Molecular and Cellular Endocrinology最新文献

{"title":"5-HIAA alleviates lipid accumulation in rat liver caused by atrazine by promoting the activation of the AMPK/p38 signaling pathway.","authors":"Honghao Qian, Haoyan Ma, Jiaxin Zhang, Ziyu Wang, Xijun Zhang, Xiaoyu Jia, Xinyi Wang, Rui Zhao, Yinlong Zhao, Yuezhu Zhang","doi":"10.1016/j.mce.2026.112906","DOIUrl":"https://doi.org/10.1016/j.mce.2026.112906","url":null,"abstract":"<p><p>Atrazine (ATR) is one of the most widely used herbicides in global agricultural production, it enters the body mainly through drinking water and diet. Liver is the main organ of ATR metabolism. As the end product of tryptophan metabolism, 5-HIAA can regulate liver metabolism. To investigate the hepatotoxic mechanism of ATR and the rescue effect of 5-HIAA against ATR-induced hepatic lipid accumulation, Wistar rats were treated with ATR for 90 days, L02 cells were treated with ATR for 24 hours. Transcriptomic and metabolomic analyses revealed that differentially expressed genes and metabolites were enriched in non-alcoholic fatty liver disease and the tryptophan metabolic pathway, respectively. In this study, ATR suppressed the AMPK/p38 signaling pathway, inhibiting FAO and leading to hepatic lipid accumulation. Conversely, 5-HIAA indirectly modulated the activation of the AMPK/p38 signaling pathway to alleviate ATR-induced lipid accumulation and restore reduced FAO in the liver.</p>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112906"},"PeriodicalIF":3.4,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897457","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":"Exploring the Effect of Vitamin D on the Inflammatory Microenvironment of Breast Tumor in the Context of Obesity using an in vitro 3D Triculture Model.","authors":"Jessy Aoun, Ola Habanjar, Rawan Nehme, Caroline Decombat, Solène Michel, Clémence Chapuis, Christelle Blavignac, Céline Auxenfans, Mona Diab-Assaf, Florence Caldefie-Chézet, Laetitia Delort","doi":"10.1016/j.mce.2026.112908","DOIUrl":"https://doi.org/10.1016/j.mce.2026.112908","url":null,"abstract":"<p><p>Obesity is a recognized risk factor for breast cancer, the leading cause of cancer death worldwide. Vitamin D (vit D), a molecule with anti-inflammatory effects, can act on different cell types through the presence of its VDR receptor. Our aim was therefore to study the impact of vit D in a 3D co-culture model between PreAd (spheroids of pre-adipocytes from obese women) or Mat-Ad (spheroids of mature adipocytes from obese women), M1-like pro-inflammatory macrophages and mammary cancer spheroids, to mimic the inflammatory breast tumor microenvironment (TME) of a person with obesity. The results showed a decrease in the expression of adipocyte differentiation genes in PreAd, inflammatory cytokines genes in inflammatory macrophages and tumor proliferation genes in cancer spheroids in the coculture system with PreAd, M1-macrophages and cancer cells. In addition, there was a decrease in the secretion of certain key inflammatory cytokines involved in obesity thus decreasing the overall inflammation of the microenvironment. These results were not observed in the coculture with Mat-Ad, M1-macrophages and cancer cells, with little to no effect of vit D on gene expression and an increase of the secretion of key inflammatory cytokines involved in obesity in the microenvironment thus favoring inflammatory microenvironment. These results suggest that, at a physiological concentration, vit D has therefore a more pronounced action on PreAd. Our findings suggest that the effects of vit D on TME depend on adipocyte differentiation, with potential benefits in preadipocytes rich microenvironment but limited efficacy in mature adipocytes rich microenvironment. Further studies are needed to determine the therapeutic relevance of vit D supplementation.</p>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112908"},"PeriodicalIF":3.