Biology of Reproduction最新文献

{"title":"Targeting the Wnt signaling network in endometriosis: mechanistic insights and translational opportunities.","authors":"Xiaoye Ye, Fei Lv, Aolin Zheng, Shuchen Yu, Shiyu Xia, Yi Jin, Xinyi Yang, Qihang Zhao, Huanqing Chen, Binyan Chen, Ying Hu, Yongfeng Wu, Jinyi Tong","doi":"10.1093/biolre/ioag071","DOIUrl":"https://doi.org/10.1093/biolre/ioag071","url":null,"abstract":"<p><p>Endometriosis is a chronic gynecological disorder defined by the growth of endometrial-like tissue outside the uterus, driven by estrogen-dependent inflammation and progressive fibrosis. According to available data, remodeling and persistent abnormal activation of the Wnt/β-catenin signaling network constitute one of the main molecular bases underlying its progression. Atypical characteristics of this disease include increased proliferation and anti-apoptotic potential of ectopic endometrial cells, as well as invasive phenotypes and progressive fibrosis. The Wnt/β-catenin pathway contributes to these changes through multiple levels of regulation. The pathway modifies the ligand-receptor spectrum within ectopic lesions at the level of ligand-receptor interactions. Certain canonical or non-canonical branches are more likely to be activated due to imbalanced expression of Wnt ligands and Frizzled receptors. This biased activation promotes β-catenin accumulation and nuclear translocation. In parallel, the pathway is modulated by Wnt antagonists and miRNAs. Additionally, it interacts with estrogen-progesterone imbalance, inflammatory mediators, and the immune microenvironment. The pathological processes of endometriosis are co-shaped by these signals. This review provides an organized overview of the roles of Wnt signaling in endometriosis. First, the upstream regulators of Wnt signaling and its interactions with the microenvironment are summarized. Second, the pathological effects of prolonged activation are explained, emphasizing epithelial-mesenchymal transition, fibrosis, and immune evasion. Third, the therapeutic potential of targeting this pathway is assessed, including small-molecule inhibitors, drug repurposing approaches, and nucleic acid- or epigenetic-based techniques. Finally, we propose a conceptual framework for precision treatment and targeted intervention in endometriosis, aiming to offer clinically relevant reference points.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147855900","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":"Perturbation of potassium homeostasis impairs oocyte maturation.","authors":"A R T Krause, F J Diaz","doi":"10.1093/biolre/ioag097","DOIUrl":"https://doi.org/10.1093/biolre/ioag097","url":null,"abstract":"<p><p>Movement of ions such as calcium and zinc are well known regulators of oocyte maturation and fertilization. The specific contribution of potassium ions is less well understood. We tested whether acute disruption of K+ homeostasis perturbs oocyte maturation. A preliminary screen identified PA-6 (IK1/KIR2.x inhibitor) as a robust inhibitor of oocyte maturation. We compared effects of PA-6 to Valinomycin (K+ ionophore) and tetraethylammonium chloride (TEAC; broad voltage-gated K+ channel blocker). PA-6 and Valinomycin completely prevented germinal vesicle breakdown (GVBD) and polar body extrusion. The nuclear envelope remained intact but with the chromatin stretching across the nucleus (PA-6) or remained semi condensed in the nucleus (Valinomycin). TEAC permitted GVBD but 66% were arrested at MI and both MI and MII spindles were abnormal. Thallium-based flux assays showed higher K+ transport in GV than MII oocytes with PA-6 increasing transport in GV only. Valinomycin reduced transport in MII, but not GV oocytes. TEAC enhanced transport in both stages with delayed onset at GV. PA-6 did not elevate cAMP, while Valinomycin and TEAC modestly increased cAMP. Only PA-6 increased mitochondrial membrane potential, while only Valinomycin increased plasma membrane potential. Both PA-6 and Valinomycin blunted depolarization-induced Zn2+ accumulation. Surprisingly, KCNJ2/4/12 transcripts were detected in cumulus oocyte complexes but not in denuded oocytes. However, KCNJX immunoreactivity was present in oocytes indicating uncertainty about the PA-6 targets in oocytes. Collectively, these data identify K+ flux as a central regulator of oocyte maturation that integrates plasma membrane excitability, organelle function, chromatin remodeling, spindle integrity, and zinc dynamics.