Frontiers in Cell and Developmental Biology最新文献

{"title":"Embryo-derived trypsin-induced calcium entry is inhibited by endometrial infertility factor, LEFTY2.","authors":"Zhiqi Yang, Jing Yan, Steffen Kull, Md Alauddin, Sara Y Brucker, Melanie Henes, Florian Lang, Madhuri S Salker","doi":"10.3389/fcell.2025.1499339","DOIUrl":"10.3389/fcell.2025.1499339","url":null,"abstract":"<p><strong>Introduction: </strong>A transient window of uterine receptivity ensures that embryos implant in an optimal endometrial environment. Failure to establish or premature closure of the implantation window is thought to be a major cause of infertility, which affects many couples globally. Embryos release trypsin, which designates its developmental potential and plays a crucial role in implantation. Calcium (Ca²⁺) signalling participates in receptivity and is thus a prerequisite for embryo implantation. Left-right determination factor 2 (LEFTY2) is a negative regulator of endometrial receptivity and is associated with unexplained infertility. We hypothesize that LEFTY2 impedes Ca²⁺ entry induced by trypsin in endometrial cells.</p><p><strong>Methods: </strong><i>In silico</i> analysis was performed to investigate classical trypsin pathway genes in human embryos. Trypsin levels from single human embryo conditioned medium were subject to ELISA. To determine if trypsin signals can modulate calcium entry, intracellular calcium [Ca²⁺]_i was determined utilizing Fura-2 fluorescence in human endometrial epithelial cells (Ishikawa cells). Bioinformatic analysis on publicly available single cell sequencing data was used to investigate the expression of <i>L-type calcium channel (CACNA1C)</i> in endometrium. qRT-PCR and immunofluorescence were used to quantify L-type calcium channel abundance.</p><p><strong>Results: </strong>We report that the trypsin machinery is established at the blastocyst stage and that high levels of trypsin are associated with a successful pregnancy. Treatment with LEFTY2 or combined treatment with LEFTY2 and trypsin blocked the increase of L-type Ca²⁺ channel levels and activity. Treatment of endometrial cells with trypsin was followed by an increase of [Ca²⁺]_i, an effect that was significantly blunted by amiloride and LEFTY2. Further, the trypsin induced increase of [Ca²⁺]_i was significantly blunted by L-type calcium channel inhibitor nifedipine. In the presence of nifedipine, LEFTY2 did not further modify trypsin induced increase of [Ca²⁺]_i. LEFTY2 significantly decreased levels of L-type Ca²⁺ channel.</p><p><strong>Discussion: </strong>Taken together, we demonstrate that high trypsin levels are associated with a positive pregnancy outcome and that infertility factor LEFTY2 downregulates trypsin induced Ca²⁺ increase due in part by interference with nifedipine sensitive Ca²⁺ entry. These findings contribute further to our knowledge of unexplained infertility and failed assisted reproductive technologies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1499339"},"PeriodicalIF":4.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283340","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":"Editorial: Guanine nucleotide exchange factors as determinants of cell fate and development.","authors":"Vegesna Radha, Katsuhiko Tabuchi, Jacek Z Kubiak","doi":"10.3389/fcell.2025.1629906","DOIUrl":"10.3389/fcell.2025.1629906","url":null,"abstract":"","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1629906"},"PeriodicalIF":4.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283338","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 comprehensive overview of focused ion beam-scanning electron microscopy (FIB-SEM) applications for the evaluation of outer retina.","authors":"Sanjay Ch, Rayne R Lim, Shermaine W Y Low, Deana G Grant, Sam Patterson, Aparna Ramasubramanian, Ashish K Gadicherla, Shyam S Chaurasia","doi":"10.3389/fcell.2025.1586029","DOIUrl":"10.3389/fcell.2025.1586029","url":null,"abstract":"<p><p>The retina is the light-sensitive inner layer of the eye, consisting of multiple cell types organized into ten distinct layers of neurons interconnected by synapses that play a crucial role in visual function. Any pathological alterations in this intricate structure can lead to vision impairment. Conventional electron microscopy techniques, including scanning electron microscopy (SEM) and transmission electron microscopy (TEM), provide our current understanding of ultrastructural defects in the retina. However, they are limited by their inability to image the complex three-dimensional (3D) structure layer-by-layer at a nanoscale resolution. Advanced electron microscopy techniques, including serial block face scanning (SBF), have emerged as a superior alternative to traditional imaging methods for enhancing the understanding of 3D segmentation at the nanoscale and revealing the ultrastructural architecture of the retina under both physiological and pathological conditions. This article provides a comprehensive overview of the advancements in SBF electron microscopy, emphasizing focused ion beam (FIB)-SEM for studying the interdigitation zone (IZ), which connects the cone outer segments to the retinal pigment epithelium (RPE) to enhance the understanding of retinal degenerative diseases such as inherited retinal disorders (IRDs), age-related macular degeneration (AMD), and diabetic retinopathy (DR). We have collated and discussed current literature alongside our recent work on FIB-SEM applications, particularly in examining the structural integrity of the outer retina. FIB-SEM can bridge the knowledge gap between structural insights and functional impairments through its state-of-the-art imaging and 3D segmentation capabilities. Additionally, it offers various applications for the pathological evaluation of retinal degenerative diseases.