicate a significant unmet need in the development of key tissue models for both medical research and clinical applications.In summary,CBBs are swiftly broadening their applicability in the realms of organoid nature and medical research,serving as a versatile and high-performing material for 3D in vitro tissue culture.展开更多
Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian resto...Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian restoration.In this study,a subcutaneous implantation system using gelatin methacryloyl(GelMA)hydrogel embedded with ICA was developed to restore ovarian function in aged female mice.Mice were assigned to receive subcutaneous implantation of GelMA alone(GelMA group),GelMA containing ICA(GelMA/ICA group),or a sham operation.Ovarian morphology,serum hormone levels,follicle counts across developmental stages,and reproductive outcomes were evaluated.In vitro fertilization(IVF)and embryo culture assays were performed to assess oocyte developmental potential,while a 10 day natural mating trial was conducted to determine fertility restoration.RNA sequencing(RNA-seq)and RT-qPCR were performed to elucidate the underlying molecular mechanisms.Results showed that GelMA/ICA treatment significantly increased ovarian index(0.19±0.01 vs.0.13±0.01,P<0.0001)and follicle numbers at all developmental stages,including primordial(383.33±151.65 vs.107.14±32.26,P<0.0001),primary(203.33±83.22 vs.91.43±27.04,P=0.003),and secondary follicles(154.17±52.00 vs.59.28±20.50,P=0.029)compared to the sham controls.Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone(FSH,11.97±3.53 vs.53.10±17.89 ng/mL,P=0.0008),accompanied by elevated anti-Müllerian hormone(AMH,22.97±2.26 vs.5.54±1.56 ng/mL,P<0.0001)and estradiol(E2,315.30±37.62 vs.168.5±14.78 pg/mL,P<0.0001).Oocyte yield and developmental potential improved significantly,as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs.4.83±4.79,P=0.0002),and higher proportions of two-cell(85.90%±6.16%vs.50.00%±10.00%,P=0.0009),four-cell(81.67%±9.76%vs.50.00%±10.00%,P=0.0061),and blastocyst stage embryos(64.25%±10.55%vs.23.33%±15.28%,P=0.0067).Live birth numbers were significantly increased following GelMA/ICA treatment(6.90±3.21 vs.1.72±2.05,P=0.0001).Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3),lipid storage(Soat2,Plin4),oocyte maturation(Oosp2),and cytokine secretion(Cxcl12).Collectively,these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice,offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.展开更多
Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its s...Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1].展开更多
V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating ene...V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.展开更多
Prenatal maternal psychological distress,particularly depression,has been increasingly recognized as a factor that influences fetal growth;however,its impact on early childhood development remains less well understood...Prenatal maternal psychological distress,particularly depression,has been increasingly recognized as a factor that influences fetal growth;however,its impact on early childhood development remains less well understood.The present study investigated the association between prenatal depression and children's growth trajectories,as well as the odds of overweight and obesity from 1 to 36 months,while also accounting for maternal anxiety and stress.We analyzed data from 4710 mother-child dyads in the Jiangsu Birth Cohort,assessing maternal psychological distress across trimesters and categorizing participants into groups with mild,moderate,and severe depressive symptomatology.Children's weight-for-length z-scores(WLZ)were used to assess overweight/obesity prevalence,and growth patterns were identified through trajectory models.The results from the generalized estimating equations analysis showed that greater depressive symptomatology during pregnancy was associated with a 28%to 41%increase in the odds of childhood overweight/obesity across all three trimesters,compared with mild depressive symptomatology.We identified five distinct WLZ growth trajectory patterns,and found that mothers with greater depressive symptomatology were 39%–47%more likely to have children who followed a very-high-stable growth trajectory,compared with mothers with mild depressive symptomatology.These findings highlight the significant impact of prenatal depression on adverse growth patterns and childhood overweight/obesity,underscoring the need for early intervention.展开更多
