Reproduction最新文献

{"title":"ROCK inhibitor Y-27632 improves embryo transfer pregnancy rates following cryopreservation of biopsied embryos.","authors":"Yubing Wang, Ke Li, Jia Hao, Xingyuan Liu, Dayong Chen, Lei Cheng, Lei An, Jianhui Tian, Guangyin Xi","doi":"10.1093/reprod/xaag102","DOIUrl":"10.1093/reprod/xaag102","url":null,"abstract":"<p><p>In brief: Embryo biopsy and cryopreservation compromise pregnancy rates, limiting genetic testing in livestock and humans. This study shows that Y‑27632 improves post‑thaw embryo quality and increases pregnancy rates in biopsied sheep embryos. Abstract: Preimplantation genetic testing relies on embryo biopsy, yet biopsied embryos exhibit reduced cryotolerance and compromised post-thaw viability. In this study, we optimized biopsy parameters and explored cryoprotective strategies in sheep embryos. Trophectoderm biopsy at a position two-thirds distant from the inner cell mass yielded optimal cell numbers (21.96 ± 1.21 cells) while maintaining high postbiopsy re-expansion rates (92.56%). An 8-hr postbiopsy recovery period prior to vitrification was identified as optimal, achieving complete re-expansion with minimal apoptosis while avoiding progression to hatched stages unsuitable for transfer. Supplementation with 10 μM Y-27632 at different vitrification stages was assessed for effects on re-expansion, cell viability, apoptosis, and pregnancy rates after transfer. Transcriptomic profiling revealed that Y-27632 effectively suppressed lipid and sterol biosynthesis, shifting metabolism toward energy conservation pathways that enhance cryoresistance. Treated embryos also showed significantly reduced lipid droplet accumulation, confirming metabolic remodeling. Y-27632 administration, particularly before and after vitrification, markedly improved cryotolerance, developmental capacity, and pregnancy outcomes of biopsied embryos, increasing pregnancy rates from 24.3% to 37.2%. These findings establish an optimized biopsy and recovery protocol and identify molecular changes associated with the protective effects of Y-27632 by which Y-27632 enhances embryo cryotolerance, presenting a practical strategy to improve cryopreservation efficacy in livestock and human-assisted reproduction.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate ovarian aging by inhibiting ferroptosis.","authors":"Chia-Jung Li, Li-Te Lin, Pei-Hsuan Lin, Boyang Wang, Zhi-Hong Wen, Kuan-Hao Tsui","doi":"10.1093/reprod/xaag104","DOIUrl":"10.1093/reprod/xaag104","url":null,"abstract":"<p><p>In brief: Ovarian aging and the resulting decline in oocyte quality remain significant challenges for female reproductive health and fertility. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes can partially improve ovarian aging-associated phenotypes by activating NRF2-mediated antioxidant defenses and inhibiting ferroptosis, offering a promising cell-free therapeutic strategy. Abstract: Ovarian aging is characterized by a decline in oocyte quantity and quality, often driven by oxidative stress and cellular damage. Human umbilical cord mesenchymal stem cell-derived exosomes (hUC-MSC-Exos) have emerged as a potent cell-free therapy for regenerative medicine. In this study, female mice with early ovarian aging (31-33 weeks; n = 8 per group) received 10 intraperitoneal injections of hUC-MSC-Exos (240 µL/dose, 6.5 × 10¹⁰ particles/mL) over 2 weeks. Ovarian function, follicular development, DNA damage, and ferroptosis-related markers were evaluated. hUC-MSC-Exo treatment significantly increased the number of primary and antral follicles without a significant change in primordial follicle counts. Exosome administration reduced genomic stress, evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) intensity, and improved oocyte yield and mitochondrial metabolic state. Mechanistically, hUC-MSC-Exos promoted the nuclear translocation of Nuclear factor erythroid 2 related factor 2 (NRF2), a master antioxidant regulator. This activation was accompanied by the suppression of ferroptosis, indicated by upregulation of GPX4 and SLC7A11 and downregulation of 4-HNE and ACSL4. Furthermore, exosome treatment restored ovarian functional markers (anti-Müllerian hormone [AMH], BMP15) and steroidogenic proteins (CYP11A1, 3β-HSD, StAR). These findings suggest that hUC-MSC-Exos mitigate age-related ovarian dysfunction by modulating NRF2-mediated antioxidant defenses and inhibiting ferroptosis, offering a promising candidate that warrants validation with functional reproductive endpoints.