Biology of Reproduction最新文献

{"title":"RUNX proteins and CBFβ create an interconnected network of transcriptional regulation in the male germline†.","authors":"Mustika Rahmawati, Carson J Black, Danika D Dalvi, Amanda J Brown, Kassie M Stadler, Tia M Hoisington, Nathan C Law","doi":"10.1093/biolre/ioag021","DOIUrl":"10.1093/biolre/ioag021","url":null,"abstract":"<p><p>The foundation for lifelong spermatogenesis depends on a highly coordinated program of prepubertal germline development, during which a precise balance between spermatogonial proliferation and differentiation is established to ensure sustained spermatogenesis. Any disruptions to this balance can impair germ cell maturation and overall fertility. However, factors critical in maintaining this balance remain incompletely understood. Our previous studies revealed that core-binding factor subunit-β (CBFβ) regulates both proliferation and differentiation during the onset of spermatogenesis. Canonically, CBFβ functions as a co-factor for the Runt-related transcription factor (RUNX) family by forming heterodimeric complexes that can act either as transcriptional activators or repressors. Here, we reveal interactions between CBFβ and RUNX proteins within the male germline and highlight distinct expression patterns of RUNX1 and RUNX3, particularly differential temporal expression during discrete cell cycle phases within spermatogonia. Moreover, Cleavage Under Targets & Release Using Nuclease (CUT&RUN) analyses revealed both overlapping and distinct genomic localization of RUNX1 and RUNX3. Surprisingly, knockdown studies determined that RUNX1 and RUNX3 act in opposition as either transcriptional activators or repressors within overlapping genomic targets. By contrast, genomic regions with differential RUNX1 or RUNX3 localization suggest distinct regulation of proliferation or differentiation, respectively. Furthermore, motif analysis revealed enrichment of disparate transcription factor motifs, including canonical regulators of the germline. Collectively, our findings suggest that CBFβ, RUNX1, and RUNX3 participate in a network to precisely coordinate proliferation and differentiation during prepubertal germline development, thus ensuring continuous spermatogenesis and male fertility.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1324-1342"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028128","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":"Hypoxanthine is involved in promoting the activation of mouse primordial follicles†.","authors":"Ying Wei, Weiyong Wang, Huiyu Liu, Tiantian Hao, Yan-Li Sun, Shuang Liu, Hongwei Wei, Wenbo Zhang, Xiaodan Zhang, Meijia Zhang","doi":"10.1093/biolre/ioag007","DOIUrl":"10.1093/biolre/ioag007","url":null,"abstract":"<p><p>In each wave, only a small portion of primordial follicles are selectively activated into the growing follicular pool, and the majority of primordial follicles remain in a relatively quiescent state. Hypoxanthine is present in the follicular fluid with high concentrations and inhibits phosphodiesterase activity. In this study, hypoxanthine synthase purine nucleoside phosphorylase (Pnp) was expressed in oocytes, and its expression levels increased progressively with oocyte growth, accompanied by an increase in ovarian hypoxanthine levels. Ovarian hypoxanthine levels were significantly increased in equine chorionic gonadotropin-primed mice, accompanied by an increase in primary follicle numbers. Hypoxanthine significantly increased the number of growing follicles and the levels of cyclic adenosine monophosphate (cAMP) and phosphorylated protein kinase B (p-Akt) in cultured ovaries. Hypoxanthine with intraperitoneal injection in neonatal mice also significantly increased growing follicle numbers and p-Akt protein levels in the ovaries. Additionally, oral BCX-1777 in adolescent mice, a PNP inhibitor, significantly decreased hypoxanthine levels and growing follicle numbers in the ovaries. Thus, hypoxanthine promotes mouse primordial follicle activation through cAMP-PI3K/Akt pathway. The high levels of hypoxanthine produced by the preovulatory fully-grown oocytes may contribute to the promotion of the cyclic activation of primordial follicles.