Varicocele affects approximately 35%-40% of men presenting for an infertility evaluation. There is fair evidence indicating that surgical repair of clinical varicocele improves semen parameters, decreases seminal oxid...Varicocele affects approximately 35%-40% of men presenting for an infertility evaluation. There is fair evidence indicating that surgical repair of clinical varicocele improves semen parameters, decreases seminal oxidative stress and sperm DNA fragmentation, and increases the chances of natural conception. However, it is unclear whether performing varicocelectomy in men with clinical varicocele prior to assisted reproductive technology （ART） improve treatment outcomes. The objective of this study was to evaluate the role of varicocelectomy on ART pregnancy outcomes in nonazoospermic infertile men with clinical varicocele. An electronic search was performed to collect all evidence that fitted our eligibility criteria using the MEDLINE and EMBASE databases until April 2015. Four retrospective studies were included, all of which involved intracytoplasmic sperm injection （ICSI）, and accounted for 870 cycles （438 subjected to ICSI with prior varicocelectomy, and 432 without prior varicocelectomy）. There was a significant increase in the clinical pregnancy rates （OR = 1.59, 95% CI. 1.19-2.12, 12 = 25%） and live birth rates （OR = 2.17, 95% CI： 1,55-3.06, I^2 = 0%） in the varicocelectomy group compared to the group subjected to ICSI without previous varicocelectomy. Our results indicate that performing varicocelectomy in patients with clinical varicocele prior to ICSI is associated with improved pregnancy outcomes.展开更多
We assessed the rates of sperm retrieval and intracytoplasmic sperm injection outcomes, including the neonatal profile of infants conceived, in men with testicular failure. Three-hundred and sixty-five men with testic...We assessed the rates of sperm retrieval and intracytoplasmic sperm injection outcomes, including the neonatal profile of infants conceived, in men with testicular failure. Three-hundred and sixty-five men with testicular failure who underwent micro-dissection testicular sperm extraction were included in this study. We compared their outcomes with 40 men with testicular failure who used donor sperm for injections due to failed retrieval, and 146 men with obstructive azoospermia who underwent percutaneous sperm retrieval. The retrieval rate in testicular failure was 41.4%, and the results were lower than the obstructed azoospermia （100%; adjusted odds ratio： 0.033; 95% Ch 0.007-0.164; P 〈 0.001）. Live birth rates after sperm injections were lower in men with testicular failure （19.9%） compared with donor sperm （37.5%; adjusted OR： 0.377 （95% Ch 0.233-0.609, P 〈 0.001）） and obstructive azoospermia （34.2%; adjusted OR： 0.403 （95% CI： 0.241-0.676, P= 0.001）. Newborn parameters of infants conceived were not significantly different among the groups. We concluded that the chances of obtaining sperm on retrieval and achieving a live birth after intracytoplasmic sperm injection （ICSI） are reduced in men with testicular failure. The profile of infants conceived after sperm injection does not seem to be negatively affected by testicular failure.展开更多
Aim： To promote the provision of reproductive health services to young people by exploring the attitudes and perceptions of university students in Shanghai, China, toward reproductive health. Methods： From July 2004...Aim： To promote the provision of reproductive health services to young people by exploring the attitudes and perceptions of university students in Shanghai, China, toward reproductive health. Methods： From July 2004 to May 2006, 5 243 students from 14 universities in Shanghai took part in our survey. Topics covered the demands of reproductive health-care services, attitudes towards and experience with sex, exposure to pornographic material, and knowledge on sexual health and sexually transmitted infections （STIs）/AIDS. Results： Of the 5 067 students who provided valid answer sheets, 50.05% were female and 49.95% were male, 14.86% were medical students, and 85.14% had non-medical backgrounds. A total of 38.4% of respondents had received reproductive health education previously. The majority of students supported school-based reproductive health education, and also acquired information about sex predominantly from books, schoolmates, and the Internet. Premarital sexual behavior was opposed by 17.7% of survey participants, and 37.5% could identify all the three types of STIs listed in the questionnaire. Although 83.7% knew how HIV is transmitted, only 55.7% knew when to use a condom and 57.8% knew that the use of condoms could reduce the risk of HIV infection. Conclusion： The reproductive health service is lagging behind current attitudes and demands of university students. Although students＇ attitudes towards sexual matters are liberal, their knowledge about reproductive health and STIs/AIDS is still limited. It is therefore necessary to provide effective and confidential reproductive health services to young people.展开更多
Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consum...Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.展开更多
