Biology of Reproduction最新文献

{"title":"The impact of follicle-stimulating hormone receptor mutations on female ovarian function and pregnancy outcomes: a systematic review†.","authors":"Zhan Qu, Bei Yang, Yaping Miao, Bei Wang, Han Shi, Chenchen Cui, Cuilian Zhang, Hua Zhao","doi":"10.1093/biolre/ioaf283","DOIUrl":"10.1093/biolre/ioaf283","url":null,"abstract":"<p><p>As a member of the G protein-coupled receptor (GPCR) family, the follicle-stimulating hormone receptor (FSHR) plays a central role in the regulation of female reproduction. By specifically binding to follicle-stimulating hormone (FSH), FSHR regulates the proliferation and differentiation of granulosa cells, follicular development and estradiol (E2) synthesis. In this article, we summarized 37 clinically relevant mutations of the FSHR gene. These mutations are classified according to their functional impacts as follows: (1) Inactivating mutations are primarily located in the extracellular domain (ECD; e.g., p.Ala189Val) and the transmembrane domain (TMD; e.g., p.Asp224Val). These mutations cause receptor expression defects or signaling impairment, clinically manifesting as resistant ovary syndrome (ROS), premature ovarian failure (POF), or related disorders. These conditions are typically characterized by a preserved primordial follicle reserve but an arrested antral follicle development; (2) Activating mutations are concentrated in the TMD (e.g., p.Asp567Gly) and intracellular loops (ICLs; e.g., p.Val514Ala). They exhibit relaxed ligand specificity and result in ligand-independent constitutive activation. This leads to pregnancy-associated spontaneous ovarian hyperstimulation syndrome (sOHSS), characterized by enlarged ovaries containing multiple follicles and supraphysiologically elevated E2 levels. The review highlights the clinical utility of in vitro maturation (IVM) technology in assisted reproduction for patients with FSHR mutations. Clinical evidence demonstrates that mature oocytes are successfully obtained by circumventing FSH stimulation. Through a \"molecular pathology → mutation classification → clinical phenotypes → therapeutic strategies\" framework, this review establishes a theoretical foundation for precise classification and individualized management of FSHR mutation-related reproductive disorders.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"722-743"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of oxygen concentration and glycosphingolipid effects on spermatogenesis in mouse testicular culture†.","authors":"Shino Nagata, Yu Ishikawa-Yamauchi, Kumiko Katagiri, Takuya Sato, Masahito Ikawa, Takehiko Ogawa","doi":"10.1093/biolre/ioaf284","DOIUrl":"10.1093/biolre/ioaf284","url":null,"abstract":"<p><p>Our previous research highlighted the importance of hormones, free fatty acids, lysophospholipids, and antioxidants in supporting in vitro spermatogenesis in mice through the development of a chemically defined medium (CDM). While it was possible to induce round spermatids through the culture of testicular tissue in medium containing these factors, challenges remained with the low efficiency of spermatogenesis and the differentiation into elongating spermatids. This study aimed to further improve the in vitro spermatogenesis system by exploring optimal oxygen concentrations and identifying additional factors necessary for spermiogenesis. In addition to the conventional oxygen concentration of 20%, three hypoxic environments (15%, 10%, and 7%) were tested, and an oxygen concentration of 10% was found to be optimal for the maintenance and differentiation of germ cells in vitro. To address the limited tissue growth observed under low oxygen conditions, we further supplemented the culture medium with glucose and insulin, which led to a significant increase in tissue size. However, this enhancement in growth did not translate into improved spermatogenic differentiation. Following this, we explored factors involved in the induction of elongating spermatids. The addition of glycosphingolipids to the culture medium modestly promoted the formation of elongating spermatids, suggesting a potential role of glycosphingolipids in haploid cell differentiation. This study offers new insights into the environmental conditions and factors that influence spermatogenesis in mice.