Journal of Assisted Reproduction and Genetics最新文献

{"title":"Mitochondrial FIS1 level in cumulus cells correlates with morphological grades of human cleavage-stage embryos.","authors":"Yizhen Sima, Sanbao Shi, Zhunyuan Min, Yuning Chen, Yongning Lu, Hongying Sha, Suying Liu","doi":"10.1007/s10815-025-03431-7","DOIUrl":"10.1007/s10815-025-03431-7","url":null,"abstract":"<p><strong>Purpose: </strong>Advanced-age women have a lower good-quality embryo rate (GQER) compared to young women. However, GQER varies widely within the same age group, suggesting that factors beyond age influence embryo quality. Mitochondria regulate cellular metabolism through dynamic fission and fusion alterations. Specifically, cumulus cell (CC) mitochondria regulate not only the metabolism of CCs but also of adjacent oocytes. This study aims to investigate the relationship between CC mitochondrial dynamics and oocyte developmental potential post-fertilization.</p><p><strong>Methods: </strong>CCs were collected from 183 women aged 25-45 undergoing single sperm intracytoplasmic injection-embryo transfer treatments. Samples were stratified by age into young (< 35) and advanced age (≥ 35) groups. Each group was further subdivided into high and low subgroups based on day 3 GQER. Mitochondrial morphology, dynamics, fission-fusion gene expression, and mitochondrial functions were compared among groups and subgroups.</p><p><strong>Results: </strong>Consistent with the literature, data analysis from our laboratory revealed significant variances in GQER among individuals of the same age group. Morphological analysis suggested a negative correlation between GQER and mitochondrial length in CCs (P < 0.0001, r = - 0.38). Live-cell imaging showed that both fission and fusion frequencies of CC mitochondria in the advanced-age group were lower than those in the young group (P = 0.009, P = 0.01). Additionally, within the advanced-age group, CC mitochondria from the low GQER subgroup exhibited lower fission frequency and fission-fusion ratios compared to the high GQER subgroup (P = 0.04, P = 0.01). Consequently, GQER positively correlated with mitochondrial fission-fusion ratio in CCs (P = 0.01, r = 0.44). Notably, there were no significant differences in the expression of mitochondrial fusion-related proteins (OPA1, MFN1, and MFN2) between the advanced-age and young groups or among the subgroups. However, levels of fission proteins, including FIS1 and MFF, were significantly lower in the advanced-age group compared to the young group and in the low GQER subgroup compared to their high GQER counterparts. qPCR results further indicated that fis1 and mff mRNA levels in CCs were positively correlated with GQER (P < 0.0001, r = 0.55; P = 0.0025, r = 0.41). The CCs from the low GQER subgroup exhibit a higher level of mitochondrial dysfunction.</p><p><strong>Conclusions: </strong>Mitochondrial morphology, fission-fusion balance, and fission-fusion gene expression in CCs influence early embryonic development, independent of age. Of these factors, the FIS1 level shows the most robust correlation with GQER.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"2099-2114"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of GnRH agonist trigger on subsequent follicular phase length in ART cycles.","authors":"Roza Berkovitz-Shperling, Yaara Libai, Shir Aviv, Ben-Yosef Dalit, Azem Foad, Feferkorn Ido","doi":"10.1007/s10815-025-03503-8","DOIUrl":"10.1007/s10815-025-03503-8","url":null,"abstract":"<p><strong>Research question: </strong>Does the use of GnRH agonist trigger versus hCG trigger affect the length of the subsequent follicular phase in women?</p><p><strong>Design: </strong>A retrospective cohort study analyzing 196 women undergoing controlled ovarian stimulation with freeze-all for PGT-M at a university-affiliated fertility center; 132 received GnRH agonist trigger, and 64 received hCG trigger.</p><p><strong>Results: </strong>The GnRH agonist group demonstrated a significantly longer subsequent follicular phase compared to the hCG group (18.98 ± 3.54 vs. 16.06 ± 3.13 days, P < .001), with extended follicular phase occurring in 90.2% versus 60.9% of cycles (P < .001). Both groups had comparable antral follicle counts (14.52 ± 7.71 vs. 13.00 ± 15.36, P = .748). Multiple regression analysis identified GnRH agonist trigger as a significant independent predictor of subsequent follicular phase length (coefficient = 4.552, 95% CI: 3.058-6.045, P < .001), along with BMI (coefficient = 0.188, 95% CI: 0.019-0.357, P = .030). The model explained 31.4% of the variance in follicular phase length (F = 7.516, P < .001). After adjusting for confounding variables, pregnancy rates were comparable between groups (OR = 1.763, 95% CI: 0.798-3.505, P = .173).