Molecular and Cellular Endocrinology最新文献

{"title":"Endometrial cells and extracellular vesicles response to high body energy reserves in bovine: Insights into miRNA and mRNA regulation before embryo arrival","authors":"Schaienni Fontoura Saldanha ,&nbsp;Natália Marins Bastos ,&nbsp;Juliana Germano Ferst ,&nbsp;Rodrigo Silva Goulart ,&nbsp;Ricardo Perecin Nociti ,&nbsp;Marcos Roberto Chiaratti ,&nbsp;Angélica Camargo dos Santos ,&nbsp;Flávio Vieira Meirelles ,&nbsp;Felipe Perecin ,&nbsp;Juliano Coelho da Silveira","doi":"10.1016/j.mce.2025.112665","DOIUrl":"10.1016/j.mce.2025.112665","url":null,"abstract":"<div><div>Body energy reserves influence reproductive performance in cattle. Previous findings from our laboratory showed that cows with high body energy reserves (HBER) have lower ovulation and embryo recovery rates compared to cows with moderate reserves (MBER). To investigate whether these reproductive differences are associated with changes in the uterine environment, Nelore cows from the same herd were assigned to MBER or HBER groups through nutritional management. Following estrous synchronization and artificial insemination, animals were slaughtered ∼120 h after ovulation induction. Samples from the uterotubal junction (UTJ) and anterior uterine horn (ANT) were collected. Extracellular vesicles (EVs) were isolated from uterine fluid by flushing, and endometrial tissue was sampled for molecular analysis. Nanoparticle tracking analysis revealed no differences in EV concentration or size between groups. However, when comparing MBER and HBER groups, miRNA profiling identified 8 and 9 differentially expressed miRNAs between MBER and HBER in EVs from the UTJ and ANT, respectively, and 2 differentially expressed miRNAs in endometrial cells from the UTJ, suggesting potential differences in molecular profiles. Transcriptomic analysis of endometrial cells revealed 430 and 35 differentially expressed genes (DEGs) in the UTJ and ANT, respectively, between MBER and HBER groups. The higher number of DEGs in the UTJ may suggest a greater molecular response, which is reflected by more extensive pathway enrichment compared to the ANT. miRNA–mRNA integration, performed by intersecting predicted miRNA targets with the differentially expressed mRNAs from our RNA-seq data, suggests that differentially expressed genes may be regulated by miRNAs altered between groups, indicating miRNA-mediated effects of metabolic condition on the uterine transcriptome. These findings suggest that high body energy reserves are associated with enrichment of immune and metabolism related pathways in the uterine environment, especially in the UTJ, which may reflect a pro-inflammatory, metabolically altered state potentially impairing early embryo development and maternal-embryonic communication.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"610 ","pages":"Article 112665"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of novel amino acid substituted and acylated spexin analogues on pancreatic beta-cell function, appetite and glucose homeostasis","authors":"Daniel M. Gallagher ,&nbsp;Md Zahidul Islam Khan ,&nbsp;Steven Patterson ,&nbsp;Finbarr P.M. O'Harte ,&nbsp;Nigel Irwin","doi":"10.1016/j.mce.2025.112657","DOIUrl":"10.1016/j.mce.2025.112657","url":null,"abstract":"<div><h3>Objective</h3><div>The neuropeptide spexin is recognised as a satiety-inducing hormone, but overall effects on metabolism are less characterised. Rapid enzymatic metabolism means elucidating biological effects of spexin is challenging, because the bioactive profile is short.</div></div><div><h3>Methods</h3><div>Therefore, in the present study, an Asp¹ for Asn¹ substituted spexin analogue, D¹Spx, alongside two related fatty acid derivatised analogues, (γGlu-Pal)-D¹Spx and (K¹¹γGlu-Pal)-D¹Spx, were synthesised and effects on pancreatic beta-cell secretory function and health investigated together with impact on appetite and glucose homeostasis in mice.