Frontiers in Cell and Developmental Biology最新文献

{"title":"Review of sensory systems deployed by epidermal keratinocytes.","authors":"Mitsuhiro Denda, Peter M Elias","doi":"10.3389/fcell.2025.1598326","DOIUrl":"10.3389/fcell.2025.1598326","url":null,"abstract":"<p><p>Recent studies have shown that epidermal sensory receptors intercept and direct responses to potentially threatening environmental factors, including shifts in temperature, electric potential, sound, acidity, light, taste, and odor. In addition to stimulating epidermal responses, activation of keratinocytes by these stressors can directly signal the central nervous system. Changes in epidermal permeability barrier homeostasis also depend upon ion dynamics, particularly alterations in intraepidermal gradients of calcium (Ca²⁺) and pH. The purpose of this review is to update readers about recent advances in the field of cutaneous sensory receptors, focusing upon their roles in mediating not only permeability barrier function, but also whole-body physiology and certain aspects of mental status.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1598326"},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316355","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":"Gonadotropins differentially regulate testicular cell adhesion and junctional complexes during flatfish spermiogenesis through the oxytocin and relaxin signaling pathways.","authors":"Noelia López-Fortún, Jose Vicente Roig-Genovés, Ignacio Giménez, Joan Cerdà, François Chauvigné","doi":"10.3389/fcell.2025.1574690","DOIUrl":"10.3389/fcell.2025.1574690","url":null,"abstract":"<p><strong>Introduction: </strong>The molecular mechanisms regulating teleost semicystic spermatogenesis remain largely unknown. In the flatfish Senegalese sole (<i>Solea senegalensis</i>), haploid round spermatids released into the lumen of the seminiferous tubules resume spermiogenesis (the differentiation of germ cells into spermatozoa) in response to the luteinizing hormone (Lh). However, how the spermatids detach from Sertoli cells and how Lh crosses the blood-testis barrier (BTB) are yet to be determined.</p><p><strong>Methods: </strong>Here, we used an RNA-seq transcriptomic analysis of the testis from sole males treated with recombinant follicle stimulating hormone and Lh (rFsh and rLh, respectively).</p><p><strong>Results: </strong>This analysis reveals that both gonadotropins differentially downregulate a number of transcripts potentially encoding cell-cell junction and adhesion proteins, as well as components of the Oxytocin (Oxt) and Relaxin (Rln) signaling pathways. <i>In situ</i> hybrizidation and immunolocalization experiments confirmed the formation of adherens, gap, and tight junctions between Sertoli cells, and between Sertoli cells and spermatids. Using these methods, we also verified the expression of Oxt and Rln peptides and their cognate receptors in these cells. Further <i>in vitro</i> assays using testicular explants incubated with Oxt, Rln and inhibitors of their receptors, combined with rFsh or rLh, showed that the gonadotropic-induced transcriptional repression of cell junction and adhesion genes in the seminiferous epithelium, particularly by Lh, was largely mediated by the downregulation of Oxt and Rln signaling.</p><p><strong>Discussion: </strong>These data suggest that the Oxt- and Rln-mediated gonadotropic disruption of the BTB and Sertoli cells-spermatid junctions in the sole testis facilitates spermatid release and Lh paracellular transport into the seminiferous lumen during spermiogenesis.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1574690"},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316350","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":"Automatic detection of optic canal fractures and recognition and segmentation of anatomical structures in the orbital apex based on artificial intelligence.","authors":"Yu-Lin Li, Yu-Hao Li, Mu-Yang Wei, Guang-Yu Li","doi":"10.3389/fcell.2025.1609028","DOIUrl":"10.3389/fcell.2025.1609028","url":null,"abstract":"<p><strong>Background and objectives: </strong>Traumatic optic neuropathy (TON) caused by optic canal fractures (OCF) can result in severe visual impairment, even blindness. Timely and accurate diagnosis and treatment are crucial for preserving visual function. However, diagnosing OCF can be challenging for inexperienced clinicians due to atypical OCF changes in imaging studies and variability in optic canal anatomy. This study aimed to develop an artificial intelligence (AI) image recognition system for OCF to assist in diagnosing OCF and segmenting important anatomical structures in the orbital apex.</p><p><strong>Methods: </strong>Using the YOLOv7 neural network, we implemented OCF localization and assessment in CT images. To achieve more accurate segmentation of key anatomical structures, such as the internal carotid artery, cavernous sinus, and optic canal, we introduced Selective Kernel Convolution and Transformer encoder modules into the original UNet structure.</p><p><strong>Results: </strong>The YOLOv7 model achieved an overall precision of 79.5%, recall of 74.3%, F1 score of 76.8%, and mAP@0.5 of 80.2% in OCF detection. For segmentation tasks, the improved UNet model achieved a mean Intersection over Union (mIoU) of 92.76% and a mean Dice coefficient (mDice) of 90.19%, significantly outperforming the original UNet. Assisted by AI, ophthalmology residents improved their diagnostic AUC-ROC from 0.576 to 0.795 and significantly reduced diagnostic time.