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
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
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
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
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
At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients be...At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.展开更多
Reproductive aging involves a progressive decline in fertility,particularly in females(Duncan et al.,2018;Gruhn et al.,2019),which is characterized by the decline in the number of follicles and the deterioration of oo...Reproductive aging involves a progressive decline in fertility,particularly in females(Duncan et al.,2018;Gruhn et al.,2019),which is characterized by the decline in the number of follicles and the deterioration of oocyte quality with age(Broekmans et al.,2004).It occurs in mammals and other organisms,including mice,flies,and worms(Tasnin et al.,2021;Toraason et al.,2022;Isola et al.,2024).Multiple factors contribute to reproductive aging,with chromosomal segregation errors among the most important ones.Accurate chromosome segregation requires the completion of chromatin remodeling events during meiotic prophase(Yang et al.,2024).展开更多
Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities...Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
This study primarily aimed to investigate the prevalence of human papillomavirus(HPV)and other common pathogens of sexually transmitted infections(STIs)in spermatozoa of infertile men and their effects on semen parame...This study primarily aimed to investigate the prevalence of human papillomavirus(HPV)and other common pathogens of sexually transmitted infections(STIs)in spermatozoa of infertile men and their effects on semen parameters.These pathogens included Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,Pseudomonas aeruginosa,and Staphylococcus aureus.A total of 1951 men of infertile couples were recruited between 23 March 2023,and 17 May 2023,at the Department of Reproductive Medicine of The First People’s Hospital of Yunnan Province(Kunming,China).Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping.Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs.The overall prevalence of HPV infection was 12.4%.The top five prevalent HPV subtypes were types 56,52,43,16,and 53 among those tested positive for HPV.Other common infections with high prevalence rates were Ureaplasma urealyticum(28.3%),Ureaplasma parvum(20.4%),and Enterococcus faecalis(9.5%).The prevalence rates of HPV coinfection with Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,and Staphylococcus aureus were 24.8%,25.4%,10.6%,6.4%,2.4%,7.9%,5.9%,0.9%,and 1.3%,respectively.The semen volume and total sperm count were greatly decreased by HPV infection alone.Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability.Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters,emphasizing the necessity of semen screening for STIs.展开更多
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.How...Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.展开更多
Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity am...Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity among cancer cells,which exhibit varying degrees of metabolic reprogramming and thus may result in differential contributions to drug resistance.A home-built single-cell quantitative mass spectrometry(MS)platform,which integrates micromanipulation and electro-osmotic sampling,was developed to quantitatively profile the tricarboxylic acid(TCA)cycle metabolites at the single-cell level.Using this platform,the metabolic profiles of drug-sensitive MCF-7 breast cancer cells and their drug-resistant derivative MCF-7/ADR cells were compared.This results revealed a selective upregulation of downstream TCA cycle metabolites includingα-ketoglutarate,succinate,fumarate,and malate in drug-resistant cancer cells,while early TCA metabolites remained largely unchanged.Furthermore,notable variations in the abundance of the metabolites were observed in individual cells.The comparative analysis also revealed that not all MCF-7/ADR cells exhibit the same degree of metabolic deviation from the parental line in the metabolites during resistance acquisition.The observed metabolic profiles indicate enhanced glutaminolysis,altered mitochondrial electron transport chain activity,and increased metabolic flexibility in drug-resistant cancer cells that support their survival under chemotherapeutic stress.The findings further suggest the potential for incorporating cellular metabolic heterogeneity into future drug resistance studies.展开更多
Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stim...Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stimulating hormone(FSH)levels,menstrual disturbance,and estrogen deficiency are the main symptoms of POl(European Society for Human Reproduction et al.,2016).Besides infertility,patients have an increased risk of long-term complications due to the early deficiency of ovarian steroids,such as osteoporosis,cardiovascular disease,and metabolic disorders(lshizuka,2021).Due to the lack of biomarkers for prediction or early diagnosis,most patients are not diagnosed until the failure stage(serum levels of FSH above 25 IU/L and amenorrhea),missing opportunities for intervention.Therefore,developing sensitive biomarkers for diminished ovarian reserves is paramount for timely treatment to improve reproductive outcomes and prevent long-term complications.展开更多
Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty...Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.展开更多
Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques l...Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.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.
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.
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.
基金supported by a grant from the Beijing Municipal NaturalScience Foundation(No.7194332)the Shandong Province Natural ScienceFoundation(No.ZR2022ZD19).