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1586029"},"PeriodicalIF":4.6,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12158942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283337","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":"Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model.","authors":"Lina Zhang, Jing Jin, Liguang Sun, Gang Hou, Mingming Deng, Yiding Bian, Jianming Liu, Wei Cheng, Shaoliang Xing, Wenjia Wang, Xin Dong, Qingjie Fan, Lei Gao, Xinhua Lei, Yongli Bao, Yongguang Yang","doi":"10.3389/fcell.2025.1550447","DOIUrl":"10.3389/fcell.2025.1550447","url":null,"abstract":"<p><strong>Introduction: </strong>The clinical translation of mesenchymal stem cell-derived exosome faces critical challenges in scalable production, subpopulation stability, and therapeutic route optimization. This study systematically addresses these barriers to advance exosome-based therapies.</p><p><strong>Methods: </strong>We established a 28-day biomanufacturing workflow using a Hollow Fiber 3D bioreactor integrated with the RoosterBio exosome-harvesting system. Exosomes were subsequently purified and rigorously characterized at multiple production stages, followed by isotopically labeled with ⁸⁹Zr for biodistribution studies. Therapeutic efficacy was evaluated in a silica-induced mouse silicosis model comparing intravenous and respiratory administration routes.</p><p><strong>Results: </strong>Our findings indicate that (1) the RoosterBio exosome harvesting system in the Hollow Fiber 3D bioreactor enables 28 days production of exosomes, with stable harvesting of the main subpopulations over a certain period; (2) systemic administration via intravenous injection in rats reveals distinct tissue tropism, with isotope-labeled exosomes exhibiting predominant hepatic accumulation; and (3) in the silica-induced mouse silicosis model, respiratory delivery of exosomes significantly improves disease progression, whereas intravenous infusion of exosomes does not yield notable therapeutic effects.</p><p><strong>Discussion: </strong>This study proposes a holistic workflow for early-stage development of natural exosomes as therapeutics, offering guidance on industrial-scale production, purification, and characterization of exosomes with stable subpopulation distribution and functional consistency. It further addresses administration route selection in pulmonary disease animal models and heterogeneity assessment of natural exosomes. These advancements facilitate clinical translation of exosome-based therapies.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1550447"},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265856","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":"Long-term muscarinic inhibition increases intrinsic excitability through the upregulation of A-type potassium currents in cortical neurons.","authors":"Denise Riquelme, Patricia Romo-Toledo, Paula Leyton, Claudio Moreno, Elias Leiva-Salcedo","doi":"10.3389/fcell.2025.1570424","DOIUrl":"10.3389/fcell.2025.1570424","url":null,"abstract":"<p><p>Neurons undergo a series of perturbations that alter their firing rate and synaptic transmission; however, they can adapt to keep a target level of electrical activity in the long term. Muscarinic receptor (mAChR) transmission modulates intrinsic excitability and allows for fast changes through phasic transmission and long-term effects through volume transmission. Earlier studies on mAChR transmission have primarily focused on the effects of long-term mAChR stimulation on excitability; however, the impact of long-term inhibition is still unknown. In this study, we used a combination of patch-clamp and immunofluorescence techniques to examine the effects short-term (3 h) and long-term (0-10 days) muscarinic or nicotinic (nAChR) receptor inhibition on the intrinsic excitability of cortical pyramidal neurons in culture. We found that short term mAChR or nAChR inhibition has no effect either in AIS or in neuronal excitability, however, prolonged mAChR, but not nAChR blockade, increases the AIS length with no change in its position. Moreover, prolonged mAChR blockade increases firing frequency and intrinsic excitability, through a reduction in the action potential duration that is the result of an increase in a 4-AP sensitivity K⁺ current in cortical pyramidal neurons in culture. Together, our work demonstrates that prolonged mAChR, but not nAChR, blockade induces structural and functional changes to compensate for the lack of mAChR signaling and to sustain a target level of electrical activity.