{"title":"Formation of the hyaluronan-serum-derived hyaluronan-associated protein complex during cumulus expansion contributes to in vitro maturation of porcine oocytes.","authors":"Masaki Yokoo, Naoko Kimura","doi":"10.1071/RD26008","DOIUrl":"10.1071/RD26008","url":null,"abstract":"<p><strong>Context: </strong>Serum-derived hyaluronan-associated proteins (SHAPs), which are identical to the heavy chains of the inter-α-trypsin inhibitor (ITI) family of proteins, bind to hyaluronan produced by cumulus cells, thus forming the hyaluronan-SHAP complex, which stabilises the hyaluronan-rich matrix of cumulus-oocyte complexes (COCs) during cumulus expansion. However, the role of the hyaluronan-SHAP complex in inducing oocyte maturation is still poorly understood.</p><p><strong>Aims: </strong>Hence, this study was conducted to investigate the effects of hyaluronan retention within COCs on the formation of the hyaluronan-SHAP complex during cumulus expansion in porcine oocytes matured in vitro.</p><p><strong>Methods: </strong>Western blot analysis and enzyme-linked immunosorbent assays were performed to detect SHAPs in porcine follicular fluid (pFF) and to quantify hyaluronan respectively.</p><p><strong>Key results: </strong>The degree of cumulus expansion and oocyte maturation rates were proportional to the amount of hyaluronan retained within the COCs. SHAP was detected in pFF used for in vitro oocyte maturation and in the matrix of expanded COCs. Furthermore, immunodepletion of the ITI family proteins from pFF not only inhibited the formation of the hyaluronan-rich COC matrix, but also decreased oocyte maturation rates in a concentration-dependent manner.</p><p><strong>Conclusions: </strong>These results suggest that hyaluronan-SHAP complex formation during cumulus expansion may contribute to oocyte maturation.</p><p><strong>Implications: </strong>This finding is important for improving the culture system for porcine oocyte maturation in vitro.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 8","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ozlem Isigibol Gezgin, Mustafa Oguzhan Akbulut, Seyda Erdogan, Seref Erdogan
{"title":"Comparative analysis of acidosis defense mechanisms in preimplantation embryos in BALB/c strain mice: in vivo vs in vitro development.","authors":"Ozlem Isigibol Gezgin, Mustafa Oguzhan Akbulut, Seyda Erdogan, Seref Erdogan","doi":"10.1071/RD25154","DOIUrl":"10.1071/RD25154","url":null,"abstract":"<p><strong>Context: </strong>Intracellular pH (pHi) regulation is critical for all cell types, including preimplantation embryos. Embryos maintain pHi homeostasis through ion exchangers that respond to both acidic and alkaline challenges.</p><p><strong>Aims: </strong>While alkalosis defense mechanisms decline in later embryonic stages, this study investigated whether acidosis defense mechanisms - specifically Na+/H+ exchanger (NHE) activity alone and in conjunction with sodium-dependent chloride/bicarbonate exchanger (NDBCE) - remain active across developmental stages in in vivo- and in vitro-derived embryos.</p><p><strong>Methods: </strong>In vivo-derived embryos (from 2-cell to blastocyst stage) were collected from BALB/c strain female mice. To obtain embryos at the same stages under in vitro conditions, in vivo-derived pronuclear (PN) zygotes were incubated in potassium simplex optimized medium (KSOM) medium. All embryos were loaded with the pH-sensitive fluorophore BCECF-AM (2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester) and their recovery rates from induced acidosis were quantified microspectrofluorometrically in two different solutions (bicarbonate-free pHKFHM and pHKSOM). The contributions of NHE1 and NHE3 isoforms were assessed using specific inhibitors (cariporide and S3226). Additionally, indirect immunofluorescence was performed to visualize NHE and NDBCE proteins in a subset of embryos.</p><p><strong>Key results: </strong>The exchanger activities were high at the 2-cell stage of the embryos and there was no significant decrease across in vivo or in vitro developmental stages. Both NHE1 and NHE3 isoforms contributed to acidosis recovery.