Sperm banking can preserve male fertility effectively, but the current conditions of sperm cryopreservation in China have not been investigated. This retrospective investigation was based on data collected at multiple...Sperm banking can preserve male fertility effectively, but the current conditions of sperm cryopreservation in China have not been investigated. This retrospective investigation was based on data collected at multiple centres in China from January 2003 to December 2008. The collected data included urogenital history, indication for cryopreservation, semen parameters, use rate, type of assisted reproductive technique （ART） treatment and pregnancy outcome. The study population included 1 548 males who had banked their semen during the study period at one of the clinics indicated above. Approximately 1.9% （30/1 548） of the cryopreserved semen samples were collected from cancer patients; about 88.8% （1 374/1 548） of the patients had banked their semen for ART and 8.6% （134/1 548） had a male infertility disease （such as anejaculation, severe oligozoospermia and obstructive azoospermia）. The total use rate of cryopreserved semen was 22.7% （352/1 548）, with 119 live births. The cancer group use rate was 6.7% （2/30）, with one live birth by intracytoplasmic single sperm injection （ICSI）. The ART group use rate was 23.2% （319/1 374）, with 106 live births. The reproductive disease group use rate was 23.1% （31/134）, with 12 live births. The semen parameters in each category varied; the cancer patient and infertility disease groups had poor semen quality. In vitro fertilization （IVF） and ICSI were the most common ART treatments for cryopreserved sperm. Semen cryopreservation as a salvage method is effective, but in many conditions it is underutilized, especially in cancer patients. Lack of awareness, urgency of cancer treatment and financial constraints are the main causes of the low access rate. The concept of fertility preservation should be popularized to make better use of this medical service in China.展开更多
Bisphenol A （BPA）, an estrogenic chemical, has been shown to reduce sperm count; however, the underlying mechanisms remain unknown. Herein, we show that oral administration of BPA （2 μg/kg） for consecutive 14 day...Bisphenol A （BPA）, an estrogenic chemical, has been shown to reduce sperm count; however, the underlying mechanisms remain unknown. Herein, we show that oral administration of BPA （2 μg/kg） for consecutive 14 days in adult rats （BPA rats） significantly reduced the sperm count and the number of germ cells compared to controls. The serum levels of testosterone and follicle-stimulating hormone （FSH）, as well as the level of GnRH mRNA in BPA rats were lower than those of control rats. Testosterone treatment could partially rescue the reduction of germ cells in BPA rats. Notably, the number of apoptotic germ cells was significantly increased in BPA rats, which was insensitive to testosterone. Furthermore, the levels of Fas, FasL and caspase-3 mRNA in the testicle of BPA rats were increased in comparison with controls. These results indicate that exposure to a low dose of BPA impairs spermatogenesis through decreasing reproductive hormones and activating the Fas/FasL signaling pathway.展开更多
Proper reprogramming of parental DNA methylomes is essential for mammalian embryonic development. However, it is unknown whether abnormal methylome reprogramming occurs and is associated with the failure of embryonic ...Proper reprogramming of parental DNA methylomes is essential for mammalian embryonic development. However, it is unknown whether abnormal methylome reprogramming occurs and is associated with the failure of embryonic development. Here we analyzed the DNA methylomes of 57 blastocysts and 29 trophectoderm samples with different morphological grades during assisted reproductive technology （ART） practices. Our data reveal that the global methylation levels of high-quality blastocysts are similar （0.30 ± 0.02, mean ± SD）, while the methylation levels of low-quality blastocysts are divergent and away from those of high-quality blastocysts. The proportion of blastocysts with a methylation level falling within the range of 0.30± 0.02 in different grades correlates with the live birth rate for that grade. Moreover, abnormal methylated regions are associated with the failure of embryonic development. Furthermore, we can use the methylation data of cells biopsied from trophectoderm to predict the blastocyst methylation level as well as to detect the aneuploidy of the blastocysts. Our data indicate that global abnormal methylome reprogramming often occurs in human embryos, and suggest that DNA methylome is a potential biomarker in blastocyst selection in ART.展开更多
The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Who...The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.展开更多
基金Project supported by the Special Research Fund for the Public Welfare Industry of Health of China(No.201302013)
文摘Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutaneous electrical acupoint stimulation （TEAS）, become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of ENTEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/rEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome （PCOS）, pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligosperrnia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.