</p><p><strong>Conclusion: </strong>This study developed an AI-based system for the diagnosis and treatment of optic canal fractures. The system not only enhanced diagnostic accuracy and reduced surgical collateral damage but also laid a solid foundation for the continuous development of future intelligent surgical robots and advanced smart healthcare systems.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1609028"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301443","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":"Linoleic acid metabolite 13-Hydroxyoctadecadienoic acid as a biphasic ferroptosis modulator in granulosa cells: multi-omics analysis of ovine atretic follicles.","authors":"Yukun Song, Erhan Hai, Lixia He, Ning Zhang, Nan Zhang, Junlan Wang, Yupeng Sun, Dengke Zeng, Jiaxin Zhang","doi":"10.3389/fcell.2025.1610621","DOIUrl":"10.3389/fcell.2025.1610621","url":null,"abstract":"<p><strong>Introduction: </strong>13-Hydroxyoctadecadienoic acid (13(S)-HODE) is a bioactive lipid derived from linoleic acid, it plays prominent roles in cellular processes such as lipid metabolism, oxidative stress, and apoptosis. Follicular atresia is a complex physiological process involving multiple forms of cell death. Ferroptosis, an iron-dependent form of programmed cell death, has been less studied in the context of follicular atresia.</p><p><strong>Methods: </strong>To investigate the association between ovine follicular atresia and ferroptosis, we performed transcriptomic and metabolomic analyses of healthy and atretic sheep follicles. Notably, sheep follicular granulosa cells were treated with different doses of 13(S)-HODE. Cell viability, lipid peroxidation levels, ferroptosis-related markers, and ferroptosis-related genes were measured.</p><p><strong>Results: </strong>The metabolomic analysis identified 87 and 48 differentially expressed metabolites in healthy and atretic follicles, respectively. Functional enrichment of atretic follicle fluid highlighted pathways related to linoleic acid and purine metabolism. Transcriptomic analysis revealed 250 highly expressed genes in ovarian granulosa cells of atretic follicles. Enrichment analysis indicated that these differentially expressed genes were associated with fatty acid metabolism and ferroptosis. Integration of multi-omics data demonstrated the occurrence of ferroptosis in atretic follicles, where 13(S)-HODE drives granulosa cell ferroptosis via the linoleic acid metabolism pathway; this effect was not dose-dependent. Mechanistic studies showed that low-dose 13(S)-HODE counteracts ferroptosis by promoting glutathione peroxidase 4-mediated lipid peroxidation reduction and increasing glutathione levels.</p><p><strong>Discussion: </strong>In contrast, high-dose 13(S)-HODE induces labile iron accumulation through activation of transferrin receptor and ferritin heavy chain 1, enhancing ferroptosis sensitivity in granulosa cells. These findings provide insights into the molecular mechanisms regulating follicle development and offer potential therapeutic targets for enhanced follicular development and improved reproductive outcomes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1610621"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301460","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":"Rab21 recruits EEA1 and competes with Rab5 for Rabex-5 activation.","authors":"Francisco Yanguas, Cinzia Progida","doi":"10.3389/fcell.2025.1588308","DOIUrl":"10.3389/fcell.2025.1588308","url":null,"abstract":"<p><p>Rab5 is a key regulator of early endosomal traffic and fusion. It shares its localization and guanine nucleotide exchange factor Rabex-5 with the less characterized member of the Rab5 subfamily Rab21. Here, we found that, similarly to Rab5, Rab21 also interacts with the tethering protein EEA1. Overexpression of Rab21 rescues the defects in EEA1 localization and endosomal size caused by the depletion of PI3P or the inhibition of Rab5 function, both needed for the recruitment of EEA1 to early endosomes. Interestingly, modulation of the binding properties of Rab5 or Rab21 dominant negative mutant with Rabex-5 support a model in which Rab5 and Rab21 compete for the activation by Rabex-5 and suggest that Rab21 might have higher affinity for this GEF than Rab5 <i>in vivo</i>. Altogether, our results reveal that Rab21 regulates early endosomal size by recruiting EEA1 to the endosomes via a pathway parallel to Rab5 and highlight Rabex-5's critical role in Rab21 and Rab5 cross-regulation.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1588308"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301462","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":"Transcriptomic analysis of mammary gland tissues in lactating and non-lactating dairy goats reveals miRNA-mediated regulation of lactation, involution, and remodeling.","authors":"Yanan Peng, Xinhua Duan, Linfan Zhang, Yiyi Guo, Jinlin Cao, Weiping Ao, Rong Xuan","doi":"10.3389/fcell.2025.1604855","DOIUrl":"10.3389/fcell.2025.1604855","url":null,"abstract":"<p><strong>Background: </strong>Dynamic changes in the mammary gland during lactation and the dry period involve proliferation, secretion, apoptosis, and remodeling of mammary epithelial cells. MicroRNAs (miRNAs) are recognized as critical regulators of mammary gland development and lactation. However, their expression patterns and regulatory mechanisms at different lactation stages-particularly during mammary involution and remodeling-remain poorly understood in dairy goats.