</p><p><strong>Conclusions: </strong>We found that both in vitro and in vivo embryos returned to resting pH at comparable rates in both solutions.</p><p><strong>Implications: </strong>The absence of functional differences between in vivo- and in vitro-cultured embryos implies that advanced-stage in vitro-derived embryos retain physiological competence, supporting their potential use in IVF applications.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 8","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148045370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanne M Smith, Patricio D Palacios, Pablo Andrés Segura Forero, Rhiannon J Gurkin, Tori Doyle, Gry Boe-Hansen, Andrés Gambini
{"title":"FGF2, LIF, and IGF1 supplementation during in vitro maturation or culture improves equine ICSI embryo development in an age-dependent manner.","authors":"Joanne M Smith, Patricio D Palacios, Pablo Andrés Segura Forero, Rhiannon J Gurkin, Tori Doyle, Gry Boe-Hansen, Andrés Gambini","doi":"10.1071/RD26023","DOIUrl":"10.1071/RD26023","url":null,"abstract":"<p><strong>Context: </strong>Ovum pickup (OPU) combined with intracytoplasmic sperm injection (ICSI) has reshaped equine assisted reproduction, enabling embryo production from mares and stallions with constrained breeding opportunities; however, limited efficiency of in vitro maturation (IVM) and in vitro culture (IVC) continues to hinder embryo production. Growth factor supplementation with fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF), and insulin-like growth factor 1 (IGF1) in combination (FLI) has been shown to enhance oocyte and embryo developmental competence in several species.</p><p><strong>Aims: </strong>This study evaluated whether FLI supplementation during IVM or IVC improves developmental outcomes of equine ICSI embryos and whether responses are influenced by donor mare age.</p><p><strong>Methods: </strong>Oocytes were assigned to IVM with or without FLI or cultured post-ICSI in IVC media with or without FLI. Developmental outcomes, including maturation, cleavage, blastocyst formation, blastocyst diameter, and pregnancy establishment, were assessed across defined donor-mare age categories.</p><p><strong>Key results: </strong>FLI supplementation did not affect overall maturation or cleavage rates. Blastocyst formation was significantly increased only in oocytes from middle-aged mares when FLI was added during either IVM or IVC. Supplementation during IVC also increased blastocyst diameter. Pregnancy establishment to Day 45 was marginally higher for embryos derived from FLI-treated oocytes, particularly following vitrification.</p><p><strong>Conclusions: </strong>These findings showed age-dependent responses to FLI, with the greatest benefit in middle-aged mares, supporting further molecular studies of its developmental effects.</p><p><strong>Implications: </strong>These results indicated that FLI supplementation can be incorporated into equine OPU-ICSI systems to improve clinical embryo production outcomes, particularly for middle-aged donor mares.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 7","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Your field needs your data! Raising the standard of quality control and data accessibility in reproductive proteomics.","authors":"David A Skerrett-Byrne","doi":"10.1071/RD26034","DOIUrl":"10.1071/RD26034","url":null,"abstract":"<p><p>The field needs your data. Despite rapid progress in reproductive proteomics, a major barrier to scientific advancement remains the limited availability and transparency of proteomic datasets. Although more than 2000 sperm proteomics studies are indexed on PubMed, fewer than 414 datasets have been deposited in ProteomeXchange, leaving the majority of published findings effectively inaccessible for reanalysis. This Viewpoint highlights the urgent need for improved data stewardship, standardised quality control and open access to raw mass spectrometry files across reproductive biology. In this article, I outline how transparent false discovery rate control, true biological replication and clearly defined quantitative