Molecular human reproduction最新文献_第4页

Beyond neurobiology: cellular prion protein (PRNP) as an emerging regulator of decidual and utero-placental vascular function. 超越神经生物学：细胞朊蛋白（PRNP）作为蜕膜和子宫胎盘血管功能的新兴调节因子。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag026

Rumela Bose Banerjee, Rupasri Ain

{"title":"Beyond neurobiology: cellular prion protein (PRNP) as an emerging regulator of decidual and utero-placental vascular function.","authors":"Rumela Bose Banerjee, Rupasri Ain","doi":"10.1093/molehr/gaag026","DOIUrl":"10.1093/molehr/gaag026","url":null,"abstract":"The establishment of a functional utero-placental interface depends on the precise temporal and spatial coordination of blastocyst attachment, decidual transformation, trophoblast invasion, and uterine spiral artery remodeling (SAR). Disruption of these tightly regulated processes underlies major placental pathologies, including preeclampsia, fetal growth restriction, and stillbirth. Although significant advances have been made in defining the molecular networks governing placental development, the contribution of cellular prion protein (PRNP) remains poorly characterized, warranting a focused review. Classically studied in the context of neurobiology and prion-associated neurodegenerative diseases, PRNP is now emerging as an important regulator of reproductive and vascular physiology. This review provides an overview of current evidence supporting non-neuronal roles of PRNP during early pregnancy, with particular emphasis on decidualization and utero-placental vascular adaptation. PRNP displays dynamic expression in the uterine glands, decidua, and vascular smooth muscle cells (VSMCs), where it contributes to tight-junction integrity, decidual cell survival, and autophagic homeostasis. Within the vascular compartment, PRNP regulates trophoblast-directed VSMC phenotypic switching by limiting proliferation, promoting platelet-derived growth factor-β-focal adhesion kinase-dependent migration, and protecting VSMCs from TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis, processes essential for effective SAR. Notably, PRNP expression is transcriptionally regulated by odd-skipped related transcription factor 1 (OSR1), which is itself negatively modulated by trophoblast cells. Collectively, these findings position PRNP beyond its traditional neurobiological role as a sensitive molecular indicator of decidual competence and vascular remodeling status, highlighting its potential as a biomarker and therapeutic target in placental disorders.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The post-reproductive ovary shifts from a reproductive to an immune-like organ. 生殖后的卵巢从生殖器官转变为免疫器官。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag038

Aubrey Converse, Shweta S Dipali, Ian P Schowe, Emmett B Kelly, Shivani S Jambunathan, Sarah R Ocañas, Michael B Stout, Michele T Pritchard, Francesca E Duncan

{"title":"The post-reproductive ovary shifts from a reproductive to an immune-like organ.","authors":"Aubrey Converse, Shweta S Dipali, Ian P Schowe, Emmett B Kelly, Shivani S Jambunathan, Sarah R Ocañas, Michael B Stout, Michele T Pritchard, Francesca E Duncan","doi":"10.1093/molehr/gaag038","DOIUrl":"10.1093/molehr/gaag038","url":null,"abstract":"Reproductive aging in females is characterized by the irreversible depletion of ovarian follicles, yet the structure and function of the post-reproductive ovary remain poorly defined. Using paired histological and bulk transcriptomic analyses of ovaries from reproductively young (2 m), reproductively old (18 m), and post-reproductive (24 m) mice, we mapped how ovarian identity evolves beyond follicle exhaustion. As expected, follicle loss, stromal remodeling, and increased collagen deposition were observed in the reproductively old and post-reproductive cohorts. Transcriptomic analyses revealed a shift from reproductive functionality to an immune-dominant signature with age. Correspondingly, post-reproductive ovaries exhibited increased infiltration of T cells, macrophages, and multinucleated giant cells. Although old and post-reproductive ovaries diverged substantially from young ovaries, they also showed discrete transcriptomic differences, indicating that the ovary continues to undergo molecular changes after reproductive senescence. Lastly, age-dependent changes in ovarian factors that are predicted to be secreted suggest that the post-reproductive ovary could be a source of pro-inflammatory signaling mediators with the potential to modulate extra-ovarian tissues. These findings challenge the assumption that the post-reproductive ovary is inert, instead indicating that it acquires an immune identity with potential endocrine and paracrine influence on whole-body aging.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13313162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Somatic mutations in endometrial epithelium: biological insights and emerging in vitro models. 子宫内膜上皮体细胞突变：生物学的见解和新兴的体外模型。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag027