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892101","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":"Fibroblast Growth Factor 23 (FGF23): From Synthesis to Cleavage.","authors":"Shusen Yuan, Qi Wang, Chao Meng, Hongjie Ji, Baowei Li","doi":"10.1016/j.mce.2026.112909","DOIUrl":"https://doi.org/10.1016/j.mce.2026.112909","url":null,"abstract":"<p><p>Fibroblast growth factor 23 (FGF23) maintains phosphate and vitamin D homeostasis. In the kidney, recognition of FGF23 is mediated by fibroblast growth factor receptors (FGFRs), α-Klotho, and heparan sulfate. Structural studies indicate that an FGF23-FGFR-α-Klotho recognition unit recruits a second FGFR with assistance from heparan sulfate to form an asymmetric 1:2:1:1 complex that activates Ras-mitogen-activated protein kinase (MAPK) signaling. Circulating intact FGF23 reflects transcription, post-translational processing, secretion, and clearance. In FGF23-producing cells, polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3)-mediated O-glycosylation at Thr178 protects the cleavage site, whereas phosphorylation of Ser180 by FAM20C, a Golgi-associated secretory pathway kinase, limits this protection. Furin and related proprotein convertases cleave FGF23 within the secretory pathway, although their in vivo contributions remain unresolved. In cell-free experiments, tissue-type and urokinase-type plasminogen activators directly cleave recombinant FGF23; mouse data also implicate the plasminogen activator inhibitor-1 axis, but its quantitative contribution to the human circulating pool is unknown. Receptor availability further shapes signaling. Although osteocytes and osteoblasts are the principal endocrine sources, human skin cells express and secrete FGF23 in vitro. Their response to 1,25-dihydroxyvitamin D₃ depends partly on the vitamin D receptor, but whether skin contributes to circulating FGF23 remains undefined. Chronic kidney disease, autosomal dominant hypophosphatemic rickets, hyperphosphatemic familial tumoral calcinosis, X-linked hypophosphatemia, Raine syndrome, and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency illustrate the relationships among FGF23 processing, bone-matrix signaling, and pyrophosphate homeostasis. This review integrates these mechanisms and evaluates burosumab, selective FGFR inhibition, C-terminal peptides, small-molecule antagonists, and ENPP1 enzyme replacement according to current evidence.</p>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112909"},"PeriodicalIF":3.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892096","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":"Glucose and serum availability fine-tune neuronal metabolic adaptations and direct insulin signaling.","authors":"Lotte Reinecke, Hannah Rumpel, J Sophie Messner, Sarah Ertel, Lydia Häußler, Sahar Cheshmeh, Melanie Krass, Kai Kappert, Robert Hauffe, André Kleinridders","doi":"10.1016/j.mce.2026.112898","DOIUrl":"10.1016/j.mce.2026.112898","url":null,"abstract":"<p><p>Cell culture systems are indispensable tools for studying cellular metabolism and signaling. However, subtle variations in nutrient composition, serum content, culture duration, and handling can influence cellular physiology. Despite widespread use, conditions commonly regarded as \"standard\" are rarely systematically evaluated for their impact on metabolic and insulin signaling pathways. Here, we systematically examined the effects of glucose concentration, fetal bovine serum (FBS) levels, culture duration, and medium volume on metabolic dynamics, stress responses, and insulin signaling in the hypothalamic cell line CLU468. Continuous oxygen consumption monitoring was combined with acute mitochondrial function assays and molecular analyses of stress pathways, autophagy, apoptosis, and insulin-responsive signaling cascades, including AKT and ERK activation. Prolonged culture duration alone (72 h vs. 24 h) reduced insulin receptor phosphorylation by approximately 70% and AKT activation by 77%. Continuous oxygen monitoring revealed distinct metabolic profiles dependent on glucose and serum availability: serum deprivation caused early stagnation of oxygen consumption and robust activation of autophagy and apoptosis, whereas glucose restriction permitted a delayed but ultimately more severe energy crisis, coinciding with pronounced cell death. Acute insulin signaling was shaped by a significant interaction between culture time and media condition, such that prolonged culture shifted the balance of AKT and ERK activation towards ERK dominance in standard conditions, but towards AKT dominance under glucose or serum restriction. Increasing medium volume did not uniformly delay these signaling shifts, but altered their direction in a condition-specific manner, while supplementation with the fatty acid palmitate selectively extended mitochondrial function in conditions with sufficient serum support. Key aspects of this nutrient- and time-dependent regulation, including the time-dependent decline in insulin signaling and its shift in AKT/ERK balance, were conserved in the insulin-sensitive pre-adipocyte line 3T3-L1 and were robust across multiple FBS lots. These findings demonstrate that routine culture parameters are active determinants of cellular metabolic state and shape insulin-induced metabolic versus mitogenic signaling by altering the pAKT/pERK balance, and that this regulation extends beyond a single cell type. Careful consideration and reporting of culture conditions are therefore essential for the interpretation and reproducibility of neuroendocrine and metabolic studies.