文摘Based on the macroanalysis of the unbalanced development of the"demand side"and the"supply side"of clinical medicine in China,this paper elucidates the stakeholders,resources,and ecosystem of the strategic scientific and technological capacity-building and calls for a larger coverage,smoother supply chain,and more sustainable ecosystem to ensure the development of clinical medicine.Furthermore,focusing on the establishment and development of clinical reproductive health in China,the authors introduce the strategic scientific and technological capacity-building of reproductive medicine in Peking University Third Hospital,with an attempt to inform similar efforts in other fields and even the whole clinical medicine in China.
文摘Spermatogonial stem cells （SSCs）, also known as male germline stem cells, are a small subpopulation of type A spermatogonia with the potential of self-renewal to maintain stem cell pool and differentiation into spermatids in mammalian testis. SSCs are previously regarded as the unipotent stem cells since they can only give rise to sperm within the seminiferous tubules. However, this concept has recently been challenged because numerous studies have demonstrated that SSCs cultured with growth factors can acquire pluripotency to become embryonic stem-like cells. The in vivo and in vitro studies from peers and us have clearly revealed that SSCs can directly transdifferentiate into morphologic, phenotypic, and functional cells of other lineages. Direct conversion to the cells of other tissues has important significance for regenerative medicine. SSCs from azoospermia patients could be induced to differentiate into spermatids with fertilization and developmental potentials. As such, SSCs could have significant applications in both reproductive and regenerative medicine due to their unique and great potentials. In this review, we address the important plasticity of SSCs, with focuses on their self-renewal, differentiation, dedifferentiation, transdifferentiation, and translational medicine studies.
文摘There has been a very rapid development in the area of preimplantation genetic testing(PGT)since the first baby applied PGT technology in the world was born in the last 30 years.As an alternative treatment of prenatal diagnosis,the transfer of the fetus with normal testing result has benefited many families.PGT is mainly classified into PGT for aneuploidies(PGT-A),PGT for chromosomal structural rearrangement(PGT-SR),and PGT for monogenic/single-gene defects(PGT-M).Here,we reviewed the application,development,limitations,and challenges of the current PGT in reproductive medicine.
基金supported by the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(Grant No.2020QNRC001)the research start-up funding from Nanjing Medical University,China(Grant No.KY116RC20200007).
文摘Single-cell multi-omics sequencing has greatly accelerated reproductive research in recent years,and the data are continually growing.However,utilizing these data resources is challenging for wet-lab researchers.A comprehensive platform for exploring single-cell multi-omics data related to reproduction is urgently needed.Here,we introduce the single-cell multi-omics atlas of reproduction(SMARTdb),an integrative and user-friendly platform for exploring molecular dynamics of reproductive development,aging,and disease,which covers multi-omics,multi-species,and multi-stage data.We curated and analyzed single-cell transcriptomic and epigenomic data of over 2.0 million cells from 6 species across the entire lifespan.A series of powerful functionalities are provided,such as“Query gene expression”,“DIY expression plot”,“DNA methylation plot”,and“Epigenome browser”.With SMARTdb,we found that the male germ cell-specific expression pattern of RPL39L and RPL10L is conserved between human and other model animals.Moreover,DNA hypomethylation and open chromatin may collectively regulate the specific expression pattern of RPL39L in both male and female germ cells.In summary,SMARTdb is a powerful platform for convenient data mining and gaining novel insights into reproductive development,aging,and disease.SMARTdb is publicly available at https://smart-db.cn.