Sugarniya Subramaniam, Caroline E Gargett, Harriet C Fitzgerald, Grant W Montgomery, Brett McKinnon

{"title":"Somatic mutations in endometrial epithelium: biological insights and emerging in vitro models.","authors":"Sugarniya Subramaniam, Caroline E Gargett, Harriet C Fitzgerald, Grant W Montgomery, Brett McKinnon","doi":"10.1093/molehr/gaag027","DOIUrl":"10.1093/molehr/gaag027","url":null,"abstract":"The human endometrium is a complex, dynamic, and poorly understood tissue involving monthly cyclical regeneration likely from adult stem/progenitor cells. This regeneration is associated with reproductive pathologies, such as endometriosis and adenomyosis. Endometrial epithelial cells have rates of mutations that are higher than expected for non-malignant tissue. Many of these mutations occur in known cancer-driver genes and can be inherited by endometriosis or adenomyosis lesions. The impact of these mutations on endometrial function and their contribution to endometrial pathologies is unclear. This gap in knowledge is partly due to the lack of suitable in vitro models for studying their effects on endometrial epithelial function. In this manuscript, we present a narrative review of the mutation landscape of the endometrium, their potential means of acquisition, and methods to study their consequences. Cataloguing and studying the role of somatic mutations will help us to understand their contribution to endometrial disease. Identifying their molecular and functional consequences will improve diagnostics, facilitate targeted treatment, and provide a step towards the personalization of treatment for endometrial pathologies.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Glycolytic reprogramming and MYH10 K1520 lactylation mediate eutopic endometrial collagen I deposition driven by PKM2-packaged ectopic endometrial extracellular vesicles. 糖酵解重编程和MYH10 K1520乳酸化介导由pkm2包装的异位子宫内膜细胞外囊泡驱动的异位子宫内膜I型胶原沉积。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag028

Liang Gao, Shiming Wang, Jingyu Zhang, Linhui Gao, Nannan Kang, Jidong Zhou, Jianjun Zhou

{"title":"Glycolytic reprogramming and MYH10 K1520 lactylation mediate eutopic endometrial collagen I deposition driven by PKM2-packaged ectopic endometrial extracellular vesicles.","authors":"Liang Gao, Shiming Wang, Jingyu Zhang, Linhui Gao, Nannan Kang, Jidong Zhou, Jianjun Zhou","doi":"10.1093/molehr/gaag028","DOIUrl":"10.1093/molehr/gaag028","url":null,"abstract":"Endometriosis (EMs) is characterized by ectopic lesions that disrupt endometrial decidualization, a process frequently accompanied by aberrant collagen deposition and closely linked to clinical infertility. Extracellular vesicles (EVs) are key mediators of intercellular communication and contribute to the pathogenesis and progression of EMs. However, whether EVs promote type I collagen deposition in the eutopic endometrium through glycolytic reprogramming and subsequent non-histone lactylation remains unclear. This study reveals that PKM2-carrying EVs derived from ectopic endometrial stromal cells (designated EMs-EVs) are transported via the systemic circulation to eutopic endometrial stromal cells and are internalized. This process upregulates PKM2 in the eutopic endometrium, triggering glycolytic reprogramming and lactate accumulation. The increased lactate level induces lactylation at lysine 1520 (K1520la) of myosin heavy chain 10 (MYH10). This modification not only upregulates α-smooth muscle actin (α-SMA) but also enhances the binding between MYH10 and α-SMA: an interaction essential for conferring contractile properties to stress fibers. Consequently, these events promote type I collagen deposition and contribute to defective decidualization in the eutopic endometrium. Collectively, our findings demonstrated that EMs-EVs drive endometrial collagen deposition through PKM2-mediated glycolytic reprogramming and subsequent MYH10 K1520 lactylation, thereby deepening our understanding of the role of impaired decidualization in the development of endometriosis-associated infertility.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exogenous putrescine supplementation improves cyclophosphamide-induced premature ovarian insufficiency in mice. 外源性腐胺补充改善环磷酰胺诱导的小鼠卵巢早衰。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag018