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833100","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":"Copper Deficiency Disrupts Placental Development and Lipid Metabolism, Contributing to Fetal Growth Restriction†.","authors":"Yu-Jie Ran, Ya-Qi Wang, Jia-Qi Xu, Li Luo, Jing-Tang, Ying-Lin Dong, En-Xiang Chen, Fang-Fang Li, Ling-Ling Ruan, Li-Juan Fu, You-Long Xie, Yu-Bin Ding","doi":"10.1093/biolre/ioag096","DOIUrl":"https://doi.org/10.1093/biolre/ioag096","url":null,"abstract":"<p><p>To investigate how copper deficiency during pregnancy affects placental structure, metabolism, and trophoblast function, contributing to fetal growth restriction (FGR). Pregnant C57BL/6N mice were treated with ammonium tetrathiomolybdate (ATTM) to induce copper deficiency, with two different dosages (30 and 60 mg·kg-1·d-1) administered daily from gestational day 1 to day 14. On day 15, assessments were made on fetal growth, placental development, and spatial metabolomics. In parallel, trophoblast cells (HTR8/SVneo) were subjected to copper chelation or SLC31A1 knockdown to model copper deficiency in vitro. Cell invasiveness and proliferation were evaluated using appropriate assays, along with the measurement of molecular markers to assess the impact of copper deficiency. Copper deficiency significantly reduced maternal serum copper levels, leading to FGR, as evidenced by shorter crown-rump lengths, lower fetal weights, and altered fetal-to-placental weight ratios. Structural abnormalities in the placental junctional zone, including reduced size and altered morphology, were observed. Metabolomic analysis revealed disrupted lipid metabolism, with alterations in glycerophospholipids and fatty acids, and lipid droplet accumulation. Copper deficiency impaired trophoblast migration and invasion, linked to decreased MMP2 and MMP9 expression in vivo and in vitro. In vitro studies also showed altered lipid metabolism in SLC31A1-knockdown trophoblast cells. Copper deficiency disrupts placental structure and lipid metabolism, impairs trophoblast function, and contributes to FGR, highlighting the critical role of copper in fetal development and maternal health.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833126","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":"Estrogen Receptor Expression in GnRH Neurons: Back to the Future.","authors":"Ji-Eun Oh, Haoyun Li, Mary Bunnell, Ashley Chan, Anastasiia Vasetska, Sungsik Park, Lea Stangenes, PoChing Lin, Kun Wang, CheMyong Ko","doi":"10.1093/biolre/ioag095","DOIUrl":"https://doi.org/10.1093/biolre/ioag095","url":null,"abstract":"<p><p>Estrogen feedback within the hypothalamic-pituitary-gonadal (HPG) axis is mediated primarily by upstream estrogen-sensitive neuronal populations, most notably kisspeptin neurons, which translate circulating sex steroid levels into excitatory or inhibitory input to gonadotropin-releasing hormone (GnRH) neurons, the final neural output controlling pituitary gonadotropin secretion. Despite extensive research, the expression and role of estrogen receptors in GnRH neurons remain poorly understood. To systematically evaluate what can be inferred from transcriptomic data alone, we conducted a comprehensive analysis of open-source single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets encompassing mouse embryogenesis through adulthood, supplemented by cross-species datasets from rat, squirrel, pig, and human hypothalami. In adult mice, Esr1 transcripts were detected in a distinct subset of Gnrh1+ cells more frequently than Esr2 transcripts. Notably, this expression was dynamic, with an increased proportion of Esr1+Gnrh1+ cells emerging during maturation, particularly after puberty. In contrast, Esr2 detection remained minimal across developmental stages. Pseudotime analysis showed Esr1+Gnrh1+ cells at late pseudotime, coinciding with advanced maturation states. Cross-species comparisons further revealed species-specific patterns, with Esr1+Gnrh1+ cells consistently more prevalent than Esr2+Gnrh1+ cells in rodents, while ESR2+GNRH+ cells were slightly more detectable in pigs and humans. These results support a model where estrogen signaling within GnRH neurons is heterogeneous, developmentally regulated, and often mediated indirectly through upstream estrogen-sensitive circuits, such as kisspeptin and nNOS neurons. This study provides a comprehensive, unbiased transcriptomic framework for understanding estrogen receptor expression in GnRH neurons, offering new insights into how estrogen might influence reproductive function through both direct and indirect signaling pathways.