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C/EBPδ regulates SPHK1-dependent excessive autophagy in decidualization defects of chronic endometritis.","authors":"Jiahui Xiao, Shuyi Yu, Shiru Xu, Guanying You, Meilan Mo, Ruochun Lian, Cong Chen, Xueling Zhang, Yuye Li","doi":"10.1093/reprod/xaag111","DOIUrl":"10.1093/reprod/xaag111","url":null,"abstract":"<p><p>In brief: Chronic endometritis (CE) impairs endometrial receptivity via unknown mechanisms. This study reveals that suppression of the C/EBPδ-sphingosine kinase 1 (SphK1)-sphingosine-1-phosphate (S1P) axis in CE leads to decidualization defects accompanied by excessive autophagy, providing a mechanistic link between chronic inflammation, sphingolipid dysregulation, and impaired endometrial receptivity. Abstract: Chronic endometritis (CE) is a persistent inflammatory disorder of the endometrium that is increasingly recognized as an important cause of reproductive failure. However, the molecular mechanisms by which CE impairs endometrial receptivity remain incompletely understood. Here, we found that decidualization markers IGFBP1 and PRL were significantly decreased in CE patients, accompanied by abnormal glandular architecture. Transcriptomic analysis revealed sphingolipid metabolism as a dysregulated pathway, with sphingosine kinase 1 (SphK1) markedly downregulated. Sphingosine-1-phosphate (S1P) levels were reduced in both CE tissues and lipopolysaccharide-treated stromal cells during decidualization. Functional experiments confirmed that SphK1 is essential for this process, and its deficiency impairs decidualization. Mechanistically, transcription factor C/EBPδ directly bound and activated the SphK1 promoter. Chronic endometritis endometrium showed reduced C/EBPδ and SphK1, alongside increased LC3B, indicating autophagic dysregulation. Furthermore, S1P was demonstrated to act extracellularly through the G protein-coupled receptor S1P receptor 3 (S1PR3) to maintain autophagic homeostasis, thereby regulating endometrial decidualization. In conclusion, suppression of the C/EBPδ-SphK1 axis impairs decidualization with excessive autophagy, revealing a mechanistic link between chronic inflammation, sphingolipid dysregulation, and reproductive failure.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148907155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic analysis of human and murine endometrial organoids using a machine learning approach.","authors":"Anna Catherine Unser, Genesis J Herrera, Sydney E Parks, Baku Nakakita, Suni Tang, Linda Alpuing Radilla, Brooke Thigpen, Xiaoming Guan, Diana Monsivais","doi":"10.1093/reprod/xaag100","DOIUrl":"10.1093/reprod/xaag100","url":null,"abstract":"<p><p>In brief: Endometrial organoids are a powerful 3D in-vitro system to study reproductive function and disease; however, available models for quantitative analysis of organoids are still developing and have not been assessed for endometrial organoids. This paper uses models to reliably segment individual organoids and phenotypically analyze human and murine endometrial organoids. Abstract: Endometrial organoids are a powerful, 3D in vitro system for studying reproductive function and disease since they are more physiologically representative than 2D cell models. However, optimal methods for the analysis of individual organoids are still developing and remain inconsistent throughout the field. To independently evaluate and optimize high-throughput analysis tools for human and mouse endometrial organoids, we first assessed several interfaces-OrganoID, OrganoSeg2, and Biodock-for their segmentation capabilities of whole-dome Z projection brightfield microscopy images. The edge detections of OrganoID and OrganoSeg2 were not sufficient to distinguish individual endometrial organoids when multiple organoids were in contact or when debris was present and thus, we did not further evaluate these interfaces for phenotypic quantitative analysis. By creating trained deep learning models on Biodock which performed reliable segmentation, we present methods to classify and quantify organoids with mixed \"round\" or \"abnormal\" populations, extracting critical information such as area, eccentricity, and brightness from each individual organoid. These analysis parameters were effective in organoids from human endometrial epithelium grown in complete vs reduced medium and from genetically engineered mice. Additionally, Biodock was used to quantify live and dead cells labeled with fluorescent dyes, showing that it is also useful for quantifying high-throughput live imaging data from drug treatment experiments. Overall, deep learning models trained through Biodock accurately assessed phenotypic properties of human and murine endometrial organoids in brightfield and live-fluorescent microscopy, demonstrating that it is a promising tool for analyzing endometrial organoids to reliably detect phenotypic differences from organoid microscopy.