Biology of Reproduction最新文献

{"title":"Expression and regulation of nucleoside/nucleobase transporters and the role of adenine at the maternal-conceptus interface in pigs†.","authors":"Yugyeong Cheon, Inkyu Yoo, Soohyung Lee, Eunhyeok Choi, Seonghyun Kim, Minsun Hong, Hakhyun Ka","doi":"10.1093/biolre/ioag150","DOIUrl":"10.1093/biolre/ioag150","url":null,"abstract":"<p><p>Purine nucleosides and nucleobases such as adenine (ADE) and adenosine (ADO) move through cellular transporters and play essential roles in various physiological processes, including proliferation, differentiation, immunity, and pregnancy. The cellular uptake of ADE, ADO, and other purine metabolites via these transporters regulates intracellular nucleotide pools and supports purine salvage pathways, thereby maintaining metabolic homeostasis and cellular function. Although the importance of nucleoside/nucleobase transporters during pregnancy has been studied in some species, their expression and the role of ADE at the maternal-conceptus interface have not been evaluated in pigs. Therefore, we investigated the expression and regulation of nucleoside/nucleobase transporters SLC28As, SLC29As, and SLC43A2 and the function of ADE at the maternal-conceptus interface in pigs. The expression of nucleoside/nucleobase transporters in the endometrium varied dynamically during pregnancy, and the localization of these transporters was cell type-specific. During pregnancy, both conceptus and chorioallantoic tissues expressed nucleoside/nucleobase transporters. Interleukin-1β increased the expression of SLC29A2 and a calcium ionophore decreased the expression of SLC28A2 and SLC29A3 in endometrial explants. Increasing doses of ADE increased the expression of prostaglandin (PG) synthetic enzymes and transporters and cytokines in endometrial epithelial cells and the expression of PG synthetic enzymes and transporters as well as implantation-related genes, and migration of conceptus trophectoderm cells in vitro. These data suggest that the expression of nucleoside/nucleobase transporters is dynamically regulated at the maternal-conceptus interface and ADE may play important roles in regulation of endometrial epithelial and conceptus trophectoderm cell function during the establishment and maintenance of pregnancy in pigs.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1091-1106"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444322","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":"Inflammation, estrogen, and matrix remodeling in female reproductive health: from crosstalk mechanisms to translational diagnostics†.","authors":"Liya Du, Aileen Suarez, Vibhav Jha, Pranav Volety, Carly A Lockard, Bradley P Sutton, Andrew M Smith, Ayelet Ziv-Gal, Bruce M Damon, Indrani C Bagchi, Amy Wagoner Johnson","doi":"10.1093/biolre/ioag156","DOIUrl":"10.1093/biolre/ioag156","url":null,"abstract":"<p><p>The female reproductive system is a hormonally driven, immune-active, and structurally dynamic system in which estrogen signaling, inflammation, and extracellular matrix (ECM) remodeling interact to support essential reproductive processes. Cyclical changes in hormone levels, inflammation, and ECM turnover are essential for normal physiology, but dysregulation of these processes can give rise to chronic inflammation, fibrosis, and dysfunction across multiple reproductive tissues. Chronic immune activation, abnormal estrogen signaling, and maladaptive ECM remodeling engage in positive feedback loops that drive pathologies such as endometriosis, cervicitis, uterine fibroids, and intrauterine adhesions. Integrating preclinical rodent models with clinical findings, this review synthesizes current knowledge on the individual and interconnected roles of inflammation, estrogen signaling, and ECM remodeling and highlights diagnostic tools to improve early detection and therapy. The highlight of diagnostic tools focuses on emerging non-invasive imaging modalities, particularly magnetic resonance-based techniques, for in vivo visualization and quantification of inflammation, fibrosis, and tissue biomechanics in the female reproductive system.