</div></div><div><h3>Results</h3><div>Spexin immunoreactivity was initially confirmed in BRIN-BD11 beta-cells. Interestingly, like native spexin, D¹Spx was liable to plasma enzyme degradation, but the fatty acid derivatised molecules remained intact. None of the peptides augmented insulin secretion from BRIN-BD11 cells. Moreover, the spexin peptides inhibited alanine‐induced insulin secretion, with native spexin having no effect on intracellular calcium. However, all spexin peptides (10⁻⁸ and 10⁻⁶ M) promoted beta-cell proliferation, whilst native spexin and (γGlu-Pal)-D¹Spx protected against cytokine-induced beta-cell apoptosis. When administered intraperitoneally to mice, spexin peptides lacked effects on appetite regulation, even at elevated doses of 250 nmol/kg. Following conjoint injection with saline, none of the spexin peptides affected blood glucose levels barring a negligible increase by D¹Spx. When administered together with glucose, (γGlu-Pal)-D¹Spx slightly increased blood glucose at 30 min post-injection, but there was no overall difference between the spexin peptides when compared to glucose alone.</div></div><div><h3>Conclusions</h3><div>Acylation creates stable spexin analogues with similar bioactivity as native spexin, including promotion of beta-cell proliferation and partial protection against apoptosis.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112657"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation of sex: the role of DNA methylation and zbtb38 in zebrafish sex differentiation and heat-induced masculinization","authors":"Fabien Pierron,&nbsp;Débora Heroin,&nbsp;Flore Daramy","doi":"10.1016/j.mce.2025.112636","DOIUrl":"10.1016/j.mce.2025.112636","url":null,"abstract":"<div><div>There is increasing evidence that global change can threaten biodiversity by inducing skewed sex ratios. Accumulating evidences support a role of epigenetics, mainly DNA methylation, in sex differentiation. The aim of the present work was to investigate the potential role of <em>zbtb38,</em> a transcriptional factor that binds to methylated promoters, in sex differentiation and/or maintenance in zebrafish. We analyzed the methylation and transcription level of <em>zbtb38</em> in males, females and undifferentiated individuals raised at standard or high temperature, a masculinizing factor. Results were compared to those obtained for genes already known to be involved in sex differentiation/maintenance (<em>cyp19a1a</em>, <em>foxl2a</em>, <em>dmrt1</em>). All genes presented a sex-specific pattern of DNA methylation and transcription but the most significant differences between sexes were observed for <em>zbtb38</em>. Moreover, a highly significant positive correlation was observed between the methylation level of <em>zbtb38</em> and <em>cyp19a1a</em>, which encodes an enzyme that converts androgens into estradiol. However, while the hypermethylation of <em>cyp19a1a</em> was associated with its down-regulation, an inverse relationship was observed for <em>zbtb38</em>, providing a basis for mutual antagonism. Furthermore, <em>zbtb38</em> was the only gene for which its transcription level was affected by temperature, being up-regulated in females that escaped to masculinization. Finally, despite embryos presented a paternal methylome, <em>zbtb38</em> was the only gene for which its methylation level rapidly changed during early development to reach intermediate values between males and females at the larval stage, ie a bi-potential state. Our results strongly support a strategic role of DNA methylation and <em>zbtb38</em> in sex differentiation and maintenance.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112636"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ox-LDL-stimulated macrophage-derived exosomes regulate adipose tissue remodeling and promote the progression of atherosclerosis","authors":"Xiaoyu Liu ,&nbsp;Guoyan Xu ,&nbsp;Yunlu Xu ,&nbsp;Yuling Xu","doi":"10.1016/j.mce.2025.112660","DOIUrl":"10.1016/j.mce.2025.112660","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerosis (AS) is a chronic vascular disease, and perivascular adipose tissue dysfunction is an important cause of the arterial plaque formation involved. However, the underlying mechanism has not been fully elucidated. The aim of this study was to investigate the mechanism of oxidized low-density lipoprotein (ox-LDL) stimulation of macrophage-derived exosomes in the development of AS.</div></div><div><h3>Methods</h3><div>We isolated exosomes from ox-LDL-treated macrophages and injected them into Western diet-fed ApoE^−/− mice. We assessed AS, lipid metabolism, and endothelial function by histology, ELISA, qPCR, and western blotting, and examined BMP7 and OPA1 regulation in brown fat and vascular endothelium.