thresholds are essential for generating robust and interpretable proteomic outputs. I further discuss how interactive data platforms, such as ShinyApps, can substantially improve the accessibility and usability of these complex reproductive proteomic datasets. Using recent examples, I demonstrate how public data reanalysis can uncover species-conserved pathways, improve proteome coverage, validate biological functions and enable new discoveries and insights far beyond the aims of the original studies. Finally, I present a practical roadmap for authors, reviewers and journals to ensure that reproductive proteomics embraces the FAIR data principles, and moves towards a culture where sharing raw data, comprehensive metadata and interactive applications becomes standard practice. To support implementation, a concise checklist is provided to summarise key criteria for data availability, quality control and metadata reporting. Improving data accessibility and quality will not only strengthen individual studies, but will accelerate discovery and create a more robust, connected and future-proof foundation for reproductive biology.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 7","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147725406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of YAP1 during oocyte maturation.","authors":"T Sun, F J Diaz","doi":"10.1071/RD24204","DOIUrl":"10.1071/RD24204","url":null,"abstract":"<p><strong>Context: </strong>Yes-associated protein 1 (YAP1) plays essential roles in somatic cell proliferation and differentiation and is regulated by cell cycle proteins and mechanical cues transduced by the actin cytoskeleton. YAP1 has been localized to the mitotic spindle. Whether YAP1 may participate in oocyte maturation is not known.</p><p><strong>Aims: </strong>Determine effect of YAP inhibitor on oocyte maturation and the potential involvement of cell cycle regulators and actin polymerization modulators on YAP localization and phosphorylation status during oocyte maturation.</p><p><strong>Methods: </strong>Mouse oocytes were cultured in vitro alone or in the presence of various small molecule inhibitors blocking YAP1, cyclin dependent kinase 1 (CDK1), phosphatase protein 2 A (PP2A), actin polymerization and the resulting effects on maturation, YAP localization by immunocytochemistry and/or YAP phosphorylation by western blot were determined.</p><p><strong>Key results: </strong>Blocking YAP1 activity with verteporfin hampers oocyte maturation, arresting the majority of oocytes at metaphase I (MI), with a distorted spindle structure. Moreover, YAP1 localized to the meiotic spindle and is phosphorylated on T119 beginning at metaphase I, which is regulated in part by PP2A phosphatase but is not strongly affected by CDK1 inhibitors (RO-3306). The increase in YAP1 phosphorylated on T119 (pYAP1) at MI mirrors the rise in CDK1 activity, suggesting an association between CDK1, pYAP1-T119 and PP2A.</p><p><strong>Conclusions: </strong>The results link pYAP1-T119 with cell cycle regulators CDK1, PP2A, and the meiotic spindle, but not with changes in actin polymerization. These findings suggest a previously unknown role of YAP1 in regulating meiotic spindle shape during oocyte maturation.</p><p><strong>Implications: </strong>Modulation of YAP1 activity during oocyte maturation may allow for better in vitro maturation procedures to be developed.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 7","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrative analysis of follicular fluid metabolites, exosomal miRNAs and granulosa cell mRNAs shows their interplay in women of advanced maternal age.","authors":"Zhengda Li, Shikai Wang, Xianbao Mao, Xiaohui Zhang, Pingpin Wei, Liangshi Chen, Liling Liu, Lintao Xue, Ziyun Ruan","doi":"10.1071/RD25173","DOIUrl":"10.1071/RD25173","url":null,"abstract":"<p><strong>Context: </strong>Advanced maternal age (especially over 40 years) shows markedly declined fertility, although the exact mechanisms remain unclear. Exosomal microRNAs (miRNAs) within follicular fluid (FF) regulate granulosa cell (GC) functions, thereby inducing alterations in the metabolic features of the FF. However, the specific dysregulation and functional impact of this exosomal miRNA-GC axis in the context of ovarian aging require further elucidation.