Molecular human reproduction最新文献

{"title":"Heparin prevents inflammation-induced pregnancy loss in mice through its anti-inflammatory effects.","authors":"Tomoko Ichikawa, Yasuyuki Negishi, Takami Watanabe, Etsuko Toda, Mika Terasaki, Satoko Nakamura, Mitsuki Murofushi, Shinji Asari, Yuki Kaito, Asako Watanabe, Aya Ono, Toshiyuki Takeshita, Rimpei Morita, Yoshimitsu Kuwabara","doi":"10.1093/molehr/gaag052","DOIUrl":"10.1093/molehr/gaag052","url":null,"abstract":"<p><p>Excessive inflammation at the feto-maternal interface is a major contributor to adverse pregnancy outcomes, including miscarriage and preterm birth. Heparin, which is widely used as an anticoagulant, has also been recognized as possessing anti-inflammatory properties; however, its role in inflammation-driven pregnancy complications remains unclear. In this study, we examined whether unfractionated heparin (UFH) prevents inflammation-induced miscarriage and preterm birth in mice. Lipopolysaccharide (LPS)-induced murine models were used to mimic inflammation-driven pregnancy complications. Pregnant C57BL/6 mice were administered LPS to induce miscarriage or preterm birth, with or without UFH treatment. Immunological, histological, and ex vivo analyses were performed to evaluate inflammatory responses and tissue integrity at the feto-maternal interface. UFH markedly reduced both miscarriage rates and the incidence of preterm birth. It decreased the M1/M2 macrophage ratio and suppressed the production of proinflammatory cytokines, including interleukin-12 (IL-12) and tumor necrosis factor-alpha. UFH also reduced interferon-gamma production by T and natural killer T cells, and downregulated Tbx21 expression in decidual tissues, indicating the attenuation of a proinflammatory immune environment. These protective effects were observed without substantial changes in coagulation parameters. Ex vivo experiments further showed that UFH directly suppressed LPS-induced IL-12 production by decidual macrophages. Collectively, these findings indicate that UFH prevents inflammation-induced miscarriage and preterm birth by modulating immune responses at the feto-maternal interface, independent of its anticoagulant activity.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-coordinated synergism for placental gene regulation throughout pregnancy.","authors":"Caio I S Braga, Gisele Gouveia, Rayssa Feitosa, Caroline Camilo, Veronica Euclydes, Guilherme V Polanczyk, Sérgio N Simões, Suzana de Siqueira Santos, David C Martins, Helena Brentani","doi":"10.1093/molehr/gaag043","DOIUrl":"10.1093/molehr/gaag043","url":null,"abstract":"<p><p>The regulation of gene expression by microRNAs (miRNAs) is essential during development. However, it is necessary to move beyond individual miRNAs to understand their functions and the intricate interplay as a coordinated system. To address this, we developed and implemented a network approach named miRNA-gene synergic co-regulatory networks. This method builds networks identifying pairs of genes jointly regulated (co-regulation) by multiple miRNAs (synergism). Using these networks, focusing on placental genes, we evaluated the coordinated regulation of miRNAs from different origins (maternal circulating extracellular vesicles (EVs) or placental tissue) and at different times (increased expression in the first or third trimester of pregnancy) using both public and original data. We observed that synergic co-regulatory networks displayed properties compatible with scale-free topology. When comparing the co-regulation networks produced by miRNAs differentially expressed at distinct gestational periods, we identified that miRNAs from the maternal circulation were more coordinated at the first trimester, while the miRNAs from the placental tissue were more coordinated at the third trimester. Regarding maternal circulating miRNAs in the first trimester, we identified a co-expression module that was negatively associated with birth weight. This module, together with other miRNAs expressed at higher levels in the first trimester, regulates transforming growth factor beta (TGF-β) signaling pathways that are important for uteroplacental circulatory development. Overall, the results of this study reinforce the idea that miRNAs, whether associated with EVs in maternal circulation or derived from placental tissue, constitute a regulatory system with dynamic coordination throughout pregnancy.