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Ketoglutarate enhances epigenetic remodeling and developmental competence in porcine SCNT embryos.","authors":"Baobao Zhao, Jieyu Wang, Zihan Xu, Xiaoli Guo, Shiqing Wang, Zhenzhen Yin, Yang Li, Meiyun Lv, Jinwang Liu, Heqiang Li, Suzhu Qing, Yongsheng Wang","doi":"10.1093/reprod/xaag103","DOIUrl":"10.1093/reprod/xaag103","url":null,"abstract":"<p><strong>In brief: </strong>Zygotic genome activation failure contributes to the low developmental efficiency of porcine somatic cell nuclear transfer (SCNT) embryos. We show that α-ketoglutarate improves transcriptional activation, epigenetic remodeling, and embryo development in SCNT embryos, supporting its potential use for improving nuclear reprogramming efficiency.</p><p><strong>Abstract: </strong>Abstract: Incomplete zygotic genome activation (ZGA) is a major barrier limiting the developmental competence of somatic cell nuclear transfer (SCNT) embryos in pigs. α-Ketoglutarate (α-KG), a key metabolic intermediate and cofactor for α-KG-dependent dioxygenases, has been implicated in epigenetic remodeling during early embryogenesis. In this study, we investigated whether α-KG supplementation could improve developmental potential and ZGA-associated events in porcine SCNT embryos. Treatment with α-KG improved cleavage progression, increased blastocyst formation rates, increased total blastocyst cell number and inner cell mass cell number, and reduced apoptosis and DNA damage. In addition, α-KG improved microtubule organization and actin distribution during early cleavage stages, contributing to more coordinated cell division. Mechanistically, α-KG increased global 5-hydroxymethylcytosine (5hmC) levels and elevated the abundance of activating histone marks, including H3K4me3 and H3K27ac. Expression of several ZGA-associated genes, including DUXA, ZSCAN4, EIF1A, and KLF17, was significantly increased following α-KG supplementation, accompanied by enhanced nascent RNA synthesis. Notably, inhibition of TET enzymes with Bobcat339 attenuated the effects of α-KG on 5hmC accumulation, transcriptional activity, and embryo development. Collectively, these findings indicate that α-KG improves developmental competence and is associated with enhanced epigenetic remodeling in porcine SCNT embryos, at least in part through TET-associated pathways, providing a potential strategy for improving nuclear reprogramming efficiency in animal cloning.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal progesterone: impacts on conceptus development and conceptus-maternal interactions.","authors":"Lillian X Ehresmann, Rafael R Domingues","doi":"10.1093/reprod/xaag098","DOIUrl":"10.1093/reprod/xaag098","url":null,"abstract":"<p><p>In brief: Maternal progesterone modulates the uterine environment that governs conceptus elongation, signaling, and implantation in cattle, yet supplementation strategies inconsistently improve pregnancy success. This review synthesizes current understanding of progesterone-regulated conceptus-maternal interactions and highlights the use of longitudinal biomarkers (IFNT, ISG, and PAG) to better resolve how progesterone influences early pregnancy establishment. Abstract: Progesterone is the key maternal hormone regulating uterine function during early pregnancy to support the developing conceptus and promote uterine receptivity. In turn, the conceptus acquires the capacity to signal its presence and further modulates a maternal response to allow for attachment and initiation of placentation. Supplementation of progesterone is proposed to optimize conceptus-maternal interactions and favor pregnancy establishment due to advanced temporal changes in the uterine milieu allowing for hastened conceptus elongation. Nevertheless, supplemental progesterone has not consistently increased pregnancy per service when applied in beef or dairy cattle, indicating that further research is required. Beyond increasing conceptus elongation, the extent to which supplemental progesterone impacts conceptus development and signaling to favor pregnancy establishment remains poorly understood. Evaluation of interferon tau, interferon-stimulated genes, and pregnancy-associated glycoproteins can be used to infer about the progression of the conceptus through key developmental milestones but has not been widely applied in the context of progesterone supplementation. Importantly, assessment of these conceptus- and pregnancy-specific biomarkers may be performed in vivo and can provide more adequate insight into the timing of conceptus-maternal interactions in response to supplementation of progesterone, especially when examined temporally.