</div></div><div><h3>Results</h3><div>Macrophage-derived exosomes were extracted, and their size was determined by transmission electron microscopy. Additionally, CD9, CD63, and TSG101 protein expression within these macrophages was determined. Compared with the control group, the exosomes group showed increased expression of AP2 and PPAR and decreased expression of UCP-1, PGC-1α, and BMP7. Furthermore, when BMP7 was knocked down, the expression of the lipid metabolites FASN, SCD1, HSL, and ATGL as well as of OPA1 decreased. In an ApoE^−/− mouse model, compared to the control group, increased arterial plaques and plaque lesion formation were observed in the exosome group, along with elevated expression of the lipid metrics TC, TG, LDL-C, and HDL-C and significant increases in the expression of the proinflammatory factors VCAM1, ICAM1, MCP-1, and IL-6. Consequently the progression of AS was aggravated in this group.</div></div><div><h3>Conclusions</h3><div>This study demonstrated that ox-LDL stimulated exosome secretion from macrophages, accelerating the AS process. It also showed that, mechanistically, BMP7 regulates the expression of OPA1 and affects the normal lipid metabolism, thereby accelerating AS.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112660"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α-Linolenic acid rich-chia seed improves glucose tolerance, modulates gluconeogenic pathway and hepatic insulin signaling in an experimental model of metabolic syndrome","authors":"Michelle Berenice Vega Joubert ,&nbsp;María Eugenia Oliva ,&nbsp;Paola Ingaramo ,&nbsp;María Eugenia D'Alessandro","doi":"10.1016/j.mce.2025.112643","DOIUrl":"10.1016/j.mce.2025.112643","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is recognized as the hepatic manifestation of Metabolic Syndrome. The aim of this work was to evaluate the effects of chia seed, rich in α-linolenic acid, on glucose tolerance, enzyme activities and transcription factors involved in gluconeogenesis, and key molecules in insulin signaling in sucrose-rich diet (SRD) fed rats. Male Wistar rats were fed a reference diet (RD) for 6 months or a SRD for 3 months. Then, the latter group was randomly divided into two subgroups. One subgroup continued receiving SRD for up to 6 months and the other was fed with a SRD where chia seed was incorporated as a source of dietary fat for the next 3 months (SRD + CHIA). The results showed that chia seed improved glucose tolerance, reversed the increase in PEPCK, FBPase, and Glucose-6-Pase, and reduced the Glucose-6-Pase/GK ratio. Additionally, chia seed improved tAMPK and pAMPK protein levels, while maintaining GLUT-2 protein levels similar to those in the RD group. Under insulin stimulation, p-AKT protein levels were higher in the SRD + CHIA group than in the unstimulated group. IRS-1 and PGC-1α protein expression levels were similar among the three experimental groups. Liver FOXO-1 mRNA expression was decreased in the SRD + CHIA group. Finally, chia seed increased the n-3/n-6 ratio in hepatic membrane phospholipids. The present study demonstrated that chia seed modulate multiple mechanisms that enhance glucose metabolism and insulin signaling in SRD fed rats. These effects are mediated, at least in part, by the enrichment of n-3 PUFAs in liver tissue.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112643"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental programming: Differing impact of prenatal testosterone and prenatal bisphenol-A -treatment on hepatic methylome in female sheep","authors":"John Dou ,&nbsp;Soundara Viveka Thangaraj ,&nbsp;Yiran Zhou ,&nbsp;Vasantha Padmanabhan ,&nbsp;Kelly Bakulski","doi":"10.1016/j.mce.2025.112655","DOIUrl":"10.1016/j.mce.2025.112655","url":null,"abstract":"<div><div>Steroid hormones are integral to pregnancy and fetal development, regulating processes such as metabolism, inflammation, and immune responses. Excessive prenatal steroid exposure, through lifestyle choices or environmental chemicals, can lead to metabolic dysfunctions in offspring. The research focuses on how exposure to testosterone (T) and bisphenol A (BPA) affects the liver's DNA methylome, a key component of the epigenome influencing long-term health. Using Suffolk sheep, the study involved two cohorts: one exposed to prenatal-T and the other to prenatal-BPA. Whole genome bisulfite sequencing was employed to map DNA methylation across over 22 million CpG sites. Regions with p-value&lt;10⁻⁴ and a magnitude of difference of at least 5 % methylation between groups were considered differentially methylated. Results demonstrated substantial differential methylation in the liver tissues due to both treatments, with prenatal-T causing unique epigenetic modifications distinct from those induced by prenatal-BPA. Specifically, prenatal-T