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of male neogametogenesis in a three-dimensional microenvironment supporting successful fertilization and proper embryo development.","authors":"Eros Lari, Lily Ng, Philip Xie, Stephanie Cheung, Sabrina Bains, Zev Rosenwaks, Gianpiero D Palermo","doi":"10.1093/molehr/gaag036","DOIUrl":"10.1093/molehr/gaag036","url":null,"abstract":"<p><p>In regenerative medicine, several attempts have been made to produce functional de novo gametes from mouse embryonic stem cells by utilizing three-dimensional (3D) culture systems. We attempted to perform neogametogensis in a novel 3D niche to generate neo-gametes ready to be used for insemination. Mouse embryonic stem cells were initially cultured on a gelatin-coated 6-well plate with a monolayer of fibroblasts before being encapsulated in sodium alginate spheres. These spheres were then immersed in specially formulated epiblast-like cell followed by primordial germ cell-like cell medium to promote differentiation into germ-like cells. Over the course of differentiation, immunofluorescence analysis revealed consistent expression patterns of spermatogenic markers. Cells were assessed for DAZL (early germ cell marker) VASA (spermatocyte), BOULE (post-meiotic) and acrosin (spermatid). The differentiated cells were then injected into oocytes and activated by calcium ionophore. Embryo development was monitored via time-lapse microscopy. Spherified neogametes on D(day)22, 29, and 36 achieved fertilization rates of 61.1%, 82.7%, and 80.0%, respectively, and blastulation rates of 20.5%, 36.0%, 26.3%, respectively. Controls exhibited fertilization rates of 89.1% and blastulation rates of 76.3%. When embryo morphokinetics were considered, D29 embryos reached compaction at 64 h and blastulation at 77 h, mirroring closely the control's timing of 63 and 77 h, respectively. D22 embryos displayed the most delayed embryo development, of which compaction occurred at 68 h and blastulation at 106 h. Despite normal fertilization and successful blastulation, the efficiency rate remained below optimal levels. Nevertheless, our system could produce viable offspring, demonstrating that replicating the 3D seminiferous tubule environment is crucial for generating artificial gametes. This eliminates the need for allogenic/xenogenic transplantation in experimental animals.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13338338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148163559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-molecule ovastacin inhibitors preserve fertilization competence of murine eggs by mimicking fetuin-B function.","authors":"Nele von Wiegen, Larissa Schömbs, Aleksander Moldt Haack, Yufeng Pan, Kathrin Tan, Carlo Schmitz, Willi Jahnen-Dechent, Albrecht Martin Clement, Julia Floehr, Christian Behl, Stefan Tasler, Claudia Tredup, David Baska, Daniel Ramsbeck, Hagen Körschgen","doi":"10.1093/molehr/gaag041","DOIUrl":"10.1093/molehr/gaag041","url":null,"abstract":"<p><p>Infertility represents a major global health challenge and has driven increasing reliance on ART. However, fertilization success in vitro is often limited when physiological egg-sperm interaction is preserved, largely due to premature hardening of the zona pellucida (ZP), the extracellular matrix surrounding the oocyte that controls sperm access. ZP hardening is physiologically triggered after fertilization by ovastacin-mediated cleavage of ZP protein 2 (ZP2) to protect the early embryo. However, if not inhibited prematurely, this cleavage reduces egg competence. In vivo, ovastacin is restrained by the plasma protein fetuin-B, largely absent in IVF media. Whether this process can be pharmacologically targeted has yet to be explored. Here, we identify and functionally characterize small-molecule hydroxamate inhibitors that transiently inhibit ovastacin in murine oocytes and evaluate their ability to control fertilization competence. A lead compound preserved ZP2 integrity and fertilization rates at 86% (±1%) after 8 h of in vitro culture, compared to 57% (±7%) in controls. Importantly, inhibitor-treated embryos developed to the blastocyst stage without abnormalities. These findings establish transient ovastacin inhibition as simple, non-invasive pharmacological strategy to ensure IVF outcomes while preserving physiological egg-sperm interaction mechanisms.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proceedings of the first European Ovary Workshop (EOW 2025), Lagos, Portugal, 17-20 February 2025.","authors":"Christiani A Amorim, Susana M Chuva de Sousa Lopes, Michael Klutstein, Miguel Angel Brieño-Enriquez, Richard A Anderson, Francesca E Duncan, Michel De Vos, Pauliina Damdimopoulou, Pierre Comizzoli, Suzannah A Williams, Yvonne O'Meara, Hajra Khattak, Seppe Segers, Jennifer R Gruhn, Ignasi Roig, Stine Gry Kristensen","doi":"10.1093/molehr/gaag039","DOIUrl":"10.1093/molehr/gaag039","url":null,"abstract":"<p><p>The inaugural European Ovary Workshop (EOW 2025), that was held on 17-20 February 2025, in Lagos, Portugal, brought together 165 scientists, clinicians, and early career researchers from 28 countries to advance ovarian biology from fundamental mechanisms to clinical translation. The program featured 12 scientific sessions, 17 keynote lectures, 15 selected short talks, 89 flash talks, and >90 posters spanning meiosis, folliculogenesis, ovarian reserve, aging, microenvironment, bioengineering, fertility preservation, environmental toxicology, wildlife conservation, patient-public involvement in science, and ethics. A comprehensive networking program combined formal and informal activities to stimulate scientific exchange and interaction across disciplines and career stages. Post-workshop feedback (n = 86) reflected high satisfaction with scientific content (rated 4.6/5), speaker quality (4.7/5), and networking (4.4/5), while identifying opportunities to expand clinical topics, diversify model organisms, and improve poster logistics. EOW 2025 established a unique community and a biennial platform to accelerate discovery and translation in ovarian research.