</p><p><strong>Conclusions: </strong>The GnRH agonist trigger prolongs the subsequent follicular phase compared to the hCG trigger without compromising pregnancy rates. BMI showed a statistically significant but modest association with follicular phase length that requires further validation. These findings have important implications for optimizing the timing of frozen embryo transfer in subsequent cycles and may facilitate more personalized monitoring protocols.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1917-1924"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the genetic association between abnormal sperm parameters and depression: a transcriptome-wide analysis of 157 participants.","authors":"Yinwei Chen, Taotao Sun, Penghui Yuan, Chang Liu","doi":"10.1007/s10815-025-03470-0","DOIUrl":"10.1007/s10815-025-03470-0","url":null,"abstract":"<p><strong>Purpose: </strong>Depression often occurs in the males with semen abnormalities. Evidence suggested a genetic correlation between depression and the pathogenesis of abnormal sperm parameters, whereas the mechanisms remained unclear.</p><p><strong>Methods: </strong>Genomic datasets of major depressive disorder (MDD) and abnormal sperm parameters were obtained from the Gene Expression Omnibus database. After screening the datasets, differentially expressed genes (DEGs) were identified. GO and pathway enrichment analyses, a protein-protein interaction network, and receiver operator characteristic curve analysis were conducted. Then, MDD-related DEGs (MDRGs), the external validation, immunological, and translational regulation analysis were performed. Moreover, tissue expression of MDRGs was explored.</p><p><strong>Results: </strong>A total of 249 overlapped MDRGs were discovered in the MDD and abnormal sperm parameters gene sets. MDRGs had a tight relationship with adhesion-associated and PI3 K-Akt-associated biological signaling. The protein-protein interaction module showed the enriched pathways involved in neuron differentiation and cell adhesion. Drug prediction revealed ten pharmacologic candidates. Finally, two hub MDRGs were identified and validated with good diagnostic values. Immunological and translational results showed three closely correlated kinds of CD8 + T lymphocytes, neutrophils, and macrophages, 19 transcription factor-MDRGs, and 71 miRNA-MDRGs interactions. Furthermore, expression signatures of Carnosine Dipeptidase 2 (CNDP2) and Galectin 3 Binding Protein (LGALS3BP) were displayed in cortex and testis.</p><p><strong>Conclusion: </strong>Our study discovered the genetic profiles in abnormal sperm parameters and MDD and elucidated enriched pathways and molecular associations between hub genes and immune infiltration. These findings provide novel insights into the common pathogenesis of both diseases as well as the potential biomarkers for MDD-associated abnormal sperm parameters.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"2003-2017"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosomal segregation and recombination in human sperm cells from reciprocal translocation carriers.","authors":"Yi Yang, Ming Yang, Minjie Shao, Nan Wang, Yifang Yan, Xiaohui Zhu, Liying Yan, Jie Qiao, Zhiqiang Yan","doi":"10.1007/s10815-025-03492-8","DOIUrl":"10.1007/s10815-025-03492-8","url":null,"abstract":"<p><strong>Purpose: </strong>To determine whether recombination occurring around the breakpoints of translocated chromosomes may affect the accuracy of the current linkage analysis-based diagnosis of reciprocal translocation (RT) embryos.</p><p><strong>Methods: </strong>Here, we have selected 688 single sperm cells sampled from 14 RT carriers with signed informed consent before semen collection and systematically investigated their chromosomal segregation patterns and potential recombination of translocated chromosomes.</p><p><strong>Results: </strong>We found that 39.96% of sperm cells showed alternative segregation patterns to produce normal and chromosomally balanced sperm cells, while 39.01% presented with an adjacent-1 segregation pattern, and 16.06% presented with an adjacent-2 segregation pattern, and 4.59% presented with a 3:1 segregation pattern. Moreover, we discovered a previously unknown segregation pattern at 0.38% occurrence. Notably, of the 887 recombination events on RT-associated chromosomes identified, 18 recombination events were located within the range of 5 Mb around breakpoints, among which 10/18 (55.6%) were located within 1-3 Mb of the breakpoint.