</p>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":" ","pages":"112898"},"PeriodicalIF":3.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881069","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":"Growth hormone enhances mitochondria biogenesis and endows mitochondrial thermogenesis in murine adipocytes","authors":"Esha Sadiq ,&nbsp;Yinghao Liu ,&nbsp;Ni Li ,&nbsp;Chen Zong ,&nbsp;Xiaojie Li ,&nbsp;Tianfu Yu ,&nbsp;Zeqing Pu ,&nbsp;Luqman Alameri ,&nbsp;Zhuoxuan Li ,&nbsp;Siying Li ,&nbsp;Xiangdong Wang ,&nbsp;Ruxing Zhao","doi":"10.1016/j.mce.2026.112758","DOIUrl":"10.1016/j.mce.2026.112758","url":null,"abstract":"<div><div>Growth hormone (GH) can reduce the size of white adipocytes in vivo and in vitro. This catabolic effect was previously believed to be related to the breakdown of stored triglycerides into free fatty acids. However, little is known about its effects on mitochondria in adipose or adipocytes. We thus examined effects of GH on mitochondrial number change and metabolic changes in fat of diet induced obese mice as well as 3T3-L1 adipocytes. We first found in vitro GH increase the density of mitochondria in 3T3-L1 adipocytes. We figured out that GH enhanced the expression of mitochondria biogenesis related genes, such as peroxisome proliferative activated receptor gamma coactivator 1 alpha (Pgc1α), DNA polymerase gamma (Polg) and transcription factor A of mitochondria (Tfam) in vitro and in vivo. To explore the underlying mechanism, we further confirmed that the enhanced expression of these proteins was dependent on the three pathways of GH signaling transduction and that GH enhanced the promoter transactivation of Pgc1α or Polg. We also found that GH increased the cell death-inducing DNA fragmentation factor alpha subunit-like effector A (CIDEA) and uncoupling protein 1 (UCP1) expression by enhancing the promoter transactivation of Cidea. We further elucidated that GH induced UCP1 expression was dependent on CIDEA using CRISPR-Cas9 technique. We therefore conclude that GH has effects on reducing adipocyte size via promoting PGC1α and POLG mediated mitochondrial biogenesis, and also on increasing UCP1 expression via CIDEA. Making adipocytes browning by GH or its analogs may provide a therapeutic strategy for metabolic diseases.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"616 ","pages":"Article 112758"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146161780","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":"Estradiol promotes trophoblasts syncytization by upregulating ESR2/SP1 transcription factor-mediated poFUT2 expression","authors":"Yaqi Li ,&nbsp;Yuyu Lei ,&nbsp;Yu Chen ,&nbsp;Luyao Wang ,&nbsp;Yanbo Wang ,&nbsp;Wenbo Wang ,&nbsp;Jiao Wang ,&nbsp;Shuai Liu","doi":"10.1016/j.mce.2026.112757","DOIUrl":"10.1016/j.mce.2026.112757","url":null,"abstract":"<div><div>The multinucleated syncytiotrophoblast (STB) at the maternal-fetal interface is formed through the continuous fusion of mononucleated cytotrophoblasts (CTBs). Estradiol and protein glycosylation are known to participate in trophoblast syncytialization. O-fucosyltransferase 2 (poFUT2), which catalyzes protein O-fucosylation, has been implicated in placental development. However, the exact role of poFUT2 in trophoblast syncytialization remains unclear. The aim of the present study is to investigate the function of the estradiol-poFUT2 axis in trophoblast syncytialization. Here, by applying immunohistochemistry, we found that poFUT2 expression was decreased in syncytiotrophoblast of placental tissues from preeclampsia patients. Employing a cell-model to induce trophoblast syncytialization <em>in vitro</em>, we demonstrated that poFUT2 promotes trophoblast cell fusion. Mechanistically, during pregnancy, elevated estradiol upregulated the expression of poFUT2 and enhanced syncytium formation. Chromatin immunoprecipitation and co-immunoprecipitation assays indicated that the regulation depends on the participation of SP1 in the estrogen receptor 2 (ESR2)-mediated regulation of the poFUT2 gene. Conclusively, our findings demonstrated that estradiol upregulated poFUT2 expression via the ESR2/SP1 complex, increasing trophoblast cell differentiation and fusion.