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1371-1382"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951322","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 relationship between seminal microbiome and male reproductive wellness: a systematic review†.","authors":"Baharan Bazzar, Elmira Reshadfar, Parham Namdar, Donya Pourbagher, Rastin Bakhtiari Lafmejani, Ali Soleimanzadeh","doi":"10.1093/biolre/ioag003","DOIUrl":"10.1093/biolre/ioag003","url":null,"abstract":"<p><p>The seminal microbiome, which is composed of different types of bacteria in semen and seminal plasma, has a significant impact on male reproductive health by changing the quality of semen and fertility. Previously regarded as sterile, the male reproductive tract contains microbes originating from the gastrointestinal tract, reproductive organs, and external sources such as sexual partners. Dysbiosis alters sperm parameters, triggers inflammation and oxidative stress, and is associated with conditions such as infertility, HPV infection, prostatitis, prostate cancer, and azoospermia. This systematic review adhered to the PRISMA 2020 guidelines (with 2025 extensions for reproducibility) and examined studies from PubMed, Scopus, and Science Direct (2015-2025, with prior context), concentrating on human, in vitro, and rodent models. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes are among the most important phyla. Beneficial genera, such as Lactobacillus, improve sperm motility, concentration, and DNA integrity, whereas dysbiotic taxa, such as Prevotella, Pseudomonas, and Ureaplasma, are associated with declines. Sexual activity facilitates bidirectional microbial transfer, modifying diversity and fostering the dysbiosis. Inflammatory cytokines, reactive oxygen species, and metabolic disruptions are all involved in this process. Changes that are specific to a disease, such as higher levels of Fusobacterium in HPV-positive samples, worsen the situation. This review highlights how the microbiome alters sperm function and causes infertility. Standardized methods and long-term studies are needed to prove causality. Probiotics and other therapeutic interventions show promise in restoring balance and boosting fertility.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1151-1167"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084012","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":"CXCL12 promotes EMT-mediated malignant transformation of endometriosis-associated ovarian cancer via PI3K/Akt signaling: an integrated transcriptomic and clinical study.","authors":"Xiaochuan Yu, Lijuan Shi, Zhibo Qi, Qi Chen, Yating Zhang, Huali Wang","doi":"10.1093/biolre/ioag016","DOIUrl":"10.1093/biolre/ioag016","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis-associated ovarian cancer is a distinct form of epithelial ovarian cancer that arises from the malignant transformation of benign endometriotic lesions. While epithelial-mesenchymal transition is acknowledged as a crucial process in the progression of endometriosis-associated ovarian cancer, the upstream regulatory mechanisms and key molecular drivers are not fully understood.</p><p><strong>Methods: </strong>Differentially expressed genes between benign endometriosis and endometriosis-associated ovarian cancer (EAOC) tissues were identified using Gene Expression Omnibus datasets. The functional role of stromal cell-derived factor-1 (SDF-1) was investigated through in vitro overexpression and knockdown models. Mechanistic studies focused on SDF-1 interaction with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and regulation of epithelial-mesenchymal transition (EMT)-associated proteins. A retrospective analysis of 38 EAOC patients was performed to evaluate the association between SDF-1 expression and prognosis.</p><p><strong>Results: </strong>SDF-1 expression was significantly elevated in EAOC tissues compared with benign endometriosis and correlated with EMT-related phenotypes. Functional assays demonstrated that SDF-1 enhanced cellular migration and invasion capacities. Mechanistically, SDF-1 induced EMT through activation of the PI3K/AKT signaling pathway. Clinically, high SDF-1 expression was associated with reduced overall survival and increased recurrence risk. Multivariate Cox regression analysis identified SDF-1 as an independent adverse prognostic factor in EAOC.</p><p><strong>Conclusions: </strong>This study systematically elucidates the critical role of SDF-1 in the malignant transformation of endometriosis to EAOC. SDF-1 promotes tumor invasion and metastasis via PI3K/AKT-mediated induction of EMT. These findings highlight SDF-1 as a promising biomarker for early diagnosis and a potential therapeutic target, offering novel avenues for precision management of EAOC.