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1079-1090"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic profiling identifies fertility markers in bull sperm†.","authors":"Quinn A Hoorn, David A Kenny, Sean Fair, Patrick Lonergan, Constantine A Simintiras","doi":"10.1093/biolre/ioaf234","DOIUrl":"10.1093/biolre/ioaf234","url":null,"abstract":"<p><p>Early and accurate assessment of bull fertility is critical for the success of artificial insemination (AI) programs in cattle production. However, current selection tools, including genomic predictions and standard semen evaluations, offer limited reliability in forecasting field fertility outcomes. To address this limitation, we explored the sperm metabolome as a potential source of novel fertility-associated biomarkers. Using high-throughput untargeted metabolomics, we profiled frozen-thawed sperm from Holstein-Friesian bulls with high (n = 12) and low (n = 12) adjusted fertility scores, each with a minimum of 500 AI service records (range from 519 to 99,953 per bull). Raw peak intensities for 615 metabolites were normalized to the total protein concentration of each sample, and, following data filtration, 547 metabolites were retained for downstream analyses. Unpaired t-tests combined with fold-change thresholding identified 18 differentially abundant metabolites between high fertility and low fertility groups (P < 0.1, absolute fold change >1.5), with significant enrichment in pathways relating to lipid and energy metabolism. Further interrogation of these differentially abundant metabolites in the literature revealed possible metabolic differences associated with calcium channel inhibition and reactive oxygen species production in the low fertility bulls. Machine learning-based biomarker discovery further identified a subset of five metabolites-3-phosphoglycerate, phenylalanine, ceramide, citrate, and citrulline-capable of distinguishing fertility status with high predictive accuracy (AUROC = 0.877; P = 0.02). Overall, these data support sperm metabolomics as a promising omics-based approach to enhance bull fertility evaluation and improve selection strategies in AI programs.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"883-892"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal high-fat diet consumption by male rat offspring of obese mothers accentuates negative outcomes of reproductive function in young adults†.","authors":"Guadalupe L Rodríguez-González, Dayana Méndez-Sánchez, Mayel Chirinos, Luis A Reyes-Castro, Carlos A Ibáñez, Consuelo Lomas-Soria, Gabriela Hernández-Silva, Sergio De Los Santos, Patricia Canto, Elena Zambrano","doi":"10.1093/biolre/ioaf261","DOIUrl":"10.1093/biolre/ioaf261","url":null,"abstract":"<p><p>Maternal obesity (MO) predisposes male offspring to impaired fertility and premature aging of reproductive function. We hypothesized that postnatal high-fat diet (HF) from early childhood to adulthood (second hit) exacerbates MO programmed outcomes in male offspring reproductive capacity. Female Wistar rats ate chow (5%-fat (C)) or HF diet (25%-fat (MO)) from weaning through pregnancy and lactation. Male offspring were weaned on chow (C/C and MO/C) or HF diet (C/HF and MO/HF) and euthanized at postnatal-day 110. Scrotal temperature and epididymal fat were higher in C/HF and MO/HF. Testicles: malondialdehyde (MDA) concentrations were increased in MO/HF, reactive oxygen species (ROS) rose in MO/C and MO/HF, superoxide dismutase (SOD) activity increased in C/HF and MO/HF, and glutathione peroxidase (GPx) activity was higher in C/HF, MO/C, and MO/HF. Testicular mRNA expression of Nrf2, SOD-1, GPx-4, and Bax/Bcl2 ratio was lower in MO/HF. Sperm: MDA concentrations increased in MO/HF, ROS concentrations were elevated in MO/C and exacerbated in C/HF and MO/HF, SOD activity decreased in MO/HF. Sperm motility decreased, while sperm abnormalities increased in C/HF, MO/C, and MO/HF. DNA fragmentation: yellow-stained sperms (low-fragmentation) were increased in MO/C and exacerbated in C/HF and MO/HF; C/HF, MO/C, and MO/HF showed more orange-stained sperms (medium-fragmentation), but MO/HF had the highest increase. MO/HF exhibited an increase in red-stained sperms (high-fragmentation). MO/HF had a decreased fertility rate. MO combined with postnatal environmental factors, has a negative impact on offspring health and leads to greater reproductive alterations in comparison with unhealthy postnatal dietary habits or the programming caused by MO.