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological basis of contraceptive function of a GSK3α-selective inhibitor, manifested during epididymal sperm maturation.","authors":"Aditi Khamamkar, Rounak Roy, Dhanu Anneyplar Shivakumar, Neha Choudhari, Rahul Dutta, Michel Weïwer, Satish Kumar Adiga, Srinivasan Vijayaraghavan, Souvik Dey","doi":"10.1093/molehr/gaag049","DOIUrl":"10.1093/molehr/gaag049","url":null,"abstract":"<p><p>Glycogen synthase kinase 3 alpha (GSK3α) has emerged as a prospective target to develop male contraceptives. Global or testis-specific loss of GSK3α, but not GSK3β, results in male infertility. Previous studies demonstrated that the GSK3α-selective inhibitor BRD0705 induces reversible infertility in heterozygous mice. Here, we show that BRD0705 induces similar infertility in wild-type male mice. Fertility outcomes remain largely unaltered following superovulation in female mice mated with BRD0705-treated males. Further, no evidence of foetal resorption was observed in these females. Sperm count in treated mice was not altered; however, morphological defects appeared during their passage through the epididymis. The GSK3α inhibitor affected pathways related to the enzyme's catalytic activity in epididymal sperm. Phosphoproteomic analysis of sperm from inhibitor-treated mice showed that phosphorylation of over 50 proteins involved in motility, metabolism, and fertility, among others, was significantly altered. Among the highly hypophosphorylated proteins, four are likely substrates of GSK3 (viz., AKAP4, NT5C1B, SPATA18, and TRA2B). Analysis of the seminiferous tubules of BRD0705-treated mice showed normal spermatogenesis, suggesting that the drug did not affect developing spermatogenic cells. However, in vitro exposure of post-meiotic germ cells demonstrated their susceptibility to this inhibitor. BRD0705, therefore, shows only a non-genomic effect at the post-translational level. These findings support GSK3α inhibition via BRD0705 as a non-hormonal, on-demand, and reversible male contraceptive strategy.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epididymosomes: a key to sperm maturation and infertility therapeutics.","authors":"Yu-Xin Wei, Shu-Ying Guan, Tao Yu, Zhao-Jin Luan","doi":"10.1093/molehr/gaag048","DOIUrl":"10.1093/molehr/gaag048","url":null,"abstract":"<p><p>Epididymosomes as key communication mediators for maintaining organismal homeostasis and coordinating life activities, play a crucial role in the reproductive system. Epididymosomes directly drive sperm to complete functional maturation in the epididymis by delivering bioactive molecules such as proteins, nucleic acids, and lipids, endowing them with motility and fertilization potential. Yet, deviations in epididymosome quantity, compositional profiles, or functional capacities may impede sperm maturation and culminate in fertilization failure, thereby establishing them as key etiological contributors to male infertility. This review comprehensively synthesizes the core roles of epididymosomes in sperm functional maturation, detailing their mechanisms of biogenesis, molecular makeup, and the molecular networks and signaling pathways that govern sperm maturation. It also focuses on exploring the prospects for clinical application of epididymosomes in treating male infertility, alongside the current limitations that need to be addressed. We put forward the development of novel diagnostic markers and targeted therapeutic strategies, drawing on how epididymosome contents regulate sperm functional maturation, and offer actionable suggestions for future research.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PRRC2A deficiency disrupts m6A-dependent RNA processing and meiosis in human spermatogenesis.","authors":"Hui Yu, Na Zhang, Xueping Liu, Hao Geng, Kuokuo Li, Dongdong Tang, Mingrong Lv, Yunxia Cao","doi":"10.1093/molehr/gaag042","DOIUrl":"10.1093/molehr/gaag042","url":null,"abstract":"<p><p>The formation of N6-methyladenosine (m6A) is the most prevalent internal RNA modification in eukaryotic transcripts and plays an essential role in spermatogenesis. PRRC2A is an m6A reader that is indispensable for meiotic progression and is essential for maintaining spermatocyte identity during mouse spermatogenesis. However, its contribution to human spermatogenesis remains unknown. In this study, we investigated a man diagnosed with non-obstructive azoospermia (NOA) and two with severe oligozoospermia, all carrying biallelic PRRC2A variants. All patients exhibited impaired spermatogenesis. The patient with NOA showed marked arrest at meiotic metaphase I or delayed entry into metaphase. RNA-seq and m6A-seq data demonstrated that his PRRC2A deficiency was accompanied by altered chromatoid body-associated RNA regulatory architecture and affected histone-to-transition protein exchange during spermiogenesis. Despite the presence of PRM2-positive spermatids, testicular spermatozoa retrieved from the NOA patient