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1383-1399"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987974","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":"In vitro and in vivo treatment with propranolol influences the number of early preantral follicles in mice†.","authors":"Stella Pollyanne Oliveira, Camila Stefane Ferreira, Emily Joy Zaniker-Gomez, Mariam Charles, Larissa Aline Freitas, Franciel Batista Felix, Luiza Aparecida Ansaloni Chagas Pereira, Whocely Victor de Castro, Vanessa Pinho, Francesca E Duncan, Paulo Henrique Almeida Campos-Junior","doi":"10.1093/biolre/ioag024","DOIUrl":"10.1093/biolre/ioag024","url":null,"abstract":"<p><p>Stimulating follicle growth could have utility for fertility preservation before follicular culture or as part of ovarian stimulation protocol therapies for women with a limited ovarian reserve. Propranolol is a clinically approved beta-blocker. Beyond its beta-adrenergic receptors, recent investigations have suggested an alternative role in activating Mammalian target of rapamycin (mTOR). Therefore, this study aimed to evaluate the efficacy of propranolol treatment on early follicle growth, both in vitro and in vivo. For in vitro studies, neonatal mouse ovaries were cultured for up to 3 days in the presence or absence of propranolol and then processed for histological analysis, quantitative PCR (qPCR), RNA in situ hybridization, and western blot (WB). For in vivo experiments, mice were treated with a low or a high dose of propranolol or no drug for 15 days. Then, analyses were performed, including body and ovarian weight measurements, histological analyses, WB, and qPCR. In vitro experiments demonstrated that treatment decreased primordial follicles and increased transitional, primary, and secondary follicles. Consistent with this, propranolol treatment resulted in the downregulation of Pten and an increased presence of Cpeb1, a novel biomarker of follicle activation, in primordial follicles. In our in vivo studies, propranolol promoted follicle activation, increased PI3K-p110 levels, and decreased Pten expression. In summary, propranolol increases the transition of primordial follicles to more advanced stages of development. These findings highlight propranolol as a potential drug to induce, in vivo and in vitro, early preantral follicle growth, potentially improving fertility preservation techniques and studies.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1429-1444"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146059796","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":"Fertilization with Protamine-2 deficient sperm triggers abnormal pronucleus development and zygotic cleavage†.","authors":"Shannon R Rainsford, Kevin Tse, Benjamin William Walters, Jong-Nam Oh, Kaelyn Sumigray, Bluma J Lesch, Zachary D Smith","doi":"10.1093/biolre/ioag010","DOIUrl":"10.1093/biolre/ioag010","url":null,"abstract":"<p><p>Spermatozoan DNA is hyper-condensed by protamines, which are essential for sperm motility and function. Since defects in this process impact natural fertilization, little is known about how changes to protamine-mediated condensation impact the oocyte's ability to recognize and reprogram the paternal genetic material for the early stages of embryogenesis. Here, we performed intracytoplasmic sperm injection (ICSI) with sperm lacking Protamine 2 (Prm2 KO) and tracked preimplantation development in mice. We found that ICSI with Prm2 KO sperm leads to embryo fragmentation and arrest at the 2-cell stage. Surprisingly, injected Prm2 KO sperm DNA is rapidly depleted from the oocyte during the completion of maternal meiosis II, leading to a zygote with one morphologically abnormal pronucleus. Direct induction of DNA damage in wild type sperm did not recapitulate the pronuclear abnormalities found in Prm2 KO-derived zygotes. Co-injection with wild type sperm failed to rescue these defects, indicating that they were not caused by absence of a normally protaminated paternal genome. Finally, we find that testicular Prm2 KO sperm support progression to the blastocyst stage, suggesting a model where fertility-compromising factors are acquired during epididymal maturation. Our results demonstrate that Protamine 2 is necessary for correct maturation of epididymal sperm and essential for their ability to form a functional zygote at fertilization.