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833060","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":"A human CEP120 gene variant impairs meiotic spindle building causing aneuploidy†.","authors":"Marlena Duke, Cecilia S Blengini, Sophia Maddocks, Mansour Aboelenain, Christine Prorock-Rogers, Karen Schindler","doi":"10.1093/biolre/ioag094","DOIUrl":"https://doi.org/10.1093/biolre/ioag094","url":null,"abstract":"<p><p>Infertility is increasing, leading more women to seek assisted reproduction treatments than ever before. One of the main causes of infertility and pregnancy loss is aneuploidy, an incorrect number of chromosomes in the embryo or developing fetus, which hinders normal development. Aneuploidy overwhelmingly arises from the missegregation of chromosomes during the maternal meiotic divisions that produce haploid oocytes (or eggs). Variants of genes involved in spindle building are of primary interest when searching for genetic causes of aneuploidy because the oocyte meiotic spindle is responsible for faithful chromosome segregation. We previously identified a genetic variant in a human centrosome gene, CEP120, as associated with high embryonic aneuploidy. To evaluate the functional significance of this genetic variant, we generated a knock-in mouse model and found that female mice had reduced fertility and increased egg aneuploidy. By assessing microtubule re-establishment after cold temperature exposure and warming after vitrification, we found that oocytes from mice harboring the genetic variant had reduced microtubule nucleation efficiency. Because mouse and human oocytes present differences in spindle building mechanism, we modified mouse oocyte spindle building assembly by pericentrin depletion to better mimic human oocytes and found that aneuploidy levels significantly increase in CEP120 variant eggs. Although PGT-A allows the deselection of aneuploid embryos, the development of biomarkers for predisposition to aneuploidy could be used to identify subfertile patients and model their aneuploid risk. Therefore, our data indicate that patients harboring common genetic variants in CEP120 may require additional counseling when considering egg cryopreservation procedures.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833088","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":"Beware of your \"oocyte specific\" Cre line: somatic cell Cre expression in several Zp3-Cre lines and the Gdf9-iCre transgenic line†.","authors":"Paula Stein, Chihiro Emori, Elizabeth Padilla-Banks, Lenka Radonova, Artiom Gruzdev, Masahito Ikawa, Carmen J Williams","doi":"10.1093/biolre/ioag093","DOIUrl":"https://doi.org/10.1093/biolre/ioag093","url":null,"abstract":"<p><p>Several zona pellucida 3 (Zp3)-Cre driver mouse lines are used to enable conditional loss-of-function studies in oocytes. The Knowles Zp3-Cre line, currently maintained live at the Jackson Laboratory, is the most widely published. We recently found that the transgene expressed in the Knowles line contains a truncated metallothionein (Mt1) sequence that is expressed at high levels in oocytes from transgenic mice. This finding led us to search for an alternative Zp3-Cre line that did not express an exogenous Mt1 transcript. We tested a second transgenic Zp3-Cre line and then created our own transgenic Zp3-Cre line, neither of which was oocyte-specific as documented by crossing to the tdTomato reporter line. Similar testing confirmed the exquisite oocyte specificity of the Knowles Zp3-Cre line. An alternative to Zp3-Cre is to use the Gdf9-iCre line, which is reported to be oocyte-specific and expressed beginning at the primordial follicle stage. This line similarly showed high somatic tissue Cre expression. Reasoning that a knock-in approach would ensure oocyte specificity, we used a CRISPR/Cas9 approach to insert Cre into the endogenous Zp3 locus. However, crosses of this knock-in line with tdTomato females revealed high somatic tissue expression. Both the Zp3-Cre knock-in and Gdf9-iCre alleles, when paternally inherited, induced Cre expression by the blastocyst stage, explaining the broad tissue distribution. We conclude that the Knowles Zp3-Cre transgenic line remains the best model for generating oocyte-specific expression, though investigators should be aware of the spurious Mt1 expression from the transgene.