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial effects of melatonin on mouse preimplantation embryo development and implantation potential: possible involvement of clathrin-mediated endocytosis.","authors":"Yue Li, Zhiqi Wang","doi":"10.1093/reprod/xaag105","DOIUrl":"10.1093/reprod/xaag105","url":null,"abstract":"<p><p>In brief: Embryo implantation is a critical determinant of reproductive success, yet improving the implantation potential of in vitro-cultured embryos remains a major challenge in assisted reproductive technology. This study demonstrates that melatonin promotes mouse preimplantation embryo development and implantation potential and provides evidence that CME-related processes may contribute to these beneficial effects. Abstract: Melatonin is a pleiotropic hormone with essential roles in mammalian reproduction. Our previous study demonstrated that melatonin promotes human oocyte maturation and early embryo development through enhancement of clathrin-mediated endocytosis (CME). In the present study, we investigated whether a similar melatonin-associated regulatory relationship is also observed during mouse preimplantation embryo development and implantation. Following concentration optimization, mouse zygotes were cultured with 10-9 M melatonin, 20 μM dynasore (a pharmacological inhibitor of dynamin-dependent endocytosis), or their combination. Melatonin supplementation significantly increased blastocyst formation and subsequent implantation potential. Conversely, dynasore treatment reduced blastocyst developmental progression and markedly impaired implantation potential. Importantly, melatonin supplementation significantly improved the implantation potential of dynasore-treated embryos. These findings demonstrate that melatonin promotes mouse preimplantation embryo development and implantation potential, and suggest that CME-related processes may contribute to these beneficial effects. Together with our previous findings in human oocytes and early embryos, the present study provides evidence supporting a shared melatonin-associated regulatory relationship between human and mouse reproductive systems. Given that suboptimal embryo implantation remains a major limitation in assisted reproductive technology, our findings suggest that melatonin supplementation warrants further investigation as a potential strategy for optimizing in-vitro embryo culture conditions and improving implantation outcomes.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacillus maritimus strain N2 promotes testicular molecular signatures in Bohai Black cattle by remodeling the rumen microbiota-host metabolic axis.","authors":"Yan-Ni Feng, Pei-Yu Dong, Zhuang-Bing Li, Yang Dong, Yin-Yin Li, Lei Yang, Xin-Lei Feng, Chao Qi, Shu-Er Zhang, Xi-Feng Zhang","doi":"10.1093/reprod/xaag108","DOIUrl":"10.1093/reprod/xaag108","url":null,"abstract":"<p><p>In brief: Restricting feed antibiotics in ruminant breeding urgently demands probiotic strategies to mitigate environmental toxin-induced male reproductive impairment, yet the rumen-testis axis interorgan regulatory mechanisms of marine-origin bacilli remain largely uncharacterized. This study establishes a novel cross-organ axis mediated by Bacillus maritimus N2 enriches ruminal anti-inflammatory Adlercreutzia, reducing circulating phenolic pro-oxidants while elevating serum quercetin, thereby activating testicular oxidative phosphorylation and tight-junction programmes. This rumen-testis axis boosts steroidogenesis, germ-cell development, and blood-testis barrier integrity in Bohai Black cattle, supporting microbial-targeted bull fertility regulation. Abstract: Probiotics have attracted significant attention as a potential strategy to improve testicular molecular signatures relevant to reproduction in ruminants. In this study, Bohai Black cattle were used as a model to systematically elucidate the mechanisms by which Bacillus maritimus strain N2 positively modulates testicular transcriptomic and metabolic signatures through multiomics techniques. The study found that feeding N2 to the cattle specifically enriched the rumen with Adlercreutzia bacteria, which have anti-inflammatory potential, and markedly reduced levels of pro-oxidant toxins, such as phenolic derivatives, in the host circulatory system, accompanied by an increase in the antioxidant metabolite quercetin. Integrated analysis indicated that these metabolic changes were closely associated with a testicular gene coexpression module enriched for oxidative phosphorylation. Ultimately, N2 intervention significantly enhanced the expression of key protein markers involved in steroid synthesis, germ-cell development, and blood-testis barrier integrity in the testes. This study is the first to depict a cross-organ regulatory axis of probiotics through enriching rumen Adlercreutzia-remodeling host metabolic profile-activating testicular energy and barrier programs, providing an important mechanistic example for a deeper understanding of rumen-testis axis interactions.