</p><p><strong>Conclusion: </strong>Our study provides evidence for recombination within the 5 Mb region flanking the breakpoints of translocated chromosomes, and these results suggest a non-negligible risk in the accurate diagnosis of chromosomal translocation in embryos through current linkage analysis-based diagnostic methods.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1949-1959"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological parameters of the blastocyst to predict embryo quality: a systematic review and meta-analysis.","authors":"Lingying Zhang, Chengyu Li, Na Zhu, Emeli Chatterjee, Jie Chen, Tong Liang, Shannan Song, Zulihumaer Yakupu, Mairepati Mahemuti, Baligen Sailikebai, Rongxin Zhu, Xin Zhang, Ji Lei, Guoping Li, Zeyidan Jiapaer","doi":"10.1007/s10815-025-03424-6","DOIUrl":"10.1007/s10815-025-03424-6","url":null,"abstract":"<p><strong>Purpose: </strong>In assisted reproductive technology (ART), the morphological assessment of blastocyst quality is the crucial step that determines the success of embryo transfer. But the relative importance of three blastocyst components-blastocyst expansion (EH), inner cell mass (ICM), and trophectoderm (TE)-for embryos is still a matter of controversy. Therefore, the aim of this meta-analysis is to compare and rank the effects of blastocyst scoring on producing live births.</p><p><strong>Methods: </strong>We systematically searched CINAHL, Cochrane, Embase, MEDLINE, PubMed, Scopus, and the Chinese Medicine database from inception to February 26, 2023. This research includes original articles reporting neonatal outcomes after in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) embryo transfer which contained definitive grading of EH, ICM, and TE characteristics at the blastocyst stage using the Gardner scoring system.</p><p><strong>Results: </strong>We conducted a meta-analysis of 33 studies encompassing 42,974 ART embryos from 46,099 infertile women, with 19 studies reporting live births in 28,918 women involving 30,651 embryos. The analysis revealed that embryo components were ranked by their suitability for live births, with TE (A) scoring highest, followed by ICM (A) and EH (5), while EH was the least favorable. The most favorable embryo morphologies for higher live birth rates were 5AA, 4AA, 6AA, 5AB, 3AA, 5BA, 4AB, 2AA, and 4BA, with 1CC being the least unfavorable.</p><p><strong>Conclusion: </strong>Morphological assessment of embryo quality serves as a crucial protocol in the selection of high-quality embryos after ART, and our study may provide a guideline to assist in the selection of high-quality embryos.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1755-1772"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agouti-signaling protein (ASIP) improves bovine in vitro matured oocyte developmental competence and modulates lipid content.","authors":"Heather L Chaney, Jaelyn Z Current, Mingxiang Zhang, Jianbo Yao","doi":"10.1007/s10815-025-03502-9","DOIUrl":"10.1007/s10815-025-03502-9","url":null,"abstract":"<p><strong>Purpose: </strong>Bovine embryos produced in vitro are developmentally inferior compared to in vivo derived embryos due to the lack of optimization of the oocyte and embryo culture conditions in vitro. Agouti-signaling protein (ASIP), a secreted protein produced by the bovine oocyte, has been recently shown to aid in acquiring oocyte developmental competence. Therefore, in the present study, we aimed to reveal the effects of supplementation of ASIP during in vitro oocyte maturation and embryo culture on subsequent embryonic development.</p><p><strong>Methods: </strong>Cumulus-oocyte complexes or presumptive zygotes were placed in culture medium containing either 0, 1, 10, or 100 ng/mL of recombinant ASIP (rASIP). Effects on development, gene expression, lipid content, and blastocyst cell allocation were examined.</p><p><strong>Results: </strong>Supplementation of rASIP during oocyte maturation was found to significantly increase the blastocyst development rate (P < 0.05) and produced blastocysts with an increased inner cell mass to trophectoderm cell ratio. Addition of rASIP during oocyte maturation increased oocyte (P < 0.05) but not embryo (P > 0.05) lipid levels. The expression of genes involved in lipid metabolism, including FASN, PPAR <math><mi>γ</mi></math> , SCD, CSL1, ELOVL5, and ELOVL6, was not significantly altered in blastocysts due to treatment (P > 0.05). Supplementation of rASIP during embryo culture was not found to affect blastocyst rates.