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1032-1047"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 modulates decidualization through PPARGC1A and mitochondrial bioenergetics†.","authors":"Fang-Fang Li, Xiao-Yan Chen, Jia-Qi Xu, En-Xiang Chen, Li-Juan Fu, Qian Feng, Yu-Bin Ding","doi":"10.1093/biolre/ioag163","DOIUrl":"10.1093/biolre/ioag163","url":null,"abstract":"<p><p>Endometrial decidualization is essential for successful embryo implantation and pregnancy establishment. This study investigates the role of high mobility group box 1 (HMGB1) in endometrial stromal cells (hESCs) during decidualization. We found that HMGB1 expression was upregulated during decidualization in vitro and in normal decidual tissues but was reduced in decidua from patients with recurrent spontaneous abortion (RSA). HMGB1 Knockdown in hESCs impaired decidualization by disrupting stromal cell differentiation, reducing the expression of prolactin (PRL) and insulin like growth factor binding protein 1 (IGFBP1), and promoting aberrant cell proliferation. HMGB1 deficiency resulted in mitochondrial dysfunction, characterized by impaired oxidative phosphorylation, reduced ATP production, and altered mitochondrial morphology and membrane potential. Mechanistically, HMGB1 regulated the expression of PPARG coactivator 1 alpha (PPARGC1A), a key regulator of mitochondrial biogenesis and oxidative metabolism, suggesting that HMGB1 contributes to decidualization through PPARGC1A mediated metabolic regulation. Furthermore, reduced PPARGC1A expression in RSA decidua further supports the involvement of the HMGB1-PPARGC1A axis in decidual dysfunction. In addition, HMGB1 exhibited dynamic expression patterns in the uterus of early pregnant mice, with enriched expression in decidual regions at implantation sites. Collectively, these findings identify HMGB1 as an important regulator of decidualization by coordinating mitochondrial function and cellular energy metabolism, providing new insights into the molecular mechanisms underlying decidual dysfunction and pregnancy complications.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1268-1280"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629428","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":"Biochemical profile of the follicular environment in cattle following intrafollicular transfer of immature oocytes†.","authors":"Nayara Ribeiro Kussano, Otavio Faria, Laryssa Pimenta, José Felipe Warmling Sprícigo, Maurício Machaim Franco, Margot Alves Nunes Dode","doi":"10.1093/biolre/ioag164","DOIUrl":"10.1093/biolre/ioag164","url":null,"abstract":"<p><p>Intrafollicular transfer of immature oocytes (IFIOT) is a promising embryo production strategy, but outcomes remain poor and inconsistent. We investigated the effects of the injection procedure and the number of injected cumulus-oocyte complexes (COCs) on the biochemical and molecular environment of follicles. First, dominant follicles from hormonally synchronized heifers were either not injected (NIFIOT), injected with medium only (IFIOTM), or injected with medium containing COCs (IFIOT-COCs). Follicular fluid was analyzed for cell-free DNA (cfDNA), oxidative stress markers (glutathione peroxidase [GPx] activity and ferric reducing/antioxidant power), steroid hormones, and metabolomic profiles using ultra-performance liquid chromatography-high-resolution mass spectrometry. Injection procedure increased cfDNA levels and altered steroidogenesis, with higher progesterone levels, lower estradiol levels, and lower E2/P4 ratios in the injected follicles. Metabolomic analysis revealed alterations in amino acid and anti-inflammatory pathways, with enrichment of these pathways in non-injected compared with injected follicles. In addition, follicles were injected with 25 or 50 COCs (IFIOT25 and IFIOT50) to assess the impact of oocyte number on the follicular environment. IFIOT25 follicles showed higher GPx activity and estradiol concentrations compared to IFIOT50, whereas IFIOT50 follicles exhibited the downregulation of redox- and stress-related genes (SOD1, GPX4, NFE2L2, HSP70, and CASP3) and lower embryo yield compared to IFIOT25 (42 vs 52%, respectively). Metabolomic analysis indicated alterations in lipid and energy metabolism, with key metabolites (creatine, l-acetylcarnitine, dodecanoic acid, and panthenol) reduced in the IFIOT50 group, suggesting impaired metabolic homeostasis at higher oocyte density. Overall, both the injection process and oocyte number influenced follicular physiology, potentially affecting oocyte quality, highlighting the need to refine IFIOT protocols.