</p><p><strong>Methods: </strong>In this study, high-throughput sequencing was employed to analyze miRNA expression profiles in goat mammary tissues at five key stages: late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), and the dry period (DP). Differential expression analysis, miRNA clustering, Gene Ontology (GO) annotation, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to predict the functions of target genes. A miRNA-mRNA regulatory network associated with mammary gland development was constructed, and functional validation experiments were conducted to confirm key regulatory relationships.</p><p><strong>Results: </strong>A total of 1,120 miRNAs were identified, including 408 known and 712 newly predicted miRNAs. Among them, 383 were significantly differentially expressed, with the largest number observed between the dry period and late gestation. Six expression-specific miRNA clusters were identified. Functional enrichment analysis indicated that these miRNAs may regulate epithelial cell proliferation, apoptosis, and tissue remodeling by targeting pathways such as energy metabolism, cell adhesion, and the PI3K/Akt signaling pathway. IGF1R was identified as a key regulatory gene in the miRNA-mRNA network related to mammary gland development. Experimental validation showed that chi-miR-423-3p inhibited mammary epithelial cell proliferation, induced G1/S cell cycle arrest, and promoted apoptosis by targeting IGF1R and suppressing the PI3K/Akt pathway.</p><p><strong>Conclusion: </strong>This study highlights the dynamic regulatory roles of miRNAs in the goat mammary gland across lactation stages. Notably, the miR-423-3p/IGF1R axis is a key regulator of mammary remodeling during the dry period, offering new insights into the molecular basis of mammary gland functional transitions.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1604855"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301466","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":"Advances in research regarding epithelial-mesenchymal transition and prostate cancer.","authors":"Xi Wei, Rui Liu, Wei Li, Qi Yu, Qing Tao Yang, Tao Li","doi":"10.3389/fcell.2025.1583255","DOIUrl":"10.3389/fcell.2025.1583255","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the most prevalent cancer in men and the fifth leading cause of cancer-related mortality among men globally. Despite substantial advancements in patient prognosis attributable to improvements in PCa treatment, individuals with metastatic castration-resistant prostate cancer continue to experience poor outcomes. Epithelial-mesenchymal transition (EMT) is characterized as a cellular event in which epithelial cells adopt a mesenchymal phenotype while simultaneously losing their epithelial characteristics. EMT has been demonstrated to be associated with the progression of PCa, encompassing tumor metastasis, recurrence, drug resistance, and the development of an immunosuppressive microenvironment. Consequently, this review synthesizes recent studies on EMT in PCa, consolidating the events mediated by EMT in the progression of PCa and the molecular mechanisms linked to EMT activation in this context.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1583255"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301442","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":"A machine learning model for predicting anatomical response to Anti-VEGF therapy in diabetic macular edema.","authors":"Wenrui Lu, Kunhong Xiao, Xuemei Zhang, Yuqing Wang, Wenbin Chen, Xierong Wang, Yunxi Ye, Yan Lou, Li Li","doi":"10.3389/fcell.2025.1603958","DOIUrl":"10.3389/fcell.2025.1603958","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a machine learning model to predict anatomical response to anti-VEGF therapy in patients with diabetic macular edema (DME).</p><p><strong>Methods: </strong>This retrospective study included patients with DME who underwent intravitreal anti-VEGF treatment between January 2023 and February 2025. Baseline data included optical coherence tomography (OCT) features and blood-based metabolic and hematologic markers. The primary outcome was defined as a ≥20% reduction in central retinal thickness (CRT) post-treatment. Feature selection was performed using univariate logistic regression and LASSO regression. Five machine learning algorithms-logistic regression, decision tree, multilayer perceptron, random forest, and support vector machine-were trained and validated. Model performance was evaluated using accuracy, sensitivity, specificity, Area Under the Receiver Operating Characteristic Curve (AUC), and decision curve analysis. The best-performing model was further interpreted using SHAP analysis, and a nomogram was constructed for clinical application.</p><p><strong>Results: </strong>Among the 37 baseline variables, five key predictors were identified: preoperative CRT >400 μm, presence of retinal edema, presence of subretinal fluid (SRF), disorganization of the inner retinal layers (DRIL), and ellipsoid zone (EZ) integrity. The logistic regression model achieved the best performance with an accuracy of 0.83, sensitivity of 0.85, specificity of 0.79, and an AUC of 0.90 (95% CI: 0.81-0.99). SHAP analysis revealed that preoperative retinal edema, DRIL, SRF, and CRT had the strongest positive contributions, while intact EZ was a negative predictor of CRT reduction. A nomogram was developed to facilitate individualized clinical decision-making.