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148866821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Failures to maintain CpG-methylation of CoRSIVs in bovine sperm are associated with low sire conception.","authors":"Eyal Seroussi, Jiarui Cai, Li Ma, Moran Gershoni","doi":"10.1093/reprod/xaag099","DOIUrl":"10.1093/reprod/xaag099","url":null,"abstract":"<p><p>In brief: Correlated regions of systemic interindividual epigenetic variation (CoRSIVs) are genomic regions with CpG-methylation patterns that differ between individuals, yet are consistent between tissues, within the same individual. Analyzing two groups of Holstein bull methylomes-nine with a high sire-conception rate (SCR) and nine with a low SCR-we found that a common type of CoRSIVs was significantly associated with reduced SCR and is thus suggested as a biomarker for SCR because it was highly methylated in sperm, but failed to retain hypermethylation in the gametes of males with low SCR. Abstract: Correlated regions of systemic interindividual epigenetic variation (CoRSIVs) are genomic regions with CpG-methylation patterns that differ between individuals, yet are consistent between tissues, within the same individual; therefore, their methylation can be profiled in bodily fluids that are easily obtained, such as blood and semen. Bearing in mind the simple epigenetic profiling of CoRSIVs, we tested whether this type of differentially methylated region (DMR) is associated with bovine fertility. Sequence Read Archive (SRA) meth BLAST was used to estimate CoRSIVs methylation status in 18 healthy, representative, and age-matched Holstein bulls, among which nine had high (H) sire-conception rate (SCR), and the other nine had low (L) SCR (group averages of SCR: 3.3 ± 0.6 and -3.8 ± 1.8, respectively). This method was also applied to morula and trophoblast SRA methylomes. Analysis with meth BLAST was effective for most (80%) CoRSIVs and showed that CoRSIVs are reprogrammed during blastocyst formation, although this method was incapable of specifically determining the methylation level in CoRSIVs with retrotransposons. In sperm, the effect of global methylation was evident in a common (25%) type of CoRSIVs that is highly (94.5% ± 4.3%) methylated in sperm. Specifically, a failure to retain hypermethylation in the sperm plus strand was significantly (p < 0.00025) indicative of low SCR. Comparing global DNA methylation using the latter type of CoRSIVs between sperm and blood can be used as a better biomarker for fertility than using other differentially methylated regions with more complex epigenetics.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adenosine may regulate the integrity of the testicular peritubular wall: evidence from cellular studies.","authors":"Lina Scholz, Michaela Schneider, Frank-Michael Köhn, Matthias Trottmann, Artur Mayerhofer","doi":"10.1093/reprod/xaag106","DOIUrl":"10.1093/reprod/xaag106","url":null,"abstract":"<p><p>In brief: How the integrity of the multilayered human testicular peritubular wall compartment is maintained was unknown. We found that in isolated human testicular peritubular cells, adenosine enhanced the levels of the adherens junction protein cadherin-11, prevented cell migration, and thus may reinforce the structural and functional integrity of the architecture of the human peritubular wall in situ. Abstract: In the human testis, seminiferous tubules are surrounded by several layers of peritubular cells and extracellular matrix. How the integrity of this small compartment is maintained remains unknown. Isolated and cultured human testicular peritubular cells (HTPCs) provide an opportunity to study aspects of the peritubular wall compartment. Previous studies have shown that HTPCs are targeted by extracellular purines, including adenosine. A proteomic analysis revealed that adenosine was negatively linked, among others, to \"(positive) regulation of cell migration\" and \"focal adhesion\" pathways and positively linked to \"single organismal cell-cell adhesion\" pathways. We therefore hypothesized that adenosine may contribute to the integrity of the peritubular wall compartment and tested this in functional assays. We found that adenosine significantly reduced HTPCs migration, accompanied by significantly decreased single-cell velocity, while cell number and proliferation remained unaffected. Changes in cell-cell and cell-substrate adhesion may underlie this effect, pointing to a role for cadherin-11 (CDH11), the major adherens junction protein of HTPCs. Its role in cell motility was shown upon siRNA-mediated knockdown of CDH11, which enhanced HTPC migration. Immunocytochemistry and western blotting revealed that adenosine increased CDH11 protein levels. Involvement of ADORA2B receptors was indicated by a comparable action of the selective adenosine receptor agonist BAY60-6583. Collectively, these results suggest that adenosine, by increasing the abundance of CDH11, suppresses cell migration. If transferable to the in-situ situation, locally produced adenosine may reinforce the structural integrity of the multilayered architecture of the peritubular wall.</p>","PeriodicalId":21127,"journal":{"name":"Reproduction","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148831911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}