treatment resulted in 53 differentially methylated regions (DMRs), of which 31 were located in gene regions, including exons. Prenatal-BPA exposure led to 32 DMRs, with 22 associated with gene regions. These modifications were associated with genes governing lipid and glucose metabolism, potentially underlying the observed metabolic disruptions such as insulin resistance and dyslipidemia. Pathway analysis revealed that genes differentially methylated due to prenatal-T were involved in cellular organization, while those affected by prenatal-BPA were enriched in signal regulation pathways. The findings underscore how prenatal exposure to steroid excess and steroid-mimics influence epigenetic landscapes, contributing to metabolic disease programming.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112655"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic modifications in maternal pancreatic islets during the period around weaning in mice","authors":"Xadeni Burgos-Gamez ,&nbsp;Paulina Morales-Castillo ,&nbsp;Alain Hernández-Vázquez ,&nbsp;Karina Pastén-Hidalgo ,&nbsp;Francisco García-Vázquez ,&nbsp;Cristina Fernandez-Mejia","doi":"10.1016/j.mce.2025.112642","DOIUrl":"10.1016/j.mce.2025.112642","url":null,"abstract":"<div><div>Identifying the mechanisms and molecular factors that enhance beta-cell mass is crucial for developing strategies to combat diabetes, as beta-cell mass declines with disease progression. Recent research has indicated an increase in beta-cell proliferation and a significant islet expansion around the weaning period in mice. This study aims to identify transcripts associated with changes in the islets around weaning—a physiological stage previously unexplored in islets. A ribonucleic acid (RNA) sequencing analysis of the transcriptome was performed at four key time points: the end of lactation, when beta-cell proliferation increases; the day of weaning, when the hormonal and metabolic environment transitions from lactation to the non-lactating stage; the third day post-weaning, when islet area peaks, as observed in our prior studies; and in age-matched female control mice. The results revealed dynamic transcriptomic changes. The messenger ribonucleic acid (mRNA) expression levels of genes regulated by prolactin, including its receptor, signaling inhibitor <em>Cish</em>, tryptophan hydroxylase, and osteoprotegerin, increased during lactation and subsequently declined. Plasma prolactin concentrations rose during lactation, but plasma osteoprotegerin levels remained stable across groups. Notably, no changes were observed in known prolactin-regulated cyclins that positively influence the cell cycle, such as <em>Ccna2</em>, <em>Ccnb1</em>, and <em>Ccnb2</em>. However, a decrease in the expression of <em>Cdkn1a</em>, a negative regulator of the cell cycle, was noted. Surprisingly, microscopy analysis indicated increased apoptosis markers in islet peripheral cells that were negative for insulin immunostaining. This study is the first to identify transcriptomic and cellular changes around weaning, offering new insights into islet mass plasticity.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112642"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MeCP2 attenuates inflammation and regulates T cell phenotype via SFRP4 suppression in preeclampsia","authors":"Mei Peng ,&nbsp;Yanting Nie ,&nbsp;Ying Luo,&nbsp;Grace Divine Milebe Nkoua,&nbsp;Shaohan Zhang,&nbsp;Hongyu Liu,&nbsp;Wen Zhang,&nbsp;Songyuan Xiao,&nbsp;Yang Zhou,&nbsp;Weisi Lai,&nbsp;Yali Deng,&nbsp;Ling Yu,&nbsp;Jinyu Liu,&nbsp;Xihong Zhou,&nbsp;Yiling Ding","doi":"10.1016/j.mce.2025.112637","DOIUrl":"10.1016/j.mce.2025.112637","url":null,"abstract":"<div><div>Preeclampsia (PE) is a major pregnancy complication characterized by an aberrant immune response. Methyl CpG binding protein 2 (MeCP2) is a potential regulator of secreted frizzled-related protein 4 (SFRP4), and both MeCP2 and SFRP4 are implicated in immune homeostasis. This study investigated the regulatory role of MeCP2/SFRP4 in immune cells in PE. A rat model of PE induced by reduced uterine perfusion pressure (RUPP) and an <em>in vitro</em> model using lipopolysaccharide (LPS)-stimulated HTR-8/SVneo cells were established. A co-culture system of LPS-challenged HTR-8/SVneo cells and T cells was also employed. MeCP2 expression was reduced and inversely correlated with SFRP4 levels in PE. MeCP2 overexpression suppressed Th1/Th17 differentiation while promoting Th2/Treg phenotypes, along with modulation of associated immune cytokines. It also enhanced colony formation, proliferation, migration, and invasion, while reducing apoptosis following co-culture. SFRP4 supplementation reversed the effects of MeCP2 overexpression on T cell proliferation and cytokine release. Collectively, these findings suggest that MeCP2 regulates T cell phenotype and inflammatory responses by inhibiting SFRP4, providing potential avenues for immunotherapeutic intervention in PE.