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"616 ","pages":"Article 112757"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165878","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":"Thyroid hormones drive central nervous system remodelling during flatfish metamorphosis","authors":"Aurora Olvera ,&nbsp;Carlos Carballo ,&nbsp;I. Lazcano ,&nbsp;Aurea Orozco ,&nbsp;Manuel Manchado ,&nbsp;Deborah Mary Power","doi":"10.1016/j.mce.2026.112759","DOIUrl":"10.1016/j.mce.2026.112759","url":null,"abstract":"<div><div>Flatfish metamorphosis is an abrupt post-embryonic transformation driven by thyroid hormones (THs), in which a bilaterally symmetric pelagic larvae becomes an asymmetric benthic juvenile. While the craniofacial changes associated with eye migration during metamorphosis are well documented, the role of THs in central nervous system (CNS) remodelling remains poorly understood. Here we investigated the role of THs on CNS remodelling during metamorphosis of the flatfish, <em>Solea senegalensis</em>, by integrating high-throughput transcriptomic analysis with experimental manipulation of TH availability using an inhibitor of hormone synthesis, methimazole (MMI) or exogenous T4. Transcriptome profiling revealed 567 differentially expressed gene transcripts associated with TH-levels involved in CNS development, neuronal and glial differentiation, migration, myelination and metabolism. Key CNS-related factors such as <em>klf9</em>, <em>sox9</em>, <em>mbp</em>, and <em>plp</em> were strongly down-regulated in MMI-treated larvae. Cell proliferation assays further demonstrated increased interocular neural proliferation under hypothyroidism, consistent with impaired differentiation. Region-specific analyses of the head and body uncovered distinct patterns of TH signalling involving <em>dio2</em>, <em>dio3</em>, <em>thra</em>, <em>thrb</em>, and <em>mct8,</em> underscoring the spatial complexity of endocrine regulation. These results highlight that THs are crucial for both morphological remodelling and CNS plasticity during flatfish metamorphosis, underscoring their conserved role in vertebrate brain development.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"616 ","pages":"Article 112759"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181100","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":"Comparative analysis of melatonin and sildenafil in a rat model of pulmonary arterial hypertension: Insights into oxidative stress, inflammation, and mitochondrial biogenesis","authors":"Silvio Tasca,&nbsp;Patrick Türck,&nbsp;Daniela Drosdowski,&nbsp;Cristina Campos Carraro,&nbsp;Adriane Belló-Klein,&nbsp;Alexandre Luz de Castro,&nbsp;Alex Sander da Rosa Araujo","doi":"10.1016/j.mce.2026.112760","DOIUrl":"10.1016/j.mce.2026.112760","url":null,"abstract":"<div><div>Pulmonary artery hypertension (PAH) is characterized by increased pulmonary vascular resistance, leading to the augmented afterload of the right ventricle (RV), hypertrophy, and heart failure. Oxidative stress and inflammation in the RV may be involved in the physiopathology of PAH. Because of their antioxidant properties, melatonin and sildenafil could be possible therapeutic agents for the treatment of PAH. Therefore, the present study evaluated the protective effects of melatonin against oxidative stress, inflammation, and mitochondrial biogenesis in the RV of rats with PAH. Wistar rats were divided into four groups: control (CTR), monocrotaline (MCT), monocrotaline treated with sildenafil (MCT + SIL), and monocrotaline treated with melatonin (MCT + MEL). PAH was induced using a single dose of MCT (60 mg/kg, i. p.). Sildenafil citrate (50 mg/kg/day) and melatonin (10 mg/kg/day) were then administered by gavage, beginning on the first day of the experimental protocol. On the day 21, echocardiographic, morphometric, oxidative/nitrosative stress and Western blotting analyses were performed. Animals that received melatonin or sildenafil demonstrated an increased tricuspid annular plane systolic excursion (TAPSE) when compared with non-treated animals, indicating an improvement in RV contractility. Both melatonin and sildenafil treatment decreased lipid peroxidation (LPO) and reestablished sulfhydryl levels. Melatonin administration decreased the protein expression level of nuclear factor kappa beta (NF-κB), while sildenafil decreased xanthine oxidase expression. Both treatments increased peroxisome proliferator activated receptor gamma co-activator 1 alpha (PGC-1α) expression. Based on our findings, melatonin showed a protective effect similar to sildenafil in the RV of a rats model of PAH.