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1101-1114"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cetrorelix suppresses the dominant follicle and synchronizes follicular waves and ovulation in cattle†.","authors":"Dylan R Farmer, Carlos E P Leonardi, Gregg P Adams, Jennifer Campbell, John L O Oliveira, Jaswant Singh","doi":"10.1093/biolre/ioaf276","DOIUrl":"10.1093/biolre/ioaf276","url":null,"abstract":"<p><p>To determine the effects of a GnRH antagonist on ovarian function in cattle, we tested the hypotheses that cetrorelix will (1) cause regression of the extant dominant follicle by altering gonadotrophin secretion and (2) induce a new follicular wave emergence at a consistent time after treatment. In Experiment 1, heifers were given 1.5 mg cetrorelix im on Days 1-2 (Day 0 = wave emergence), Days 3-4, and Days 6-7, or normal saline (Control, n = 8 per group). The dominant follicle was smaller and regressed earlier in groups treated with cetrorelix on Days 1-2 or Days 3-4 than in Controls (P = 0.01). Plasma LH concentrations were lower (P = 0.04) for 3 days after treatment, and the pre-wave surge in FSH occurred earlier in groups treated with cetrorelix on Days 1-2 or Days 3-4 than Controls (P = 0.01). Corpus luteum diameter was smaller (P = 0.01) in the cetrorelix groups, but luteal vascularity, life-span, or progesterone production was not affected. In Experiment 2, heifers were treated with a single 3 mg dose of cetrorelix on Day 1, 3, or 6, or normal saline (Control, n = 8 per group), given prostaglandin F2a and inseminated. Wave emergence occurred synchronously 3.6 ± 0.3 days after cetrorelix treatment, ovulations occurred 12.4 ± 0.3 days later, and 13/23 heifers became pregnant. In Experiment 3, cetrorelix given at random days of the cycle induced a new wave 3.4 ± 0.3 days later and wave emergence was more synchronous than in saline-treated cows (Barlett test P = 0.04). Results supported hypotheses and provide rationale for the development of new cetrorelix-based protocols for breeding management in cattle.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"966-980"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13017487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable contraceptives differentially affect the hypothalamic-pituitary-gonadal axis and amenorrhea incidence†.","authors":"Alexis J Bick, Chanel Avenant, Carole-Keza Capitaine, Sharoné van Eck, Mu-Tien Lee, Johnson M Moliki, Sigcinile Dlamini, David W Erikson, Jenni Smit, Mags Beksinska, G Justus Hofmeyr, Donita J Africander, Pai-Lien Chen, Janet P Hapgood","doi":"10.1093/biolre/ioaf292","DOIUrl":"10.1093/biolre/ioaf292","url":null,"abstract":"<p><p>Hormonal contraceptives modulate the hypothalamic-pituitary-ovarian (HPO) axis; however, underlying mechanisms and differences between contraceptives are underexplored. The Women's Health Injectable Contraception and HIV trial randomised 521 women to intramuscular depot medroxyprogesterone acetate (DMPA-IM) or norethisterone enanthate (NET-EN) and showed similar decreased estradiol levels, but more amenorrhea for DMPA-IM users. This secondary study excluded for misreporting contraceptive use for 128 participants (DMPA-IM n = 65; NET-EN n = 63). Peripheral blood serum collected at initiation and one week after the 24-week injection (25 W), at peak progestin levels, was analysed for gonadal steroids, progestins and peptide hormones. While no changes were detected in peripheral gonadotropin-releasing hormone levels, DMPA-IM decreased luteinising hormone (LH) less than NET-EN. DMPA-IM increased, while NET-EN decreased follicle-stimulating hormone (FSH). Both contraceptives substantially decreased gonadal steroid levels, more so in NET-EN users for testosterone and estradiol. Post-menopausal-like hypoestrogenic effects were greater than previously