文摘At the end of 2022,the adjustment of the coronavirus disease 2019(COVID-19)pandemic control policy in China resulted in alarge-scale increase in public infection.To compare the fertility parameters of male patients before and after the adjustments ofthe COVID-19 pandemic control policy in China,we collected data on patients’medical histories and laboratory examinations ontheir first visits between June 2022 and March 2023 in five different hospitals.Data were divided into five groups according tothe timeline of the policy adjustment.The data we collected from male patients included semen quality and serum reproductivehormone levels,and intergroup comparisons were made using the Mann–Whitney U and Chi-square tests.In total,16784 casesunderwent regular semen analysis,11180 had sperm morphology assessments,and 7200 had reproductive hormone analyses.Thedata showed declining trends in semen volume,sperm motility,and the progressive sperm motility rate after the policy adjustment.Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate.Sperm morphology analysisshowed increased neck and tail abnormalities after the policy adjustment.No significant change in hormone levels was observed.Following the adjustment of the COVID-19 prevention policy in China,a decline in sperm motility and morphology was observed.This trend may gradually recover over 2 months.After the policy adjustment,reproductive hormone levels were relatively stablethroughout,except for an increase in luteinizing hormone(LH).These changes in semen parameters suggest that the policyadjustment had a short-to medium-term impact on male reproductive function.
基金supported by Jinan Municipal Health Commission Science and Technology Project(2023-2-13 to F.Z.)the Joint Fund of the Natural Science Foundation of Shandong Province(ZR2022LZL005 to X.L.)Postdoctoral Innovation Project of Shandong Province(SDCX-ZG-202201001 to X.L.)。
文摘Reproductive aging involves a progressive decline in fertility,particularly in females(Duncan et al.,2018;Gruhn et al.,2019),which is characterized by the decline in the number of follicles and the deterioration of oocyte quality with age(Broekmans et al.,2004).It occurs in mammals and other organisms,including mice,flies,and worms(Tasnin et al.,2021;Toraason et al.,2022;Isola et al.,2024).Multiple factors contribute to reproductive aging,with chromosomal segregation errors among the most important ones.Accurate chromosome segregation requires the completion of chromatin remodeling events during meiotic prophase(Yang et al.,2024).
基金supported by the China Postdoctoral Science Foundation Grant(2023M734294)Jiangsu Provincial Medical Key Discipline Cultivation Unit(JSDW202215)the National Natural Science Foundation of China(No.82001618).
文摘Primary ciliary dyskinesia(PCD)is a clinically rare,genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections,male infertility,tympanitis,and laterality abnormalities.PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia.Here,we identified a novel nonsense mutation,c.466G>T,in cilia-and flagella-associated protein 300(CFAP300)resulting in a stop codon(p.Glu156*)through whole-exome sequencing(WES).The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm(IDA)and outer dynein arm(ODA).Bioinformatic programs predicted that the mutation is deleterious.Successful pregnancy was achieved through intracytoplasmic sperm injection(ICSI).Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
基金supported by the Yunnan Provincial Key Laboratory of Clinical Virology(No.202002AG070062)the Key Projects of Yunnan Province Science and Technology Department(No.202302AA310044)the National Natural Science Foundation of China(No.82060664).
文摘This study primarily aimed to investigate the prevalence of human papillomavirus(HPV)and other common pathogens of sexually transmitted infections(STIs)in spermatozoa of infertile men and their effects on semen parameters.These pathogens included Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,Pseudomonas aeruginosa,and Staphylococcus aureus.A total of 1951 men of infertile couples were recruited between 23 March 2023,and 17 May 2023,at the Department of Reproductive Medicine of The First People’s Hospital of Yunnan Province(Kunming,China).Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping.Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs.The overall prevalence of HPV infection was 12.4%.The top five prevalent HPV subtypes were types 56,52,43,16,and 53 among those tested positive for HPV.Other common infections with high prevalence rates were Ureaplasma urealyticum(28.3%),Ureaplasma parvum(20.4%),and Enterococcus faecalis(9.5%).The prevalence rates of HPV coinfection with Ureaplasma urealyticum,Ureaplasma parvum,Chlamydia trachomatis,Mycoplasma genitalium,herpes simplex virus 2,Neisseria gonorrhoeae,Enterococcus faecalis,Streptococcus agalactiae,and Staphylococcus aureus were 24.8%,25.4%,10.6%,6.4%,2.4%,7.9%,5.9%,0.9%,and 1.3%,respectively.The semen volume and total sperm count were greatly decreased by HPV infection alone.Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability.Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters,emphasizing the necessity of semen screening for STIs.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
文摘Objective:Ovarian cancer(OC)ranks among the leading causes of mortality among the female cancers worldwide.Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels.However,relatively few studies have explored the impact of post-translational modifications(PTM)on OC progression,which is essential for uncovering new therapeutic targets.This study aimed to systematically identify the key PTM types involved in OCprogression,and to explore and evaluate their translational potential as therapeutic targets.Methods:First,we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females.After identifying lactylation as the PTM with the most significant differences,we selected representative samples for label-free mass spectrometry to identify specific lactylation sites.Next,we transfected A2780(OC)cells with either wild-type(WT)or mutant(K192A[Q])poly(ADP-ribose)polymerase 1(PARP1)conjugated to enhanced green fluorescent protein(EGFP)with a StrepⅡpeptide tag and assessed various cellular indexes related to cell proliferation(clonogenicity assay),migration(scratch wound healing assay),and reactive oxygen species levels.Results:Pan-lactylation was significantly upregulated in clinical OC samples,with PARP1 lactylation at K192 being one of the most common modifications.The growth and migration of A2780 cells were markedly suppressed by overexpressing PARP1-WT but not mutant PARP1.Overexpressing PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2(ERK1/2).Conclusion:This study uncovered a novel PTM of PARP1 in OC,lactylation,and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway.Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.