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1570424"},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265855","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":"Emerging roles for E3 ubiquitin ligases in neural development and disease.","authors":"Maya Hale, Greg J Bashaw","doi":"10.3389/fcell.2025.1557653","DOIUrl":"10.3389/fcell.2025.1557653","url":null,"abstract":"<p><p>Neurodevelopment is an intricate process with highly regulated, overlapping stages including neuronal differentiation and axon guidance. Aberrations during these and other stages are tied to the etiology of neurodevelopmental disorders like Autism Spectrum Disorder, Angelman Syndrome, and X-linked Intellectual Disability. Ubiquitination is a dynamic and highly reversible post-translational modification conferred by E3 ubiquitin ligases. Recent discoveries have advanced the understanding of how substrate ubiquitination can guide protein localization, drive protein degradation, and alter protein post translational modifications. In this review, we highlight members of the RING and HECT E3 ligase families to discuss their novel roles in the molecular mechanisms regulating neurodevelopment. These findings are both instrumental for informing the future directions of neurodevelopmental research, and in expanding knowledge of intracellular mechanisms of protein trafficking. In addition, a deeper understanding of the molecular mechanisms of E3 ligase function in development promises to offer new insights into the pathogenesis of neurodevelopmental disorders.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1557653"},"PeriodicalIF":4.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265854","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":"Early detection of retinal and choroidal microvascular impairments in diabetic patients with myopia.","authors":"Yufei Wu, Jiahui Jiang, Xiaoyu Deng, Xixi Zhang, Jinger Lu, Zian Xu, Yitian Zhao, Zai-Long Chi, Qinkang Lu","doi":"10.3389/fcell.2025.1609928","DOIUrl":"10.3389/fcell.2025.1609928","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate and quantify diabetes-related retinal and choroid perfusion changes in individuals with and without high myopia and explore their associations with diabetes risk factors.</p><p><strong>Methods: </strong>Diabetic patients [n = 133; 43 without diabetic retinopathy in group DM; 48 non-proliferative diabetic retinopathies in group DR; 42 without DR but with high myopia in group HM] underwent ophthalmological and endocrinological examinations. Swept-source optical coherence tomography angiography (SS-OCTA) was used to image the retinal vessel density (RVD), retinal thickness (RT), choroidal thickness (CT), choriocapillaris vessel perfusion (CPV) and choroidal vascularity index (CVI). Automatic segmentation of retinal and choroidal layers was performed using a deep learning-based U-Net architecture. A ResNet-50 convolutional neural network was further applied to analyze vascular density patterns and assist in DR grading. Univariate and multiple linear regression analyses explored the associations between perfusion and risk factors.</p><p><strong>Results: </strong>The inner ring retinal vessel density and CVI in all areas were significantly different between groups (<i>P</i> < 0.05); CPV was not significantly changed except for the inferotemporal area among the groups. CT was decreased in all areas between groups (<i>P</i> < 0.05). The visual impairments in HM group was more obvious correlation with the retinal and choroidal structural changes. The AI-driven analysis revealed that decreased CVI and CT were significantly associated with age and spherical equivalent (SE), highlighting the utility of automated algorithms in identifying early microvascular impairments.</p><p><strong>Conclusion: </strong>Diabetic patients with high myopia exhibited significantly lower CVI compared to those with diabetic retinopathy, indicating that CVI monitoring could facilitate risk stratification of diabetic retinopathy progression. The integration of SS-OCTA with artificial intelligence-enhanced segmentation and vascular analysis provides a refined method for early detection of retinal and choroidal microvascular impairments in diabetic populations.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1609928"},"PeriodicalIF":4.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257770","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":"<i>Morinda officinalis</i> oligosaccharides attenuate mitochondria-associated ferroptosis via the NOX4/mitoGPX4 pathway in myocardial ischemia‒reperfusion injury.","authors":"Yuqiong Chen, Yuan Tian, Bo Guan, Yiling Chang, Xiaopei Yan, Qi Song, Wenting Chen, Lin Chen, Wei Li, Wenjun Mao, Yan Zhang, Chao Chen, Su Li","doi":"10.3389/fcell.2025.1605513","DOIUrl":"10.3389/fcell.2025.1605513","url":null,"abstract":"<p><strong>Aim: </strong>To explore the benefits of <i>Morinda officinalis</i> oligosaccharides (MOO) on ischemia-reperfusion (I/R) injury and the possible mechanisms involved.</p><p><strong>Methods: </strong>Myocardial I/R injury were induced by left anterior descending branch ligation. MOO pretreatment was given orally 2 weeks prior to ischemic treatment. Echocardiograms, biochemical parameters, and histological and immunohistochemical analyses were used to determine the benefits of MOO on myocardial I/R injury. Oxidative stress and ferroptosis were examined by biochemical parameters, Western blot, immunohistochemistry, and Tunel staining.