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"616 ","pages":"Article 112760"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146181030","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":"Triploidy alters hormonal and paracrine signaling to promote male development in zebrafish","authors":"Aarón Torres-Martínez ,&nbsp;Tomáš Tichopád ,&nbsp;Martin Pšenička ,&nbsp;Roman Franěk","doi":"10.1016/j.mce.2026.112740","DOIUrl":"10.1016/j.mce.2026.112740","url":null,"abstract":"<div><div>Sex differentiation in zebrafish is governed by a complex interplay of genetic and endocrine signals. Triploid zebrafish, which are largely sterile, consistently develop as males, but the underlying mechanisms remain elusive. Here, we combined histological and transcriptomic analyses to examine how triploidy and exposure to 17α-ethinylestradiol (EE2) modulate sex differentiation in zebrafish. Triploidy disrupted hormonal and paracrine signaling, with downregulation of <em>fshr</em> and <em>amh</em>, upregulation of <em>igf3</em>, potential activation of β-catenin pathway, and suppression of <em>ptger2a</em> and <em>dio1</em>, resulting in complete masculinization. In diploids, EE2 exposure resulted in a wide range of gonadal phenotypes, from testes and ovotestes to fully developed ovaries, reflecting the complexity and variable sensitivity of zebrafish sex differentiation to hormonal stimuli. Potential mechanistic insights underlying these outcomes are provided. By contrast, long exposure of triploid zebrafish to EE2 promoted the expansion of early germ cells, but failed to induce ovarian differentiation, suggesting a fixed male trajectory induced by triploidy. Triploids also showed a distinct endocrine state, lacking the EE2-induced suppression of <em>cyp11c1</em> observed in diploids, suggesting altered corticosteroid homeostasis that may reinforce masculinization. Both triploidy and EE2 administration altered meiosis and spermiogenesis, consistent with the downregulation of <em>klhl10</em> and constrained retinoic acid signaling through <em>dhrs3a</em> and/or <em>cyp26b1</em>. At the molecular level, both triploidy and EE2 converged on suppression of early steroidogenic genes, including <em>star</em> and <em>cyp11a1</em>, indicating limited androgen and estrogen biosynthesis. Together, these findings reveal how triploidy reshapes endocrine regulation and responsiveness and reveal shared and unique molecular pathways by which EE2 influences zebrafish gonadal fate.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112740"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086448","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":"The impact of maternal vitamin D deficiency during pregnancy and lactation on autism-like behavior in offspring","authors":"Xiao-Yue Song ,&nbsp;Hong-Ning He ,&nbsp;Lin-Jing Tuo ,&nbsp;Bo Wang ,&nbsp;Heng Zhang ,&nbsp;De-Xiang Xu","doi":"10.1016/j.mce.2026.112737","DOIUrl":"10.1016/j.mce.2026.112737","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments and stereotyped behaviors. Many epidemiological studies have found a potential relationship between vitamin D deficiency (VDD) and ASD. However, the mechanism remains unclear. In this study, a VDD model was established by feeding a vitamin D-depleted diet to 5-week-old female mice, from their adulthood through pregnancy to end of lactation. Social deficits, repetitive stereotyped behaviors and anxiety-like behaviors were evaluated in the offspring. The results showed the number of buried marbles was increased in the female offspring of the VDD group. Social defects were observed in both male and female offspring in the VDD group. Mechanistically, several markers of cell proliferation, such as Pcna and Ki67, were upregulated. And the number of TBR2⁺ cell, an intermediate progenitor cell, was increased in cerebral cortex of VDD-fed fetuses. Moreover, DKK1, a WNT/β-catenin pathway repressor, was elevated in cerebral cortex of VDD-fed fetuses. By contrast, β-catenin, a critical effector of the WNT/β-catenin pathway, was reduced in cerebral cortex of GD14 VDD fetuses. These results provide partial evidence that maternal vitamin D deficiency during pregnancy and lactation induces autism-like behaviors partly by suppressing WNT/β-catenin pathway in the cerebral cortex.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"615 ","pages":"Article 112737"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097225","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}