基金supported by National Natural Science Foundation of China(22374080,22174068,21722504)Primary Research&Development Plan of Jiangsu Province(BK20221303,BE2022796)+1 种基金Open Foundation of State Key Laboratory of Reproductive Medicine(SKLRM-2022BP1,JX116GSP20240507)Science and Technology Development Fund of NJMU(NJMUQY2022003)。
文摘Drug resistance remains a major challenge in breast cancer chemotherapy,yet the metabolic alterations underlying this phenomenon are not fully understood.There is much evidence indicating the cellular heterogeneity among cancer cells,which exhibit varying degrees of metabolic reprogramming and thus may result in differential contributions to drug resistance.A home-built single-cell quantitative mass spectrometry(MS)platform,which integrates micromanipulation and electro-osmotic sampling,was developed to quantitatively profile the tricarboxylic acid(TCA)cycle metabolites at the single-cell level.Using this platform,the metabolic profiles of drug-sensitive MCF-7 breast cancer cells and their drug-resistant derivative MCF-7/ADR cells were compared.This results revealed a selective upregulation of downstream TCA cycle metabolites includingα-ketoglutarate,succinate,fumarate,and malate in drug-resistant cancer cells,while early TCA metabolites remained largely unchanged.Furthermore,notable variations in the abundance of the metabolites were observed in individual cells.The comparative analysis also revealed that not all MCF-7/ADR cells exhibit the same degree of metabolic deviation from the parental line in the metabolites during resistance acquisition.The observed metabolic profiles indicate enhanced glutaminolysis,altered mitochondrial electron transport chain activity,and increased metabolic flexibility in drug-resistant cancer cells that support their survival under chemotherapeutic stress.The findings further suggest the potential for incorporating cellular metabolic heterogeneity into future drug resistance studies.
基金supported by the National Key Research&Developmental Program of China(2022YFC2703800,2022YFC2703000)the National Natural Science Foundation of China(82125014,82371646,32070847)+1 种基金Basic Science Center Program of NSFC(31988101)the Natural Science Foundation of Shandong Province(ZR202105250005,ZR2022YQ69,tsqn202211371).
文摘Premature ovarian insufficiency(POI)is characterized by irreversible loss of ovarian function before 40 years of age and affects 3.7%of women worldwide(Golezar et al.,2019;Huang et al.,2021).Raised serum follicle-stimulating hormone(FSH)levels,menstrual disturbance,and estrogen deficiency are the main symptoms of POl(European Society for Human Reproduction et al.,2016).Besides infertility,patients have an increased risk of long-term complications due to the early deficiency of ovarian steroids,such as osteoporosis,cardiovascular disease,and metabolic disorders(lshizuka,2021).Due to the lack of biomarkers for prediction or early diagnosis,most patients are not diagnosed until the failure stage(serum levels of FSH above 25 IU/L and amenorrhea),missing opportunities for intervention.Therefore,developing sensitive biomarkers for diminished ovarian reserves is paramount for timely treatment to improve reproductive outcomes and prevent long-term complications.
基金supported by the National Natural Science Foundation of China (U22A20277,81971373)Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202215)+1 种基金333 High-level Personnel Training Project of Jiangsu Province (BRA2019109)Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX22_1826)。
文摘Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.
文摘Medically assisted reproduction(MAR)techniques are highly dependent on the sperm quantity and quality.Low sperm concentrations can be bypassed at least to some point by the usage of more sophisticated MAR techniques like intracytoplasmic sperm injection(ICSI).Compared to this,disruptions in established indicators of sperm quality like motility or morphology pose greater challenges for the therapy of couple infertility.