文摘Reproductive health encompasses the entire spectrum of reproductive processes and functions throughout a person’s life,playing a vital role in the harmonious development of populations,economies,and societies.This critical aspect has garnered increasing global attention.Ensuring sexual and reproductive health stands as a fundamental step toward achieving the United Nations Sustainable Development Goal(SDG)by 2030[1].Despite extensive efforts,both China and the world at large confront a multitude of reproductive challenges.These challenges encompass declining fertility rates[2,3],high prevalence of birth defects,and the presence of various reproductive diseases that threaten fetal development.These issues contribute to emotional distress,relationship problems,social stigmatization,and an increased risk of adult-onset diseases,imposing a significant burden on individuals and society[2].In the realm of human reproductive health research,epidemiological approaches have played a pivotal role.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
基金supported by funding from the projects of the National Natural Science Foundation of China(Y.Z.,Grant No.82001496)Sichuan Science and Technology Program(Sichuan Natural Science Foundation for Youth,China,NO.2022NSFSC1281)Sichuan Medical Association Foundation(China,NO.S21006)
文摘Collagen-based biomaterials(CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines.In recent years,owing to advancements in developmental biology techniq ues,this superior biomaterial has seen increasing utilization in 3D in vitro tissue culture.Three-dimensional cell cultures,often referred to as organoids,have emerged in response to technological advancements in biomaterials and the growing need in the field of medical research.They serve as important models for simulating normal physiological activities in vivo,addressing limitations in experimental material sources,and resolving ethical issues.In this review,we discuss the material characteristics of CBBs commonly used for organoid culture,integrating aspects such as Matrigel and decellularized ECM as culture matrices.We also analyzed the development prospects and directions of various materials in the context of biology,clinical medicine,and partic ularly reproductive medicine.Currently,despite the FDA approval and clinical research incorporating numerous CBBs,existing challenges in multiple studies indicate a significant unmet need in the development of key tissue models for both medical research and clinical applications.In summary,CBBs are swiftly broadening their applicability in the realms of organoid nature and medical research,serving as a versatile and high-performing material for 3D in vitro tissue culture.
基金supported by the National Natural Science Foundation of China(82271671)Nanjing Drum Tower Hospital Academic Innovation Peak Fund(2024-DF-02)+4 种基金Clinical Trials from Nanjing Drum Tower Hospital(2023-LCYJ-MS-05)Nanjing International Science and Technology Cooperation Program(202201027)to L.D.Research Project of State Key Laboratory of Reproductive Medicine and Offspring Health(SKLRM-2022D2)Changzhou Medical Center of Nanjing Medical University(CMCM202203)Clinical Trials from Nanjing Drum Tower Hospital(2022-LCYJ-ZD-02)to H.S.
文摘Ovarian aging is characterized by a progressive decline in oocyte quality and quantity with age.Icariin(ICA),a flavonoid compound derived from Epimedium species,has demonstrated potential as an agent for ovarian restoration.In this study,a subcutaneous implantation system using gelatin methacryloyl(GelMA)hydrogel embedded with ICA was developed to restore ovarian function in aged female mice.Mice were assigned to receive subcutaneous implantation of GelMA alone(GelMA group),GelMA containing ICA(GelMA/ICA group),or a sham operation.Ovarian morphology,serum hormone levels,follicle counts across developmental stages,and reproductive outcomes were evaluated.In vitro fertilization(IVF)and embryo culture assays were performed to assess oocyte developmental potential,while a 10 day natural mating trial was conducted to determine fertility restoration.RNA sequencing(RNA-seq)and RT-qPCR were performed to elucidate the underlying molecular mechanisms.Results showed that GelMA/ICA treatment significantly increased ovarian index(0.19±0.01 vs.0.13±0.01,P<0.0001)and follicle numbers at all developmental stages,including primordial(383.33±151.65 vs.107.14±32.26,P<0.0001),primary(203.33±83.22 vs.91.43±27.04,P=0.003),and secondary follicles(154.17±52.00 vs.59.28±20.50,P=0.029)compared to the sham controls.Hormonal analyses revealed a significant reduction in serum follicle-stimulating hormone(FSH,11.97±3.53 vs.53.10±17.89 ng/mL,P=0.0008),accompanied by elevated anti-Müllerian hormone(AMH,22.97±2.26 vs.5.54±1.56 ng/mL,P<0.0001)and estradiol(E2,315.30±37.62 vs.168.5±14.78 pg/mL,P<0.0001).Oocyte yield and developmental potential improved significantly,as reflected by the increased number of superovulated MII oocytes(17.83±5.15 vs.4.83±4.79,P=0.0002),and higher proportions of two-cell(85.90%±6.16%vs.50.00%±10.00%,P=0.0009),four-cell(81.67%±9.76%vs.50.00%±10.00%,P=0.0061),and blastocyst stage embryos(64.25%±10.55%vs.23.33%±15.28%,P=0.0067).Live birth numbers were significantly increased following GelMA/ICA treatment(6.90±3.21 vs.1.72±2.05,P=0.0001).Transcriptomic analysis revealed up-regulation of genes associated with cytoskeletal organization(Vil1,Tubb3),lipid storage(Soat2,Plin4),oocyte maturation(Oosp2),and cytokine secretion(Cxcl12).Collectively,these findings suggest that GelMA/ICA hydrogels effectively reverse key hallmarks of ovarian aging and restore reproductive function in aged mice,offering a promising platform for fertility preservation and a novel therapeutic for future investigations into ovarian aging.