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1299-1314"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629194","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":"Extracellular zinc acts as a dynamic extracellular regulator of fertilization in Xenopus laevis†.","authors":"Rachel E Bainbridge, Kayla M Komondor, Jennifer M Miller, Beatrice L Milnes, Olivia G Brado, Khaalis M T Harris, Paushaly Sau, Eirlys Barbara, Sarah Khanzada, Risha Musuku, Julia Schack, Anne E Carlson","doi":"10.1093/biolre/ioag161","DOIUrl":"10.1093/biolre/ioag161","url":null,"abstract":"<p><p>For most animals, fertilization of an egg by more than one sperm is embryonically lethal, and eggs therefore deploy multiple blocks to prevent additional sperm from entering an already fertilized egg. While Zn2+ release has emerged as a conserved feature of the slow block, its precise role in external fertilizers remains unclear. Here, we demonstrate that Xenopus laevis fertilization triggers a robust efflux of Zn2+ and that insemination of X. laevis eggs in physiologically relevant concentrations of Zn2+ potently and reversibly suppresses early development. Our findings are consistent with the hypothesis that extracellular Zn2+ inhibits fertilization through multiple mechanisms. Extracellular Zn2+ prevents the fertilization-evoked depolarization, also called the fast block to polyspermy, by acting upstream of the Ca2+-activated Cl- channel transmembrane protein 16A (TMEM16A). Zn2+ also directly reduces sperm fertilizing capacity, although eggs are significantly more sensitive than sperm. Furthermore, Zn2+ coordinates with the egg's extracellular matrix to stabilize the glycoprotein-rich jelly coat, rendering it resistant to reductive removal and suggesting a structural mechanism by which Zn2+ limits sperm entry. The inhibitory effects of Zn2+ are fully reversed by extracellular Zn2+ chelator (ZX1), reinforcing the conclusion that Zn2+ functions as a dynamic extracellular regulator rather than an intracellular messenger. Our findings establish Zn2+ as a multi-level signal that reinforces fertilization barriers by targeting both gametes and modifying the egg's extracellular environment.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1124-1133"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629271","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":"Role of α-adrenergic activation during the hemodynamic response to maternal hyperoxygenation in fetal sheep†.","authors":"Jordan A Minns, Jack R T Darby, Steven K S Cho, Brahmdeep S Saini, Stacey L Holman, Christopher K Macgowan, Mike Seed, Janna L Morrison","doi":"10.1093/biolre/ioag165","DOIUrl":"10.1093/biolre/ioag165","url":null,"abstract":"<p><p>Normal neurodevelopment relies on effective placental oxygen transfer and the specialized circulatory shunts that direct oxygen-rich blood to key fetal organs. The tone of these shunts, particularly the ductus venosus, is critical for routing oxygen and nutrient-rich blood towards the fetal brain. However, these shunts are sensitive to both oxygenation status and sympathetic innervation. Notably, fetal hypoxia increases shunting through the ductus venosus via enhanced hepatic sympathetic activation, a mechanism that redistributes oxygen rich blood toward vital organs. Thus, we hypothesized that hyperoxygenation may decrease shunting through the ductus venosus via hepatic sympathetic regulation but may be reversed if combined with an α-adrenergic agonist. Pregnant ewes (n = 8) underwent fetal catheterization surgery at 116-117 days gestation. At 120-124 days gestation, ewes were anaesthetized, and magnetic resonance imaging (MRI) scans were performed during normoxia, hyperoxia, and hyperoxia + phenylephrine infusion to measure blood flow and oxygenation within the major fetal vessels using phase-contrast and T2 oximetry MRI techniques, respectively. Hyperoxia had minimal effects on fetal hemodynamics. However, with the addition of phenylephrine, there was increased flow through the ductus venosus and ascending aorta but decreased flow toward the brain via the carotid arteries. Hyperoxia + phenylephrine increased overall fetal oxygen delivery but decreased cerebral oxygen delivery, despite no change in ductus venosus shunting (ductus venosus/umbilical vein flow ratio). There was no change in fetal or cerebral oxygen consumption. In conclusion, hyperoxia + phenylephrine reduced cerebral oxygenation, indicating that increased ductus venosus flow does not translate to improved cerebral oxygen delivery when carotid vascular resistance is elevated.