</p><p><strong>Results: </strong>MOO improved cardiac function and reduced myocardial oxidative stress and ferroptosis, which was associated with the inhibition of NADPH Oxidase 4 (NOX4) expression. Whereas, the upregulation of NOX4 abolished the benefits of MOO. Furthermore, MOO enhanced mitochondrial superoxide dismutase 2 (SOD2) activity and stimulated the mitochondrial translocation of glutathione peroxidase 4 (mitoGPX4) by inhibiting NOX4. Mitochondria-specific GPX4 overexpression attenuated mitochondrial oxidative stress and suppressed mitochondria-associated ferroptosis in cardiomyocytes that suffered from hypoxia-reoxygenation (H/R) injury, even after NOX4 overexpression.</p><p><strong>Conclusion: </strong>These results indicate the beneficial effects of MOO on myocardial I/R injury by suppressing oxidative stress and mitochondria-associated ferroptosis through NOX4/mitoGPX4 pathway.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1605513"},"PeriodicalIF":4.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257769","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":"Targeting fibroblasts in pathological bone formation: mechanisms and treatments.","authors":"Qianyu Zhang, Qimin Song, Zeyin Li, Xinyi Wu, Yuxiong Chen, Hui Lin","doi":"10.3389/fcell.2025.1612950","DOIUrl":"10.3389/fcell.2025.1612950","url":null,"abstract":"<p><p>Fibroblasts are integral to the pathological processes underlying abnormal bone formation, including heterotopic ossification (HO), ankylosing spondylitis (AS), and ossification of the posterior longitudinal ligament (OPLL). This review summarized the diverse roles of fibroblasts, from their transdifferentiation into osteoblast-like cells to their influence on inflammatory and mechanical signal transduction pathways, including those mediated by BMP, TGF-β, and Wnt/β-catenin. In particular, senescent fibroblasts can secrete Activin A to activate the BMP pathway to drive HO formation, and fibroblasts can also differentiate into osteoblasts via interactions among the TGF-β1, BMP-2, and FGF-2 pathways. In AS and OPLL, fibroblasts respond to inflammatory signals and mechanical stress, contributing to pathological bone formation through extracellular matrix remodeling and osteogenic gene expression. In rare cases, fibroblast-mediated abnormal ossification also occurs in diffuse idiopathic skeletal hyperostosis (DISH) and systemic sclerosis (SSc). Therapeutic strategies targeting fibroblast signaling pathways, inflammation, and senescence are highlighted as potential interventions to mitigate these conditions.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1612950"},"PeriodicalIF":4.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257771","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":"Impact of hyperglycaemia on cellular microenvironment and function of endometrium and uterine tube: scoping review focused on infertility in diabetic women.","authors":"Peter Jackuliak, Martin Jankovský, Magdaléna Kovářová, Jaroslav Voller, Claudia Feitscherová, Ivan Varga","doi":"10.3389/fcell.2025.1582039","DOIUrl":"10.3389/fcell.2025.1582039","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes mellitus (DM) and associated comorbidities correspond to female infertility by many interrelated mechanisms. Yet most prior research focuses only on ovary dysfunction. Our work evaluates literature mechanisms of DM-induced uterine tube and endometrial dysfunction, corresponding impacts on female fertility, and potential evidence-based intervention targets.</p><p><strong>Methods: </strong>We conducted a scoping review (mapping review) follows the Joanna Briggs Institute (Manual for Evidence Synthesis, 2020 version). After identifying the research questions, we conducted a comprehensive search across four electronic databases by entering the keyword \"diabetes\", with a combination with other keywords as the uterus, endometrium, uterine/Fallopian tube, infertility and embryo implantation. We excluded manuscripts that address the issue of gestational diabetes. Most of these studies were in animals.</p><p><strong>Results: </strong>There is compelling evidence for connecting DM with uterine tube infertility <i>via</i> endometriosis, thyroid dysfunction, and susceptibility to infectious disease. DM damages the endometrium before pregnancy <i>via</i> glucose toxicity, lesions, excessive immune activity, and other mechanisms. DM also hinders endometrium receptivity and embryo-endometrium crosstalk, such as through disrupted endometrium glucose homeostasis. We also hypothesize how DM may affect the function of immune cells in uterine tube and uterus, including changes in the number and types of cells of innate and acquired immunity, disrupting immunological barrier in uterine tube, alterations in formation of neutrophil extracellular traps or polarization of macrophages.</p><p><strong>Discussion: </strong>We discuss evidence for clinical practice in terms of glycaemic control, lifestyle modifications, and medical interventions. For example, there is currently substantial evidence from rodent models for using metformin for increase in endometrial thickness, number of stromal cells and blood vessels and restoration of normal endometrial architecture, and bariatric surgery for recruitment of protective immune cell types to the endometrium. We also briefly highlight the future prospects of stem cells, artificial intelligence, and other new approaches for managing DM-associated female infertility. Further studies are necessary for optimizing female reproductive outcomes.</p>","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1582039"},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247301","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}