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761113","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":"The synaptonemal complex: structure, function, and clinical implications†.","authors":"Fang Yang, P Jeremy Wang","doi":"10.1093/biolre/ioag092","DOIUrl":"https://doi.org/10.1093/biolre/ioag092","url":null,"abstract":"<p><p>The synaptonemal complex (SC) is a highly ordered proteinaceous structure that assembles between homologous chromosomes during the prophase I of meiosis. Conserved as a tripartite architecture across species, the SC plays a central role in chromosome synapsis, meiotic recombination, and faithful chromosome segregation. This review marks the 70th anniversary of the discovery of the synaptonemal complex by Montrose Moses in 1956. In mammals, the SC is composed of eight core (canonical) structural proteins: SYCP1, SYCP2, SYCP3, SYCE1, SYCE2, SYCE3, SIX6OS1, and TEX12. The archetypal SC consists of two lateral elements (SYCP2 and SYCP3), a central element (SYCE1/2/3, SIX6OS1, and TEX12), and numerous transverse filaments (SYCP1). A shared structural feature of SC components is the presence of coiled-coil domains. Although the tripartite organization of the SC is evolutionarily conserved, its constituent proteins exhibit little to no sequence homology across species. In addition to these core components, a number of proteins, including HORMAD1, HORMAD2, TRIP13, SKP1, CDCA5 (Sororin), UBE2I (UBC9), SYCP2L, HSPA2, PSMA8, and FKBP6, associate with the SC. Beyond serving as a structural scaffold essential for homolog synapsis, SC proteins interact with key recombination factors such as DMC1, RAD51, and TEX11, thereby regulating recombination progression and crossover formation. Genetic, biochemical, and structural analyses of SC components have provided important mechanistic insights into SC assembly and function, as well as their clinical relevance to non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) in humans.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761097","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":"Gonadotrope Remodeling in Sustained Low Estrogen States: Single-Cell Transcriptomic Analysis Reveals Gonadotrope Subtypes and Activation of Stem Cell Populations.","authors":"Angela K Odle, Tiffany K Miles, Ashley K Herdman, Lillian G Clark, Stephanie D Byrum, Alex N Lagasse, Anessa C Haney, Angus M MacNicol, Gwen V Childs, Melanie C MacNicol","doi":"10.1093/biolre/ioag091","DOIUrl":"https://doi.org/10.1093/biolre/ioag091","url":null,"abstract":"<p><p>To study the effect of low-estrogen and the menopause state upon female pituitary function, we used the 4-vinylcyclohexene diepoxide (VCD)-induced ovarian failure model to gradually reduce serum estradiol (E2) levels. We utilized single-cell RNA sequencing transcriptomics analysis (scRNA-seq) to determine how reduced E2 levels influence pituitary gonadotrope gene expression and cell state, with a focus on potential contributions from pituitary stem cells to gonadotrope population growth. VCD-treated mice were acyclic and exhibited 8-15-fold increases in serum levels of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Serum E2 levels were half those of normally cycling proestrous females. Pituitary scRNA-seq identified two gonadotrope populations based upon distinct gene expression signatures (a higher cell number primary cluster, designated here as GON1 and a smaller cell number secondary cluster, designated GON2). The GON1 population increased in number significantly in low-E2, VCD-treated mice, expressing markers indicative of contributions from pituitary stem cell activation. Both gonadotrope populations showed upregulated genes for canonical pathways supporting mRNA translation and hormone secretion, which correlated well with the high serum gonadotropin levels. Consistent with the high serum gonadotropin levels, Fshb and Lhb mRNAs were increased in whole pituitary samples (RT-qPCR). The pituitary Sox2-positive stem cell population exhibited increased expression of more mature transitional progenitors, including Sox9 mRNA, and showed upregulation of pathways involved in stem cell development and mitotic activity. This model provides insight into the cellular and molecular adaptations of the pituitary to the low-E2, menopausal state, with potential relevance for understanding human perimenopausal and menopausal physiology.