reported, consistent with the substantial reduction in LH levels. Whether reduced LH levels are due to direct pituitary, hypothalamic, or supra-hypothalamic effects by progestins, is unclear. MPA, unlike NET, increased fsh expression in LβT2 cells, likely via the glucocorticoid receptor, consistent with direct effects on the pituitary by MPA in women. Amenorrhea associated in a time-varying manner with MPA and HPO hormone levels and LH/FSH, for DMPA-IM but not NET-EN users. HPO hormone profiles differ between DMPA-IM and NET-EN users and compared to pre- and post-menopausal women. Mechanisms affecting amenorrhea likely differ between contraceptives, with lower 25 W LH/FSH being consistent with more amenorrhea for DMPA-IM.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"933-951"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfibrillar-associated protein 5 promotes TGF-β1-induced endometrial epithelial fibrosis in intrauterine adhesion†.","authors":"Jinjin Yang, Li Ren, Xiaoli Gu, Lu Wang, Jinquan Cui","doi":"10.1093/biolre/ioaf242","DOIUrl":"10.1093/biolre/ioaf242","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) is an adhesion of the uterine cavity or cervical canal resulting from damage to the basal layer of the endometrium， usually accompanied by fibrosis of the endometrium. This study analyzed endometrial samples from three IUA patients and three healthy control participants and screened for differentially expressed genes (DEGs) using RNA-seq and bioinformatics techniques. A total of 2402 DEGs were identified in endometrial tissues compared to normal endometrial tissues, among which microfibrillar-associated protein 5 (MFAP5) was upregulated in IUA tissues (log2FoldChange = 3.81, P = 1.98E-08). Meanwhile, clinical tissue specimens revealed remarkably up-regulated MFAP5 expression in endometrial tissues of IUA patients, accompanied by increases in the fibrosis markers collagen type I A 1 and α-smooth muscle actin. A mouse model of IUA was constructed by mechanical curettage. Histopathology revealed that MFAP5 downregulation attenuated IUA model-induced reduction in endometrial gland number and collagen deposition. Furthermore, MFAP5 knockdown alleviated the increase in embryo uptake ratio and the decrease in embryo and placental weight in IUA model. In vitro, the expression of fibrosis indicators was upregulated in Ishikawa cells treated with 5 ng/mL transforming growth factor-β1 (TGF-β1), while MFAP5 siRNA reduced levels of the endometrial fibrosis markers. RNA-seq analysis was performed on normal-treated and MFAP5 knockdown-treated TGF-β1-induced cell lines. Enrichment analysis revealed that the MFAP5 siRNA may be involved in microfibril formation, collagen deposition, and the TGF-β pathway. These results further confirm the potential role of MFAP5 in promoting endometrial fibrosis, which provides new insight for the clinical treatment of IUA.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"871-882"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 as a trigger for inflammatory storms: a potential biomarker for adverse pregnancy outcomes†.","authors":"Fangbin Huang, Jingyi Wu, Qingliang Zheng","doi":"10.1093/biolre/ioaf243","DOIUrl":"10.1093/biolre/ioaf243","url":null,"abstract":"<p><p>The maternal-fetal interface comprises trophoblast cells, immune cells, decidual cells, and various other cellular components that collectively contribute to the maintenance of 1immune homeostasis through the secretion of specific cytokines and hormones. Inflammation plays a crucial role in successful embryo implantation, pregnancy maintenance, and parturition; however, it also exhibits a dual role in reproduction and pregnancy. Excessive activation of inflammatory processes, conversely, may have detrimental effects on pregnancy outcomes. Research has demonstrated that elevated levels of High Mobility Group Box 1 (HMGB1) in maternal circulation correlate with negative pregnancy outcomes, including unexplained recurrent miscarriage, gestational diabetes, and preeclampsia (PE). Furthermore, HMGB1 functions by activating the NF-κB signaling pathway through its interaction with the receptor for advanced glycation end-products (RAGE) and