文摘Dear Editor,Lymphocyte activation gene 3(LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex classⅡ(MHCⅡ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1].
基金support from various sources,including the National Natural Science Foundation of China(Grant Nos.81570774,82070872,92049118,and 82370854)the Junior Thousand Talents Program of China,and the Nanjing Medical University Startup Fund(All awarded to J.L.)support provided by Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(Grant No.JSSCTD2021)(All awarded to J.L.).
文摘V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.
基金supported by the National Natural Science Foundation of China(Grant No.82373581 to Yuan Lin).
文摘Prenatal maternal psychological distress,particularly depression,has been increasingly recognized as a factor that influences fetal growth;however,its impact on early childhood development remains less well understood.The present study investigated the association between prenatal depression and children's growth trajectories,as well as the odds of overweight and obesity from 1 to 36 months,while also accounting for maternal anxiety and stress.We analyzed data from 4710 mother-child dyads in the Jiangsu Birth Cohort,assessing maternal psychological distress across trimesters and categorizing participants into groups with mild,moderate,and severe depressive symptomatology.Children's weight-for-length z-scores(WLZ)were used to assess overweight/obesity prevalence,and growth patterns were identified through trajectory models.The results from the generalized estimating equations analysis showed that greater depressive symptomatology during pregnancy was associated with a 28%to 41%increase in the odds of childhood overweight/obesity across all three trimesters,compared with mild depressive symptomatology.We identified five distinct WLZ growth trajectory patterns,and found that mothers with greater depressive symptomatology were 39%–47%more likely to have children who followed a very-high-stable growth trajectory,compared with mothers with mild depressive symptomatology.These findings highlight the significant impact of prenatal depression on adverse growth patterns and childhood overweight/obesity,underscoring the need for early intervention.
文摘Varicocele affects approximately 35%-40% of men presenting for an infertility evaluation. There is fair evidence indicating that surgical repair of clinical varicocele improves semen parameters, decreases seminal oxidative stress and sperm DNA fragmentation, and increases the chances of natural conception. However, it is unclear whether performing varicocelectomy in men with clinical varicocele prior to assisted reproductive technology （ART） improve treatment outcomes. The objective of this study was to evaluate the role of varicocelectomy on ART pregnancy outcomes in nonazoospermic infertile men with clinical varicocele. An electronic search was performed to collect all evidence that fitted our eligibility criteria using the MEDLINE and EMBASE databases until April 2015. Four retrospective studies were included, all of which involved intracytoplasmic sperm injection （ICSI）, and accounted for 870 cycles （438 subjected to ICSI with prior varicocelectomy, and 432 without prior varicocelectomy）. There was a significant increase in the clinical pregnancy rates （OR = 1.59, 95% CI. 1.19-2.12, 12 = 25%） and live birth rates （OR = 2.17, 95% CI： 1,55-3.06, I^2 = 0%） in the varicocelectomy group compared to the group subjected to ICSI without previous varicocelectomy. Our results indicate that performing varicocelectomy in patients with clinical varicocele prior to ICSI is associated with improved pregnancy outcomes.