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761059","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":"Progesterone supplementation in cattle hastens conceptus development and secretion of pregnancy-associated glycoproteins.","authors":"Lillian X Ehresmann, Florentino P J da-Silva-Junior, Hollis Baroody, Gemma D Dotts, Ellie G Kidwell, Paulo M Bonacim, Jeanette V Bishop, Aydin Guzeloglu, Thomas R Hansen, Rafael R Domingues","doi":"10.1093/biolre/ioag088","DOIUrl":"https://doi.org/10.1093/biolre/ioag088","url":null,"abstract":"<p><p>Post-ovulatory supplementation of progesterone (P4) to cows has been associated with enhanced conceptus elongation. The aim of the present study was to investigate the impact of P4 supplementation on peri-implantation conceptus signaling including the secretion of interferon tau (IFNT), the maternal response to IFNT (mRNA abundance of interferon-stimulated genes [ISG; ISG15 and MX2]), and circulating pregnancy-associated glycoproteins (PAG). Two cohorts (A and B) of primiparous Angus beef cows were synchronized to estrus, artificially inseminated (d0), and assigned randomly to receive intravaginal P4 device (CIDR, 1.38 mg) from d3 to d12 or remain as untreated controls. Blood and cervical cytobrush were collected from d3 to d24 and a uterine cytobrush was collected on d24 from Cohort A to assess circulating concentrations of P4, PAG, mRNA abundance of ISG, and concentrations of IFNT, respectively. Blood and cytobrush (cervical and uterine) were collected from Cohort B on d18 to assess circulating concentrations of P4, mRNA abundance of ISG, and concentrations of IFNT, respectively. The mRNA abundance of ISG was assessed in luteal biopsies on d18 and d22. There was no effect of P4 supplementation on concentrations of IFNT in the uterus on d18. There was no effect of supplemental P4 on mRNA abundance or timing of ISG in endometrial, cervical, or luteal tissue. The earlier detection of PAG in circulation and lower uterine fluid concentrations of IFNT on d24 in P4-supplemented cows suggests advanced trophoblast differentiation and enhanced conceptus development beyond previously reported advances in conceptus elongation alone.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761092","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":"Arsenic disturbs spermatogenesis via disrupting Sertoli cell junctions in mice: potential involvement of the TGF-β3/p38 MAPK pathway.","authors":"Xiujuan Li, Liang Zhao, Ziyi Yan, Liqun Huang, Guoli Chai, Wenting Wang, Yanyan Zhang, Zhizhen Liu, Guiqin Yan, Jun Xie","doi":"10.1093/biolre/ioag085","DOIUrl":"https://doi.org/10.1093/biolre/ioag085","url":null,"abstract":"<p><p>Environmental arsenic (As) exposure impairs spermatogenesis and testicular function, but the underlying mechanism remains unclear. In this study, 6-week-old male mice and rat primary Sertoli cells were utilized to explore the mechanism of arsenic-induced spermatogenic impairment. Serum testosterone levels were measured, testicular histology and ultrastructure were assessed, and the expression of tight junction (TJ) proteins, actin-related proteins, cytokines, and key components of the MAPK pathway were further investigated. Our results indicated that arsenic exposure reduced sperm quality, altered histological structure of the testis, and impaired TJs and actin cytoskeleton in the spermatogenic epithelia. Further analysis demonstrated that arsenic suppressed the expression of TJ proteins (CLAUDIN-11, ZO-1) in both testis tissues and primary Sertoli cells. The mRNA level and localization of the actin-related protein (ARP3) were also altered following arsenic exposure. Additionally, arsenic treatment markedly elevated testicular levels of the cytokines IFN-γ and TGF-β3. The gene expression and phosphorylation level of p38 Mapk were significantly increased in arsenic-exposed mice. These findings demonstrate that interference with Sertoli cell junctions is an important factor in arsenic-induced spermatogenic dysfunction. TJ barrier permeability and F-actin realignment, which might be mediated by TGF-β3/p38 MAPK pathway, collectively contribute to the disruption of cell junction structure.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761064","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}