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1210-1226"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008589","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":"Loss of the maternal effect gene NLRP2 impairs embryonic and extra-embryonic development, revealing a novel genetic cause of congenital anomalies†.","authors":"Momal Sharif, Zahra Anvar, Imen Chakchouk, Sara H El-Dessouky, Roni Zemet, Eric C Kao, Wessam E Sharaf-Eldin, Ying-Wooi Wan, Zhandong Liu, Pengfei Liu, Michael Jochum, Ignatia B Van den Veyver","doi":"10.1093/biolre/ioaf290","DOIUrl":"10.1093/biolre/ioaf290","url":null,"abstract":"<p><p>Maternal effect genes (MEGs) play a crucial role in early mammalian development, and their dysfunction can lead to severe embryonic and extra-embryonic abnormalities. NLRP2, a MEG that encodes a subcortical maternal complex protein, has been implicated in preimplantation development, but its role after implantation remains underexplored. In this study, we investigated the developmental consequences of maternal Nlrp2 loss-of-function in a maternal knockout (KO) mouse model at embryonic day 11.5. Embryos derived from Nlrp2-KO females have abnormal yolk sac vasculature, increased embryonic resorption, craniofacial abnormalities, neural tube defects, and congenital heart defects. Placental architecture is disrupted with an altered junctional zone and labyrinth structure. Transcriptome profiling of maternal decidua and placenta demonstrated dysregulation of genes involved in trophoblast differentiation and extra-embryonic development. Bisulfite sequencing of these tissues revealed persistence at E11.5 of previously observed locus-specific disruption in DNA methylation at four imprinted loci following maternal Nlrp2 loss. We further describe pregnancy outcomes and offspring phenotypes for two unrelated women with bi-allelic maternal NLRP2 variants. The first carried homozygous NLRP2 nonsense variants and experienced recurrent pregnancy loss and fetuses with multiple structural anomalies, including omphalocele, craniofacial dysmorphism, and cardiac defects. The second carried compound heterozygous frameshift and missense NLRP2 variants and had a child with neurodevelopmental impairment of uncertain etiology. These findings indicate a conserved role for maternal NLRP2 in embryonic viability and placental development, and support further studies in humans into the contribution of NLRP2 and other similar MEGs to offspring congenital anomalies and adverse pregnancy outcomes.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1469-1485"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846444","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":"The embryo-derived protein PDI is highly conserved among placental mammals and alters the endometrial transcriptome and secretome in vitro across species with differing implantation strategies†.","authors":"Haidee Tinning, Alysha Taylor, Dapeng Wang, Anna Pullinger, Georgios Oikonomou, Miguel A Velazquez, Paul Thompson, Achim Treumann, Peter T Ruane, Mary J O'Connell, Niamh Forde","doi":"10.1093/biolre/ioaf263","DOIUrl":"10.1093/biolre/ioaf263","url":null,"abstract":"<p><p>Pregnancy establishment in mammals requires a complex sequence of events, including bi-lateral embryo-maternal communication, leading up to implantation. This is the time when most pregnancy loss occurs in mammals (including humans and food production species) and dysregulation in embryo-maternal communication contributes to pregnancy loss. Embryo-derived factors modify the function of the endometrium for pregnancy success. We hypothesise that these previously unexplored conceptus-derived proteins may be involved in altering the function of the endometrium to facilitate early pregnancy events in mammals with different early pregnancy phenotypes. Here, we show that protein disulphide-isomerase (PDI) is a highly conserved protein among mammals and provide evidence for a species-specific role for PDI in endometrial function in mammals with different implantation strategies. We show how PDI alters the endometrial transcriptome in human and bovine in vitro in a species-specific manner and using a microfluidic approach we demonstrate that it alters the secretome capability of the endometrium. We also provide evidence from in vitro assays using human-derived cells that MNS1, a transcript commonly downregulated in response to PDI in human and bovine endometrial epithelial cells, may be involved in the attachment phase of implantation. We propose that the trophoblast-derived protein PDI, is involved in supporting the modulation of the uterine luminal fluid (ULF) secreted by the endometrium to support conceptus nourishment, and in the process of embryo attachment to the uterine lumen for pregnancy success in mammals.