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1281-1291"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148667926","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":"Unexpected variability of gametogenic pathways and interspecific chromosomal leakage in Pelophylax esculentus hybrids†.","authors":"Martyna Frątczak, Veronika Labajová, Eleonora Pustovalova, Zuzana Majtánová, Krzysztof Kolenda, Petr Papežík, Marie Doležálková-Kaštánková, Magdalena Chmielewska, Lukáš Choleva, Peter Mikulíček, Dmitrij Dedukh","doi":"10.1093/biolre/ioag171","DOIUrl":"10.1093/biolre/ioag171","url":null,"abstract":"<p><p>Hybridization is common among animals and plants, but often leads to sterility due to improper chromosome pairing. Some hybrids overcome sterility through modified gametogenesis, enabling clonal or hemiclonal reproduction. In water frog hybrids from the Pelophylax esculentus complex, hybridogenesis typically ensures hemiclonal reproduction. These hybrids inherit haploid chromosomal sets (n = 13) from both parental species, P. lessonae and P. ridibundus. During hybrid gametogenesis, one genome is eliminated while the other is clonally transmitted. We analyzed hybrid males and females from Central Europe, where hybrids coexist with P. lessonae and with both parental species, to assess gametogenic stability and whether the P. lessonae genome is consistently eliminated. Most hybrids followed canonical gametogenesis with premeiotic elimination of the P. lessonae genome and endoreplication of the P. ridibundus genome, yielding haploid P. ridibundus gametes. Nevertheless, gametogenesis was frequently altered in males but not in females. Some hybrid males had spermatocytes with 13 or 26 univalents, 26 bivalents, or tetravalents, indicating variability in genome elimination and endoreplication. Some males produced diploid or haploid spermatids with P. ridibundus and P. lessonae genomes. Comparative genome hybridization revealed that some males with altered gametogenesis carried unusual chromosomes with mixed R and L signals. Furthermore, rare triploid males showed substitutions of P. lessonae chromosomes to P. ridibundus chromosomes. Despite altered gametogenesis, they produced spermatocytes and haploid spermatids with P. lessonae chromosomes and two P. ridibundus chromosomes that escaped elimination. Overall, despite a generally consistent pattern of genome transmission, hybrid males exhibit frequent deviations from canonical hybridogenesis across populations.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1315-1330"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13669405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787939","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":"Exogenous pressure during in vitro follicle growth suppresses oocyte size expansion without impairing functional competence.","authors":"Tomohiro Kohama, Go Nagamatsu","doi":"10.1093/biolre/ioag226","DOIUrl":"https://doi.org/10.1093/biolre/ioag226","url":null,"abstract":"<p><p>Pressure stimuli, such as those arising from physical forces and hydrostatic pressure in vivo, are known to regulate cellular differentiation and growth. In the ovarian microenvironment, such cues are important regulators of folliculogenesis; however, their roles during in vitro follicle growth remain unclear. This study examined the effects of exogenous pressure on mouse preantral follicles cultured in a gas-pressurized system. Follicles were cultured under 0, 33, or 100 kPa for 8 days. Although exogenous pressure suppressed oocyte diameter expansion (0 kPa, 79.9 μm; 33 kPa, 74.7 μm; 100 kPa, 69.0 μm), the number of transzonal projection and the expression of Myo10 were comparable among groups, indicating that granulosa cell-oocyte communication was maintained. Following in vitro maturation and fertilization, oocytes from the 33 and 100 kPa groups showed comparable rates of maturation, fertilization, and blastocyst development to those of the 0 kPa group. Live offspring were successfully obtained in all groups. Further, the total RNA and expression levels of representative maternal transcripts in oocytes were comparable among groups. Additional analysis revealed that oocytes of similar diameters obtained after shorter culture periods under non-pressurized conditions showed significantly lower RNA content and developmental competence than those grown under exogenous pressure. These results indicate that oocyte diameter does not necessarily reflect cytoplasmic maturation and functional competence under exogenous pressurized conditions. Overall, our findings highlight the limitations of using oocyte diameter as an oocyte quality indicator and provide new insights into the role of pressure stimuli in folliculogenesis and in vitro follicle growth systems.