文摘We assessed the rates of sperm retrieval and intracytoplasmic sperm injection outcomes, including the neonatal profile of infants conceived, in men with testicular failure. Three-hundred and sixty-five men with testicular failure who underwent micro-dissection testicular sperm extraction were included in this study. We compared their outcomes with 40 men with testicular failure who used donor sperm for injections due to failed retrieval, and 146 men with obstructive azoospermia who underwent percutaneous sperm retrieval. The retrieval rate in testicular failure was 41.4%, and the results were lower than the obstructed azoospermia （100%; adjusted odds ratio： 0.033; 95% Ch 0.007-0.164; P 〈 0.001）. Live birth rates after sperm injections were lower in men with testicular failure （19.9%） compared with donor sperm （37.5%; adjusted OR： 0.377 （95% Ch 0.233-0.609, P 〈 0.001）） and obstructive azoospermia （34.2%; adjusted OR： 0.403 （95% CI： 0.241-0.676, P= 0.001）. Newborn parameters of infants conceived were not significantly different among the groups. We concluded that the chances of obtaining sperm on retrieval and achieving a live birth after intracytoplasmic sperm injection （ICSI） are reduced in men with testicular failure. The profile of infants conceived after sperm injection does not seem to be negatively affected by testicular failure.
文摘Aim： To promote the provision of reproductive health services to young people by exploring the attitudes and perceptions of university students in Shanghai, China, toward reproductive health. Methods： From July 2004 to May 2006, 5 243 students from 14 universities in Shanghai took part in our survey. Topics covered the demands of reproductive health-care services, attitudes towards and experience with sex, exposure to pornographic material, and knowledge on sexual health and sexually transmitted infections （STIs）/AIDS. Results： Of the 5 067 students who provided valid answer sheets, 50.05% were female and 49.95% were male, 14.86% were medical students, and 85.14% had non-medical backgrounds. A total of 38.4% of respondents had received reproductive health education previously. The majority of students supported school-based reproductive health education, and also acquired information about sex predominantly from books, schoolmates, and the Internet. Premarital sexual behavior was opposed by 17.7% of survey participants, and 37.5% could identify all the three types of STIs listed in the questionnaire. Although 83.7% knew how HIV is transmitted, only 55.7% knew when to use a condom and 57.8% knew that the use of condoms could reduce the risk of HIV infection. Conclusion： The reproductive health service is lagging behind current attitudes and demands of university students. Although students＇ attitudes towards sexual matters are liberal, their knowledge about reproductive health and STIs/AIDS is still limited. It is therefore necessary to provide effective and confidential reproductive health services to young people.
文摘Environmental contaminants such as persistent organic pollutants （POPs） are man-made bioaccumulative compounds with long half-lives that are found throughout the world as a result of heavy use in a variety of consumer products during the twentieth century. Wildlife and animal studies have long suggested adverse effects of exposure to these compounds on human reproductive health, which, according to the endocrine disrupter hypothesis, are ascribed to the compounds＇ potential to interfere with endocrine signaling, especially when exposure occurs during certain phases of fetal and childhood development. An extensive number of epidemiological studies have addressed the possible effects of exposure to POPs on male reproductive health, but the results are conflicting. Thus far, most studies have focused on investigating exposure and the different reproductive health outcomes during adulthood. Some studies have addressed the potential harmful effects of fetal exposure with respect to malformations at birth and/ or reproductive development, whereas only a few studies have been able to evaluate whether intrauterine exposure to POPs has long-term consequences for male reproductive health with measurable effects on semen quality markers and reproductive hormone levels in adulthood. Humans are not exposed to a single compound at a time, but rather, to a variety of different substances with potential divergent hormonal effects. Hence, how to best analyze epidemiological data on combined exposures remains a significant challenge. This review on POPs will focus on current knowledge regarding the potential effects of exposure to POPs during fetal and childhood life and during adulthood on male reproductive health, including a critical revision of the endocrine disruption hypothesis, a comment on pubertal development as part of reproductive development and a comment on how to account for combined exposures in epidemiological research.