</p><p><strong>Aims: </strong>To delineate the distinct expression profiles of FF exosomal miRNAs and GC mRNAs, coupled with FF metabolic features, in women of advanced maternal age, and to explore the integrated regulatory networks linking these components.</p><p><strong>Methods: </strong>FF samples were collected from the aged group (≥40 years, n = 19) and young group (≤30 years, n = 19). Centrifugation separated it into GCs, exosomes, and the remaining FF containing metabolites. Each fraction was analyzed for differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differential metabolites (DMs).</p><p><strong>Key results: </strong>Analysis identified 373 DEmRNAs, 50 exosomal DEmiRNAs (targeting 2633 genes), and 97 DMs. Integrated correlation analysis pinpointed a core regulatory axis, hsa-miR-132-3p_CHAC1, which was strongly associated with four key metabolites (7-HOCA, Lysopc(18:1), 9(S)-Hpode, Androsterone Sulfate). This axis potentially disrupts cellular redox homeostasis.</p><p><strong>Conclusions: </strong>Multiomics analysis uncovered a dysregulated FF exosomal miRNA_GC mRNA_metabolite network in women of advanced maternal age compared with the young group, with the hsa-miR-132-3p_CHAC1 axis potentially mediating age-related ovarian dysfunction via perturbed cellular redox homeostasis.</p><p><strong>Implications: </strong>This study offers insights into the mechanisms underlying the age-related decline in female fertility.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 7","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weilan Liu, Wenxin Shi, Jiahua Zheng, Yanfang Du, Yan Jiang, Caifu Zhao, Zhiqiang Zhang, Li Feng, Xianghua Huang
{"title":"Paeonol alleviates intrauterine adhesion by suppressing endometrial stromal cell activation via AKT1, based on network pharmacology.","authors":"Weilan Liu, Wenxin Shi, Jiahua Zheng, Yanfang Du, Yan Jiang, Caifu Zhao, Zhiqiang Zhang, Li Feng, Xianghua Huang","doi":"10.1071/RD25246","DOIUrl":"10.1071/RD25246","url":null,"abstract":"<p><strong>Context: </strong>Intrauterine adhesion (IUA) causes secondary infertility and recurrent miscarriage, yet therapeutic options remain limited. Paeonol is widely used for gynecological diseases, but its precise role in IUA therapy is unclear.</p><p><strong>Aims: </strong>This study aims to explore the molecular mechanism of paeonol in IUA.</p><p><strong>Methods: </strong>Network pharmacology identified paeonol's potential targets and core proteins via a protein-protein interaction network. Bioinformatic pathway enrichment analyses and molecular docking elucidated mechanisms and validated binding. The optimal concentration and treatment time of paeonol were screened using Cell Counting Kit-8 (CCK-8) assays. In a transforming growth factor (TGF)-β-induced activated primary endometrial stromal cell (ESC) model, paeonol's effects on proliferation and migration were evaluated using CCK-8, wound healing, and Transwell assays. Expression levels of AKT1 and collagen synthesis-related markers were assessed by Western blotting. Protein levels of type I collagen and vimentin were assessed by immunofluorescence staining. In a IUA rat model, the in vivo efficacy of paeonol in alleviating IUA via AKT1 regulation was validated based on pathological, inflammatory, and reproductive parameters.</p><p><strong>Key results: </strong>Paeonol targets were significantly enriched in the phosphoinositide 3-kinaseK-AKT pathway. In vitro, paeonol blocked TGF-β-induced activation of primary ESC, reducing cell viability and migration. Mechanistically, paeonol antagonised TGF-β-induced ESC activation by suppressing AKT1, thereby attenuating IUA. In vivo, paeonol alleviated pathological changes of endometrial tissues, reduced fibrosis, and suppressed inflammation in IUA rats.</p><p><strong>Conclusion: </strong>Paeonol blocks AKT1 activation to suppress inflammation and fibrosis, ultimately slowing IUA progression.</p><p><strong>Implications: </strong>This study provides a new theoretical basis for paeonol use in IUA therapy.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 7","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisandra L Martin, Kerry V Fanson, Stephen D Johnston, Phoebe J Lewis, Sarah J Meachem, Paul D O'Leary, Marissa L Parrott, Andrew J Pask, Alexandra Pavlova, Nadine M Richings, Nicola Rivers, Joanna Sumner, Peter Temple-Smith, Christopher W Tubbs, Bob B M Wong, Raymond J Rodgers