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191320","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":"Multi-omics analyses link dysregulated immune hemostasis to decreased endometrial MMP protein in recurrent pregnancy loss†.","authors":"Ruifang Wang, Nan Ding, Fangxiang Mu, Wei Zhang, Fang Wang","doi":"10.1093/biolre/ioag146","DOIUrl":"10.1093/biolre/ioag146","url":null,"abstract":"<p><p>This study aims to explore the potential mechanisms contributing to recurrent pregnancy loss (RPL) and identify potential biomarkers. We analyzed endometrial samples from 39 RPL and 22 healthy controls using proteomics, identifying differentially expressed proteins (DEPs) with DEqMS and quantifying immune cell infiltration with CIBERSORT. We also examined a decidual scRNA-seq dataset (CRA002181) to identify macrophage marker genes, performed WGCNA to correlate macrophage infiltration with protein expression, and conducted functional enrichment analysis. Immunofluorescence staining was conducted to quantify the proportions of CD3+, CD8a+, CD68+, and CD206+ cells, and Western blot analysis was performed to determine MMP9 expression in endometrial tissues from RPL and controls. M2 macrophages and CD8+ T cells were enriched in the endometrium of RPL. Proteomic analysis of endometrial tissues from RPL identified 310 DEPs associated with immune response, cell adhesion, and secretory granule processes. From the scRNA-seq dataset, 295 macrophage marker genes were identified. WGCNA revealed that the brown module exhibited the highest correlation with macrophage infiltration. MMP9 emerged as the sole intersecting candidate, showing marked downregulation in RPL. Mendelian randomization analysis showed that genetically predicted higher circulating MMP9 levels decrease RPL risk (OR 0.75, 95% CI 0.57-0.98; P = 0.036). Additionally, RPL patients showed significantly higher proportions of CD3+CD8a+ cells (P < 0.05) and CD68+CD206+ cells (P = 0.265), and decreased MMP9 protein expression (P < 0.05), compared with controls. In conclusion, this study indicates that an imbalance in endometrial M2 macrophage and CD8+ T cell immune infiltration is associated with RPL. MMP9 may represent a potential predictive biomarker for RPL.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1226-1238"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444294","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 NPM1/p53 nucleolar stress signaling pathway promotes endometrial receptivity establishment in goats via the Wnt/β-catenin pathway†.","authors":"Yan Liu, Jingyi Yang, Deming Xu, Lingkang Liu, Xinyu Yu, Ben Liu, Chunhe Guo, Xue Yang, Qingcan Fan, Lucheng Zheng, Lizhi Li, Xiaoyue Wang, Wei Hu","doi":"10.1093/biolre/ioag158","DOIUrl":"10.1093/biolre/ioag158","url":null,"abstract":"<p><p>In goats, embryo implantation is superficial, making endometrial receptivity a key determinant of pregnancy success. Although the NPM1/p53 nucleolar stress pathway is involved in endometrial receptivity in mice and humans, its role in ruminants remains unknown. Using early-pregnancy goat models, in vitro-induced goat endometrial epithelial cells (gEECs), and low-dose Actinomycin D (ActD) to trigger nucleolar stress, we investigated this signaling axis in goat endometrial receptivity. Compared with pre-receptive Day 10 endometrium, receptive Day 16 endometrium showed increased NPM1 expression in epithelial cells, accompanied by its translocation from the nucleolus to the nucleoplasm. Markers of nucleolar stress (p53, Cyclin-Dependent Kinase Inhibitor 1A, MDM2) were upregulated, while precursor ribosomal RNA levels were reduced. In gEECs, low-dose ActD effectively activated the NPM1/p53 pathway, which was also activated during in vitro receptivity induction using estrogen, progesterone, and interferon-tau. Activation of this pathway by ActD increased receptivity markers [Homeobox A10 (HOXA10), Homeobox A11 (HOXA11), Msh homeobox 1], recapitulating changes seen during receptivity induction, whereas Npm1 knockdown attenuated this effect. ActD treatment also activated Wnt/β-catenin signaling. Pretreatment with the Wnt/β-catenin inhibitor Adavivint markedly reduced ActD-induced upregulation of HOXA10 and HOXA11 proteins but did not affect p53 expression. Together, these results indicate that the NPM1/p53 nucleolar stress pathway promotes endometrial receptivity in goats, at least in part, through the Wnt/β-catenin pathway. This work expands understanding of endometrial receptivity in ruminants and provides a basis for further investigation of nucleolar stress in reproductive regulation.</p>","PeriodicalId":8965,"journal":{"name":"Biology of Reproduction","volume":" ","pages":"1255-1267"},"PeriodicalIF":3.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577035","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}