Toll-like receptors (TLRs), which subsequently enhances the expression of downstream pro-inflammatory cytokines such as IL-18, interleukin-1 beta (IL-1β), and TNF-α, thereby contributing to adverse pregnancy outcomes. Collectively, this evidence positions HMGB1 as a potential biomarker for these negative pregnancy results. This review aims to elucidate the mechanisms by which HMGB1 acts as an inflammatory regulatory factor in various adverse pregnancy outcomes and to investigate the potential therapeutic value of HMGB1 antagonists as candidate agents for the prevention and treatment of preterm birth (PB) and inflammatory damage, thereby providing a theoretical foundation for developing intervention strategies targeting HMGB1.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"687-699"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145386925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal intestinal and placental mitochondrial dysfunction, autophagy, and ferroptosis involving intestinal microbiota by gut microbiota transplantation from sheep to mice†.","authors":"Feiyang He, Gao Liu, Huisi Wu, Mabrouk Elsabagh, Yuming Huang, Jianing Wang, Mengzhi Wang, Hao Zhang","doi":"10.1093/biolre/ioaf253","DOIUrl":"10.1093/biolre/ioaf253","url":null,"abstract":"<p><p>Exposure to testosterone (T) in pregnant ewes resulted in placental dysfunction and fetal growth restriction (FGR). However, the impact of T on gut microbiota and its contribution to exacerbating intestinal and placental pathologies remains uncharacterized. Pregnant sheep received intramuscular injections of 100 mg T propionate or a control vehicle. To examine the gut microbiota' s role in T-induced FGR, gut microbiota transplantation (GMT) was conducted from T-exposed and control ewes into antibiotic-treated pregnant mice. The findings demonstrated that T exposure exacerbated mitochondrial impairment, autophagy, and ferroptosis in placental and intestinal tissues, alongside inducing gut microbial dysbiosis. GMT further revealed that pathological alterations were mechanistically linked to gut microbiota imbalance. The findings demonstrated that gut-placental axis play a central role in mediating T-induced mitochondrial dysfunction, autophagy, and ferroptosis in maternal intestinal and placental tissues. These results underscore novel therapeutic opportunities, which operate via the gut-placental axis to mitigate FGR.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1030-1044"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on RNA m6A methylation modification mediating placental disorders induced by maternal stress†.","authors":"Lingtong Gao, Yinan Han, Yuhong Li, Xin Guan, Lu Gao","doi":"10.1093/biolre/ioaf285","DOIUrl":"10.1093/biolre/ioaf285","url":null,"abstract":"<p><p>Maternal stress caused by the environmental factors varied in intrauterine and extrauterine during pregnancy may significantly affect placental and fetal development, as well as offspring health in adulthood. Epigenetic mechanisms are frequently invoked to elucidate these effects. RNA N6-methyladenosine (m6A) modification, one of the most prevalent and abundant post-transcriptional epigenetic modifications in eukaryotic mRNA, has recently garnered widespread attention in life sciences. RNA m6A modification plays critical roles in RNA splicing, translation, localization, stability, and has been implicated in various biological processes, including embryonic development, sex determination, and disease pathogenesis. In studies of placental developmental abnormalities induced by maternal stress during pregnancy, m6A modification has emerged as a key mechanism. This article initially introduces the impact of RNA m6A methylation modification on placental development, subsequently elaborates on recent advances in understanding how maternal stress induces placental abnormalities via m6A modification, and finally summarizes unresolved key questions in this field. This review aims to propose strategies for preventing and treating placental developmental abnormalities caused by maternal stress.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"700-707"},"PeriodicalIF":3.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}