{"title":"Harnessing reproductive biology to conserve wildlife species.","authors":"Lisandra L Martin, Kerry V Fanson, Stephen D Johnston, Phoebe J Lewis, Sarah J Meachem, Paul D O'Leary, Marissa L Parrott, Andrew J Pask, Alexandra Pavlova, Nadine M Richings, Nicola Rivers, Joanna Sumner, Peter Temple-Smith, Christopher W Tubbs, Bob B M Wong, Raymond J Rodgers","doi":"10.1071/RD26022","DOIUrl":"10.1071/RD26022","url":null,"abstract":"<p><p>Habitat destruction, changing climate and other anthropogenic impacts have resulted in the recorded extinctions of hundreds of species, with many more undocumented extinctions being likely to have occurred. Approaches to conserving threatened species include protection or improvement of habitat, fenced conservation reserves, species translocations and reintroductions, elimination of environmental toxins, breeding programs in reserves or captivity, and genetic rescue and management. The latter includes storage of gametes, stem cells or embryos, to both conserve species and maintain or expand their genetic diversity. Many of these approaches require a basic knowledge of the reproductive biology of the species of interest. Such knowledge is difficult to achieve because of the astonishing diversity of species-specific reproductive strategies that have evolved. Unfortunately, for many species we simply do not have that knowledge. This report summarises key discussions from a workshop titled Reproductive Biology Research Needed for Saving our Wildlife held in Melbourne, Australia, and attended by stakeholders from zoos, wildlife organisations, universities, museums and government organisations. The workshop prioritised aspects of reproductive biology knowledge needed, how this knowledge might be obtained, and how it should be deployed. Using examples of planned and successful conservation strategies for individual species, the workshop participants considered environmental challenges, managing introduced species, captive breeding programs, challenges for assisted reproductive technologies, de-extinction science in conservation efforts, examination of reproductive steroid hormones across species, endocrine disruption, and cryopreservation of genomic diversity to assist the management of wild and captive populations. The workshop highlighted the magnitude of the issues involved and identified reproductive approaches to be used to direct future conservation efforts for saving threatened species.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147597372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synergistic effect of glutathione and metformin mitigates testicular apoptosis by ameliorating gonadotropin hormones and gene expression in streptozotocin-induced diabetic male mice.","authors":"Razia Sardar, Fathiah Abdullah, Yuhaniza Shafinie Kamsani, Nor-Ashikin Mohamed Noor Khan","doi":"10.1071/RD25089","DOIUrl":"10.1071/RD25089","url":null,"abstract":"<p><strong>Context: </strong>Diabetes mellitus (DM) is a metabolic disorder that impairs the body's ability to regulate blood sugar levels, leading to cellular damage and apoptosis. Metformin (Met) and glutathione (GSH) are key antioxidants that prevent damage to mitochondrial DNA and proteins by modulating oxidative stress in testicular cells.</p><p><strong>Aims: </strong>This study assessed concomitant therapy with GSH and Met to mitigate testicular apoptosis in diabetic male mice.