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1295-1311"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666963","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":"RNA exosome component EXOSC10 variants identified in a patient with premature ovarian insufficiency†.","authors":"Brianna L Kline, Izaac L Moran, Xuebi Cai, Nicole A Siddall, Fernando Wijaya, Jerome Dulon, Shabnam Bakhshalizadeh, Katrina M Bell, Sylvie Jaillard, Gorjana Robevska, Jocelyn A van den Bergen, Philippe Touraine, Katie L Ayers, Gary R Hime, Andrew H Sinclair, Elena J Tucker","doi":"10.1093/biolre/ioag020","DOIUrl":"10.1093/biolre/ioag020","url":null,"abstract":"<p><p>Premature ovarian insufficiency (POI) impacts ~1%-3.7% of women under the age of 40 globally and is characterised by an absence or complete loss of ovarian function. POI is clinically heterogenous in nature and researchers have identified >100 causative genes harbouring variants responsible for POI thus far. Genes identified to date include those associated with cell differentiation/development, mitochondrial maintenance, hormone receptors, transcription/translation factors, DNA repair/replication, and metabolic processes. Genes encoding cell components that facilitate these processes should therefore be considered in POI gene candidature. The RNA exosome is a critical component in RNA processing, degradation, and biogenesis in eukaryotic cells. Catalytic activity of the RNA exosome is supplied by two subunits, DIS3 and EXOSC10. Dysregulation of RNA exosome function results in conditions known as exosomopathies that have a broad spectrum of phenotypic severity. RNA transcript regulation is essential in transcriptionally inactive maturing mammalian oocytes with its disruption negatively impacting meiosis and fertilization. Notably, oocyte depletion of Exosc10 significantly impacts the fertility of female mice. Herein we identified, via whole exome sequencing, the first instance of a human POI patient with an EXOSC10 homozygous missense variant. Using Drosophila melanogaster we modelled the impact of knockdown of the EXOSC10 ortholog, Rrp6, on both somatic and germline ovarian cells. We observed that Rrp6 is required in ovarian development in Drosophila. Due to the conserved role of EXOSC10 in fertility maintenance across species we contend that variants in EXOSC10 identified in POI patients may be causative.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1416-1428"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13079453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084015","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":"Soma-sperm communication during the journey to fertilization: addressing challenges and opportunities†.","authors":"Raissa Braido Rangel, Ana Beatriz Bossois Moura, Laura Gabrielli Haupenthal, Luca Angi Souza, Maria Alice de Almeida, Juliano Coelho da Silveira, Felipe Perecin, Maíra Bianchi Rodrigues Alves","doi":"10.1093/biolre/ioaf277","DOIUrl":"10.1093/biolre/ioaf277","url":null,"abstract":"<p><p>Male infertility is a significant concern in both human medicine and livestock. As it is mainly impacted by sperm quality, understanding the intrinsic characteristics of sperm that contribute to infertility is crucial. Male fertility relies on the sperm's ability to reach the site of fertilization, fertilize the oocyte, and support early embryonic development. Thus, classical sperm parameters such as motility, morphology, and the integrity of the plasma membrane, acrosome, and DNA are critical indicators of sperm quality. Recently, molecular sperm features have also been recognized as key components of sperm quality. Although sperm are transcriptionally inert and rely on external factors to shape their molecular cargo, \"sperm-borne\" RNAs and proteins impact embryo development. Sperm-borne molecules are acquired as sperm transit through the male and, potentially, female reproductive tracts, where they interact with components, including extracellular vesicles (EVs) from fluids within both systems. EVs play a key role in intercellular communication and carry regulatory molecules, such as proteins and miRNAs, that modulate sperm function. These interactions are vital for spermatogenesis, maturation, capacitation, and influence the sperm-borne molecular cargo. Since sperm remain interacting with the female tract, it is evident that sperm's fertility potential is also outlined in the post-ejaculatory environment. This review provides an overview of these interactions, particularly within the female reproductive system where EVs participate in sperm-borne modulation, sperm capacitation and might also be involved in sperm selection. Herein, we provide insights for further research into the mechanisms involved and their effects on sperm fertilizing potential across mammalian species.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1130-1150"},"PeriodicalIF":3.0,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145848855","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}