</p><p><strong>Conclusions: </strong>The data presented in this study further support the role of ASIP in oocyte competence and suggest that the supplementation of rASIP during oocyte maturation may lead to the production of blastocyst of increased quality.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1813-1825"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on the perception of pre-semen collection stress and its influencing factors in men on the day of oocyte retrieval in IVF-ET.","authors":"Yuan Jiang, Fengyi Mo, Shuying Wang, Yeqing Huang, Xuzhen Cheng, Lanfeng Xing","doi":"10.1007/s10815-025-03456-y","DOIUrl":"10.1007/s10815-025-03456-y","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the status and influencing factors of perceived stress in men before sperm collection on the day of oocyte retrieval during IVF-ET, thereby providing a theoretical basis for nursing interventions.</p><p><strong>Methods: </strong>A cross-sectional survey was conducted using convenience sampling. We examined 507 male IVF-ET patients undergoing sperm collection using a demographic questionnaire, the Generalized Anxiety Disorder Scale, the Perceived Stress Scale, and the Chinese version of the Connor-Davidson Resilience Scale. Univariate analysis, Pearson correlation, and multivariate linear regression were utilized to identify factors affecting perceived stress before sperm collection.</p><p><strong>Results: </strong>The average score for perceived stress before sperm collection was 14.64 ± 4.54. For generalized anxiety, it was 6.28 ± 3.92; and for psychological resilience, it was 68.14 ± 18.46. Multivariate linear regression analysis revealed that monthly family income, psychological resilience, and anxiety were significant predictors of perceived stress in men before sperm collection (P < 0.05).</p><p><strong>Conclusions: </strong>Men experienced mild anxiety and perceived stress before sperm collection on the day of oocyte retrieval, accompanied by moderate psychological resilience. Monthly family income is independent predictors of perceived stress. Anxiety correlates positively with perceived stress and can predict elevated stress levels, while psychological resilience correlates negatively with stress, serving as a protective factor. Nursing staff must address perceived stress, anxiety, and resilience in men undergoing IVF-ET, providing comprehensive information and support to enhance their psychological well-being.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1875-1883"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examining the fate of frozen embryo inventory: an analysis of patients' embryo disposition decisions.","authors":"Paxton Voigt, Emily Michelle Weidenbaum, Amanda Atkinson, Bailey Knight, Caroline McCaffrey, Jennifer K Blakemore","doi":"10.1007/s10815-025-03460-2","DOIUrl":"10.1007/s10815-025-03460-2","url":null,"abstract":"<p><strong>Purpose: </strong>To determine factors associated with embryo disposition decisions at a large academic fertility center.</p><p><strong>Methods: </strong>We performed a single-center retrospective cohort study of patients who made final embryo disposition (discard or donation to research) between January 1, 2020, and February 28, 2024, via electronic consent. Demographic and cycle-specific variables were collected via chart review. Chi-square and Mann-Whitney U tests were used for data analysis (p < 0.05).</p><p><strong>Results: </strong>Of 1280 patients, 900 (70.3%) discarded embryos and 380 (29.7%) donated to research. Patients who donated were more likely to have a diagnosis of recurrent pregnancy loss (6.1% vs 2.4%, p < 0.002). Patients who chose to donate had transferred more embryos (2 vs 1, p < 0.033) and had transferred more euploid embryos (44.7% vs 36.6%, p < 0.007). There was no difference in total number, number of euploids, or type of embryo disposed (p = 0.24, p = 0.96, p = 0.34). There was no difference observed among those who communicated with the center (p = 0.81) or those using donor gametes (egg p = 0.34, sperm p = 0.29). An additional analysis compared patients who achieved live birth (n = 902) to those who did not (n = 378), and those who donated were more likely to have achieved live birth (32.0% vs 24.1%, p < 0.005).</p><p><strong>Conclusion(s): </strong>At final embryo disposition, more patients discarded embryos than donated. Donators were more likely to have recurrent pregnancy loss as their reason for pursuing embryo creation, transfer more embryos across all cycles, and achieve a live birth. Discarders were more likely to have transferred untested or no embryos.