文摘Sperm banking can preserve male fertility effectively, but the current conditions of sperm cryopreservation in China have not been investigated. This retrospective investigation was based on data collected at multiple centres in China from January 2003 to December 2008. The collected data included urogenital history, indication for cryopreservation, semen parameters, use rate, type of assisted reproductive technique （ART） treatment and pregnancy outcome. The study population included 1 548 males who had banked their semen during the study period at one of the clinics indicated above. Approximately 1.9% （30/1 548） of the cryopreserved semen samples were collected from cancer patients; about 88.8% （1 374/1 548） of the patients had banked their semen for ART and 8.6% （134/1 548） had a male infertility disease （such as anejaculation, severe oligozoospermia and obstructive azoospermia）. The total use rate of cryopreserved semen was 22.7% （352/1 548）, with 119 live births. The cancer group use rate was 6.7% （2/30）, with one live birth by intracytoplasmic single sperm injection （ICSI）. The ART group use rate was 23.2% （319/1 374）, with 106 live births. The reproductive disease group use rate was 23.1% （31/134）, with 12 live births. The semen parameters in each category varied; the cancer patient and infertility disease groups had poor semen quality. In vitro fertilization （IVF） and ICSI were the most common ART treatments for cryopreserved sperm. Semen cryopreservation as a salvage method is effective, but in many conditions it is underutilized, especially in cancer patients. Lack of awareness, urgency of cancer treatment and financial constraints are the main causes of the low access rate. The concept of fertility preservation should be popularized to make better use of this medical service in China.
基金supported by grants for Major State Basic Research Development Program of China (Program 973, 2009CB941701) to Ling Chen, 11KJB310003 and 2010NJMUZ26 to Yingchun Li
文摘Bisphenol A （BPA）, an estrogenic chemical, has been shown to reduce sperm count; however, the underlying mechanisms remain unknown. Herein, we show that oral administration of BPA （2 μg/kg） for consecutive 14 days in adult rats （BPA rats） significantly reduced the sperm count and the number of germ cells compared to controls. The serum levels of testosterone and follicle-stimulating hormone （FSH）, as well as the level of GnRH mRNA in BPA rats were lower than those of control rats. Testosterone treatment could partially rescue the reduction of germ cells in BPA rats. Notably, the number of apoptotic germ cells was significantly increased in BPA rats, which was insensitive to testosterone. Furthermore, the levels of Fas, FasL and caspase-3 mRNA in the testicle of BPA rats were increased in comparison with controls. These results indicate that exposure to a low dose of BPA impairs spermatogenesis through decreasing reproductive hormones and activating the Fas/FasL signaling pathway.
基金supported by grants from the CAS Strategic Priority Research Program (XDB13040000)the National Program on Key Basic Research Project (2014CB943203,2015CB856200,2011CB510101 and 2011CB944504)+2 种基金the National Natural Science Foundation of China(Nos.91219104,31425015,31200958,31371521,31230047 and 81370766)the Beijing Nova Program (xxjh2015011)the Zhujiang Science and Technology Star Project of Guangzhou(2012J2200006)
文摘Proper reprogramming of parental DNA methylomes is essential for mammalian embryonic development. However, it is unknown whether abnormal methylome reprogramming occurs and is associated with the failure of embryonic development. Here we analyzed the DNA methylomes of 57 blastocysts and 29 trophectoderm samples with different morphological grades during assisted reproductive technology （ART） practices. Our data reveal that the global methylation levels of high-quality blastocysts are similar （0.30 ± 0.02, mean ± SD）, while the methylation levels of low-quality blastocysts are divergent and away from those of high-quality blastocysts. The proportion of blastocysts with a methylation level falling within the range of 0.30± 0.02 in different grades correlates with the live birth rate for that grade. Moreover, abnormal methylated regions are associated with the failure of embryonic development. Furthermore, we can use the methylation data of cells biopsied from trophectoderm to predict the blastocyst methylation level as well as to detect the aneuploidy of the blastocysts. Our data indicate that global abnormal methylome reprogramming often occurs in human embryos, and suggest that DNA methylome is a potential biomarker in blastocyst selection in ART.
基金supported by the National Natural Science Foundation of China (Nos. 31522034 and 81730038)the National High Technology Research and Development Program Grant (2015AA020407)
文摘The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.