</p><p><strong>Methods: </strong>Six- to eight-week-old male BALB/c mice were randomly divided into four groups (n = 6): DM control, DM + Met (200 mg/kg), DM + GSH (15 mg/kg), and DM + Met (200 mg/kg) + GSH (15 mg/kg). Diabetes was induced by i.p. injection of 50 mg/kg body weight (BW) streptozotocin for five consecutive days. The DM control group served as a baseline to evaluate the effects of treatments. GSH was administered weekly (i.p.), and Met was administered orally daily for 35 consecutive days.</p><p><strong>Key results: </strong>BW and fasting blood glucose levels were monitored on Day 0 and Day 44. The fasting blood glucose levels were reduced (P < 0.05, P < 0.01, P < 0.001) while BW, the number of Bax-positive cells, Bax mRNA expression, and Bax : Bcl-2 ratio were restored in all treatment groups (P < 0.05, P < 0.01, P < 0.001). In contrast, FSH, LH, testosterone, the number of Bcl-2 positive cells, Bcl-2 mRNA expression, and mitochondrial genes were increased in all treatment groups (P < 0.05, P < 0.01, P < 0.001).</p><p><strong>Conclusion: </strong>These findings suggest that GSH combined with Met restores apoptotic and mitochondrial dynamics, potentially mitigating diabetes-associated testicular damage by modulating the expression of genes involved in apoptotic and mitochondrial processes, thus positioning GSH as a promising complementary therapy.</p><p><strong>Implications: </strong>Combined GSH and Met therapy may offer a novel synergistic strategy to protect male fertility in diabetes condition by targeting cellular stress pathways. Further studies are warranted to translate these findings into clinical applications.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Margarete Meyerholz-Wohllebe, Anna Maria Kneidl, Simone Tamara Knoch, Sandra Haug, Frank Weber, Yury Zablotski, Christoph Gabler, Wolfram Petzl, Holm Zerbe
{"title":"IL10 is a potent modulator of IL1-mediated inflammation in bovine endometrial explants.","authors":"Marie Margarete Meyerholz-Wohllebe, Anna Maria Kneidl, Simone Tamara Knoch, Sandra Haug, Frank Weber, Yury Zablotski, Christoph Gabler, Wolfram Petzl, Holm Zerbe","doi":"10.1071/RD26013","DOIUrl":"10.1071/RD26013","url":null,"abstract":"<p><strong>Context: </strong>Bovine uterine inflammation impairs fertility, animal welfare and economics. Balanced regulation of interleukin-1 family proteins is crucial to resolve endometrial inflammation.</p><p><strong>Aim: </strong>mRNA expression of interleukin 1B (IL1B) and its receptor antagonist (IL1RA) was examined in bovine endometrial explants.</p><p><strong>Methods: </strong>Endometrial explants from 26 cows were incubated with heat-inactivated pathogenic Escherichia coli, opportunistic Bacillus pumilus or commensal and potentially protective Lactobacillus buchneri (3, 14 and 24 h) and with cytokines (24 h; IL1B, IL17A, IL10). mRNA expression of IL1B and IL1RA was quantified via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and mixed effects models were used for statistical analysis.</p><p><strong>Key results: </strong>IL1B mRNA expression increased after bacterial challenge at all timepoints (P < 0.001). IL1RA mRNA expression increased after Escherichia coli and Bacillus pumilus exposure only at 3 h, but after Lactobacillus buchneri at 14 and 24 h (P < 0.010). A pro-inflammatory shift of the IL1RA:IL1B ratio was detected at all timepoints and for all bacterial challenges (P < 0.020). Stimulation with IL10 reduced IL1B and IL1RA mRNA expression and shifted the IL1RA:IL1B ratio in an anti-inflammatory direction (P < 0.001).</p><p><strong>Conclusion: </strong>This study confirmed explant culture as a suitable model for analyzing inflammatory regulation in the bovine endometrium and identified IL10 as a potent modulator of endometrial IL1B and IL1RA.</p><p><strong>Implications: </strong>Not only Escherichia coli and Bacillus pumilus, but also unexpectedly Lactobacillus buchneri, induced initial pro-inflammatory mRNA expression patterns to be different depending on culture duration. This highlights the need for further research on pathogenic and opportunistic versus potentially protective bacteria in bovine uterine health.</p>","PeriodicalId":516117,"journal":{"name":"Reproduction, fertility, and development","volume":"38 6","pages":""},"PeriodicalIF":2.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}