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1845-1852"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing the causative link between CFAP221 variants and asthenoteratozoospermia in humans.","authors":"Gan Shen, Erpo Tian, Chuan Jiang, Yunchuan Tian, Yingteng Zhang, Xiang Wang, Jiang Gu, Ying Shen, Fei Geng","doi":"10.1007/s10815-025-03472-y","DOIUrl":"10.1007/s10815-025-03472-y","url":null,"abstract":"<p><strong>Purpose: </strong>To identify the novel genetic causes of male infertility related to asthenoteratozoospermia in two unrelated Chinese families.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) and sanger sequencing were performed on peripheral blood samples from two infertile patients' families. Papanicolaou stain, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) revealed the morphology and ultrastructure of the infertile patients' spermatozoon. Immunofluorescence staining and single-cell RNA sequencing analysis identified the expression of CFAP221 in the different stages of spermatogenesis sperm cells in mouse and human testes. Bioinformatics analysis predicted the protein interactions involving CFAP221.</p><p><strong>Results: </strong>Pathogenic biallelic variants in CFAP221 were detected in two unrelated infertile men by whole-exome sequencing. Abnormalities in the morphology and ultrastructure of sperm flagella were detected in the two patients. Moreover, during the spermatogenesis, CFAP221 was primarily localized in the flagella of elongating and elongated sperm in humans and mice. Bioinformatics analysis predicted that CFAP221 interacts with flagellum development related proteins such as CFAP74, CFAP194, CFAP246, and CFAP297, and is co-expressed with these proteins in various spermatids during mouse spermatogenesis. Furthermore, intracytoplasmic sperm injection (ICSI) treatment can rescue male infertility caused by harmful variants in CFAP221.</p><p><strong>Conclusion: </strong>Our findings suggested that CFAP221 is a novel causative gene for male infertility and our findings would guide clinical ICSI treatment and diagnosis of male infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"1975-1987"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Mullerian hormone (AMH) protects ovarian follicle loss by downregulating granulosa cell function in in vitro and in vivo models.","authors":"Laura Detti, Michael C Mari, Michael P Diamond, Ghassan M Saed","doi":"10.1007/s10815-025-03473-x","DOIUrl":"10.1007/s10815-025-03473-x","url":null,"abstract":"<p><strong>Purpose: </strong>AMH inhibits hormone production in luteinized granulosa cells (GCs) and stalls ovarian follicle development in vitro and in vivo. We sought to confirm AMH's mechanism of action through SMAD activation and investigate AMH inhibition of follicle development and function, in vitro and in vivo.</p><p><strong>Methods: </strong>A primary culture of GCs isolated from follicular fluid was used, and cells were treated with recombinant AMH (rAMH) or placebo for 24 h. For the mouse model, 18-weeks old C57BL female mice were either euthanized at the beginning or treated with rAMH or normal saline for 3 weeks. Primordial (PDF), primary follicle (PRF), secondary (SEF), and tertiary follicles (TEF) were calculated. Real-time RT-PCR and ELISA were performed to quantify GC gene expression and protein translation of human SMAD 1, 5, and 8, FSH-R and mouse FSH-R, inhibin B, caspase 3, Ki67, BMP15, GDF9, and the epigenetic regulators miRNAa and b.</p><p><strong>Results: </strong>In vitro, rAMH-treated GC showed activation of the SMAD 1, 5 and downregulation of SMAD 8, with greater magnitude at increasing rAMH doses (p < 0.04) and consequential control of downstream regulators. In vivo, the rAMH-treated mice showed increased SEFs and decreased PRFs while PDFs, TEFs, were unchanged compared with baseline. Compared with Placebo, the rAMH group showed increased PDFs, while PRFs, and TEFs were significantly decreased, and SEFs were unchanged.</p><p><strong>Conclusions: </strong>AMH caused SMAD activation in a dose-dependent manner, with downstream downregulation of cell function and replication, also through activation of miRNAs. These mechanisms were confirmed by the in vivo findings with ultimate downregulation of follicular development and preservation of the ovarian follicle number. Counteracting follicular depletion, AMH could be used to protect the ovarian follicle reservoir.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":"2029-2037"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}