</p><p><strong>Conclusion: </strong>We successfully developed a predictive model for anatomical response to anti-VEGF therapy in DME patients. The model identified key features associated with treatment outcomes, providing a valuable tool for personalized therapeutic planning. Further validation in multicenter cohorts is warranted to confirm generalizability and enhance model robustness.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1603958"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301440","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":"Adult-onset hypothyroidism induces granulosa cell apoptosis and affects ovarian follicle development in rats.","authors":"Shuyue Li, Lina Zhang, Wanqiong Li, Jiaying Qin, Lingbin Qi, Xi Xiao, Zhigang Xue, Jinfeng Xue, Yazhong Ji","doi":"10.3389/fcell.2025.1610694","DOIUrl":"10.3389/fcell.2025.1610694","url":null,"abstract":"<p><strong>Introduction: </strong>Hypothyroidism is a common endocrine disorder in women, which could lead to ovulation disorders and infertility, however, the effects of adult-onset hypothyroidism on ovarian development and gene expression characteristics need further study.</p><p><strong>Methods: </strong>Here we conducted an adult-onset hypothyroidism rat model by using the methimazole (MMI) induction, then the hormone level changes and ovarian development were evaluated, furthermore, the effects of gene expression of granulosa cells and oocytes were detected by using single-cell RNA sequencing.</p><p><strong>Results: </strong>Our results showed that, in addition to a decrease in thyroid hormones, the body weight was significantly reduced, while the estrus cycle was prolonged in the hypothyroidism group. Although the ovary/body weight ratio was not changed, the adult-onset hypothyroidism disrupted follicle development, primarily manifested by an increased number of atretic follicles and a decreased number of corpora lutea. Serum sex hormone levels were also imbalanced, with elevated LH, FSH, and PRL, while E2 and P were decreased. By combining single-cell RNA sequencing and the validation experiments, we found that adult-onset hypothyroidism promoted apoptosis in granulosa cells of antral follicles and induced oxidative stress in oocytes. Notably, we found significant heterogeneity in mitochondrial ROS in the control group, indicating differences in the redox status of different normal oocytes, which disappeared after hypothyroidism promoted oxidative stress.</p><p><strong>Discussion: </strong>In conclusion, adult-onset hypothyroidism interferes with normal follicle development and impairs fertility by promoting apoptosis in granulosa cells of antral follicles and inducing oxidative stress in oocytes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1610694"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301441","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":"Exercise benefits yourself and your offspring: a mini-review.","authors":"Kun Wang, Jiajia Zhao, Yanqiu Wang, Mairu Liu","doi":"10.3389/fcell.2025.1606790","DOIUrl":"10.3389/fcell.2025.1606790","url":null,"abstract":"<p><p>Regular physical activity is widely recognized for its systemic health benefits, extending beyond physical fitness to influence metabolism, immunity, and neurophysiology. Pregnancy is a physiologically unique period characterized by dynamic immunometabolic changes that are crucial for maternal and fetal health. Maternal exercise during this window offers a non-pharmacological strategy to enhance maternal wellbeing and optimize offspring development. This review summarizes recent advances in understanding the effects of maternal exercise on both pregnant women and their offspring. In mothers, exercise improves metabolic profiles, modulates inflammatory responses, supports neuroplasticity, and promotes skeletal health. In offspring, maternal exercise confers long-term benefits including improved glucose metabolism, enhanced neurogenesis, cognitive development, and immune resilience. Mechanistically, these effects are mediated through molecular pathways such as placental superoxide dismutase 3 (SOD3) upregulation, adenosine 5'-monophosphate-activated protein kinase/ten-eleven translocation (AMPK/TET) signaling in the fetal liver, and exercise-induced circulating factors like Apelin and SERPINA3C, which contribute to epigenetic remodeling and tissue-specific programming. Despite growing evidence, gaps remain in understanding the optimal intensity, timing, and molecular mediators of maternal exercise, particularly regarding long-term immune and neurodevelopmental outcomes in offspring. Future studies leveraging multi-omics approaches are needed to elucidate cross-organ signaling mechanisms and identify therapeutic targets to mimic exercise-induced benefits. Overall, maternal exercise emerges as a safe, accessible intervention with significant potential to improve maternal-fetal health and reduce offspring disease risk across the lifespan.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1606790"},"PeriodicalIF":4.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301459","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}