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112637"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose tissue-specific Yap knockout exacerbates diet-induced obesity through suppression of lipolysis","authors":"Huabing Xiao ,&nbsp;Ping Jiang ,&nbsp;Fan Xia ,&nbsp;Dayu Wu ,&nbsp;Hui Huang ,&nbsp;Sihui Tu ,&nbsp;Huilan Luo ,&nbsp;Yiling Wu ,&nbsp;Qiong Duan ,&nbsp;Lingyan Zhu","doi":"10.1016/j.mce.2025.112631","DOIUrl":"10.1016/j.mce.2025.112631","url":null,"abstract":"<div><h3>Background and aims</h3><div>YAP regulates various cellular processes, including cell contact inhibition, mechanotransduction, cell differentiation and proliferation, apoptosis, and cancer progression. Although YAP suppresses adipogenesis <em>in vitro</em>, its role in obesity has not yet been completely elucidated.</div></div><div><h3>Methods and results</h3><div>In this study, we generated an adipose tissue-specific <em>Yap</em> knockout mouse model (<em>Yap</em>aKO), and found that male, but not female, <em>Yap</em>aKO mice showed an enhanced high-fat diet-induced obesity phenotype compared to control mice. Mechanistically, this effect is potentially due to suppressed lipolytic activity, which results from the decreased expression of triglyceride lipolytic enzymes, including ATGL and HSL. The inhibition of lipolytic activity led to reduced levels of circulating free fatty acids during fasting, making male mice unable to maintain core body temperature after cold exposure and showing impaired exercise capability in the fasted state. This study reveals a novel role of YAP in controlling lipolysis.</div></div><div><h3>Conclusion</h3><div>YAP is a physiological regulator of lipolysis in the adipose tissue. YAP activation in adipose tissue may facilitate lipolysis and reduce obesity.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112631"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oocyte-specific Ahr deletion disrupts folliculogenesis and female fertility in mice","authors":"Pengtao Chen ,&nbsp;Jinpeng Ruan ,&nbsp;Fanzheng Xue ,&nbsp;Xuejuan Dai ,&nbsp;Chen Tang ,&nbsp;Mingyue Chen ,&nbsp;Nengming Xiao ,&nbsp;Zhijian Cai ,&nbsp;Chunyan Yang ,&nbsp;Chengyong He ,&nbsp;Wei Wang ,&nbsp;Zhenghong Zuo","doi":"10.1016/j.mce.2025.112656","DOIUrl":"10.1016/j.mce.2025.112656","url":null,"abstract":"<div><div>The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates various biological processes, including xenobiotic metabolism, immune response, and reproduction. Although previous studies have shown that AHR plays a role in ovarian follicle development, the precise role of oocyte-expressed AHR in female reproduction remains unclear. In this study, oocyte-specific <em>Ahr</em> knockout (cKO) mice generated by crossing the <em>Ahr</em> ^{<em>flox/flox</em>} (<em>Ahr</em> ^{<em>fl/fl</em>}) and <em>Gdf9-cre</em> transgenic mouse strains were used to answer this open question. The cKO female mice exhibited a disrupted estrous cyclicity and subfertility. Histological analyses demonstrated that oocyte AHR loss reduces the number of primary follicles while increasing the number of secondary follicles and corpus lutea in mouse ovary. Hormonal analysis revealed decreased serum estradiol and follicle-stimulating hormone, indicating a disruption of the hypothalamic-pituitary-gonadal axis in cKO mice. TUNEL and Western blotting results demonstrate that deletion of oocyte AHR also results in increased apoptosis in ovarian granulosa cells (GCs), downregulated expression of <em>Gdf9</em> and <em>Bmp15</em> in oocytes<em>,</em> and disrupted bidirectional oocyte-GC communication. In conclusion, our findings reveal that the aryl hydrocarbon receptor plays a role beyond sensing environmental chemicals and endogenous compounds and underscore a critical role of oocyte-expressed Ahr in maintain follicle development, ovarian function, and female reproductive health.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"609 ","pages":"Article 112656"},"PeriodicalIF":3.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}