failed to achieve fertilization via TESE-ICSI, possibly due to impaired DNA integrity arising from a perturbed histone-to-protamine transition. In the remaining cases, repeated ART attempts resulted in fertilization failure or early embryonic arrest. A successful pregnancy was ultimately achieved only through donor sperm IVF-ET. The concordance between molecular defects and consistently poor fertilization outcomes across independent individuals supports a pathogenic role for PRRC2A deficiency. We suggest that the disruption of an m6A reader compromises meiotic progression, as well as sperm functional competence and fertilization capacity, although the limited sample size precludes formal statistical inference. By linking epitranscriptomic dysregulation to adverse ART outcomes, this study expands the molecular basis of severe male factor infertility and has direct implications for genetic diagnosis, prognosis of fertilization potential, and reproductive counselling.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D receptor in intrauterine adhesion: a hypothesis-driven review of potential roles and mechanistic insights.","authors":"Min Yong, Xianghong Pu","doi":"10.1093/molehr/gaag046","DOIUrl":"10.1093/molehr/gaag046","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) is a fibrotic disorder of the endometrium associated with menstrual disturbance, infertility, recurrent pregnancy loss, and adverse obstetric outcomes. Although surgical adhesiolysis remains the main treatment, recurrence is common, highlighting the need for better understanding of molecular mechanisms underlying endometrial fibrosis and repair. Vitamin D receptor (VDR), a nuclear hormone receptor involved in cell differentiation, immune regulation, autophagy, and tissue remodeling, has recently been implicated in IUA pathogenesis. This review summarizes current evidence on VDR expression and function in IUA, with emphasis on its potential regulation of autophagy, epithelial-mesenchymal transition (EMT), and pro-fibrotic mTOR, AKT, and MAPK/ERK signaling. Available data suggest that reduced VDR expression in endometrial tissue is associated with increased fibrosis, impaired autophagic flux, p62 accumulation, and EMT activation. However, direct evidence in human IUA and endometrial-specific models remains limited, and much of the mechanistic framework is extrapolated from other fibrotic disease models including kidney, liver, and cancer fibrosis. Therefore, VDR should currently be viewed as a biologically plausible regulator and candidate biomarker rather than an established therapeutic target in IUA. We also discuss the potential, but still unproven, role of vitamin D supplementation, VDR agonists and autophagy modulators, as adjunctive strategies. Future studies should validate VDR expression in larger IUA cohorts, develop clinically relevant endometrial models, and test whether VDR-targeted interventions can improve endometrial repair or reduce adhesion recurrence.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated lipidomics and transcriptomics reveal the key role of ceramides in the development of endometriosis.","authors":"Shanshan Mei, Nan Ding, Mengyi Cheng, Chen Zhang, Jinli Miao, Mengli Liu, Xiaojun Shi, Xinyan Wang","doi":"10.1093/molehr/gaag047","DOIUrl":"10.1093/molehr/gaag047","url":null,"abstract":"<p><p>Endometriosis (EMs) is a chronic gynecological disease with poorly understood pathogenesis. This study integrated lipidomics and transcriptomics to systematically investigate aberrant sphingolipid metabolism in EMs, aiming to identify pathogenic mechanisms and therapeutic targets. Differential metabolites and genes in EMs lesions were identified through multi-omics profiling, followed by gene-metabolite network construction via MetaboAnalyst. EMs mouse models were established by intraperitoneal endometrial transplantation. Mice received ceramide (Cer) or EMs therapeutics for 2 weeks. Lesion size, cytokines, Cer levels, apoptosis, SMPD3 expression, and CD206+ macrophage infiltration were assessed using ELISA, TUNEL, western blot, RT‑qPCR, flow cytometry, and dual immunofluorescence. Integrated analysis revealed substantial metabolic and transcriptional alterations in EMs lesions. Sphingomyelin (SM) emerged as a central network hub, while Cer, generated via SMPD3-mediated SM hydrolysis, was markedly accumulated in lesions. In vivo, exogenous Cer(d18:1/20:0) supplementation exacerbated Cer accumulation, enhanced anti-apoptotic capacity, intensified inflammatory responses, and promoted CD206+ macrophage infiltration. Conversely, effective EMs therapeutics suppressed Cer accumulation, downregulated macrophage SMPD3 expression, and reduced CD206+ macrophage infiltration. Collectively, we identify the SM-SMPD3-Cer axis as a novel metabolic driver of EMs progression. Pathological Cer accumulation facilitates lesion development by promoting inflammation, enhancing CD206+ macrophage polarization, and suppressing apoptosis. These findings provide new metabolic insights and a theoretical foundation for Cer-targeted therapeutic strategies in endometriosis.</p>","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}