Chenxi Zhao, Cong Xu, Qian Zhang, Yuyi Wang, Siyuan Xie, Chao Gao, Yugui Cui, Wei Wu

{"title":"Exogenous putrescine supplementation improves cyclophosphamide-induced premature ovarian insufficiency in mice.","authors":"Chenxi Zhao, Cong Xu, Qian Zhang, Yuyi Wang, Siyuan Xie, Chao Gao, Yugui Cui, Wei Wu","doi":"10.1093/molehr/gaag018","DOIUrl":"10.1093/molehr/gaag018","url":null,"abstract":"The incidence of premature ovarian insufficiency (POI) is gradually increasing, and currently, no clinical treatments are available to restore ovarian function in POI patients, which severely affects the physical and mental health of young women with fertility needs. Putrescine is a type of polyamine found in the human body and different foods, and research has shown that adding putrescine to drinking water can reduce embryo resorption rates in aged mice. Polyamines are also closely related to apoptosis, with ovarian granulosa cell (GC) apoptosis considered an important factor in follicular atresia, which may lead to POI. Therefore, we investigated putrescine's actions in POI. We generated a drug-induced POI mouse model by intraperitoneally injecting cyclophosphamide (Cy) into animals. Putrescine was then added to their drinking water to explore its effects on ovarian function in mice. In vitro, we added 4-hydroxycyclophosphamide and putrescine to a GC line to examine the specific mechanisms underpinning putrescine actions. We discovered that putrescine improved ovarian function and fertility in Cy-induced POI mice and ameliorated GC apoptosis via P53 signaling. These findings provide potential therapeutic strategies for patients with POI.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The journey of maternal platelets through the utero-placental circulation: routes, interactions, and physiological implications. 母体血小板通过子宫-胎盘循环的旅程：路线，相互作用和生理意义。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag023

Désirée Forstner, Martin Gauster, Berthold Huppertz, Freya Lyssy

{"title":"The journey of maternal platelets through the utero-placental circulation: routes, interactions, and physiological implications.","authors":"Désirée Forstner, Martin Gauster, Berthold Huppertz, Freya Lyssy","doi":"10.1093/molehr/gaag023","DOIUrl":"10.1093/molehr/gaag023","url":null,"abstract":"Maternal platelets fulfil an exceptional and multifaceted plethora of roles during pregnancy, extending far beyond their traditional function in hemostasis. Increasing evidence suggests that platelets participate in placental development, immune modulation, and vascular adaptation at the maternal-fetal interface. This review traces the journey of maternal platelets from a possible adaptation of megakaryopoiesis in the maternal bone marrow to their first encounter with trophoblast cells during early placentation, continuing their way into the intervillous space and eventually leaving the utero-placental circulation, returning to maternal peripheral blood. Important hemodynamic changes during pregnancy, including a reduction in platelet count and an augmented uterine blood flow, will be highlighted. Initial contact of maternal platelets with invading extravillous trophoblasts at the sites of plugging of invaded spiral arteries is underscored, with further discussion of the influence on trophoblast behavior, vascular remodeling, and local inflammatory signaling. Furthermore, following the routes by which platelets access the intervillous space and interact with the syncytiotrophoblast, the dynamic exchange of soluble mediators, surface receptors, and extracellular vesicles is explored. The bidirectional nature of platelet-trophoblast communication is discussed, as are its potential implications for placental function in both physiological and pathological pregnancies. Finally, the possibility is addressed that platelets, following placental interaction, re-enter the maternal vasculature with altered phenotypic or functional properties. This review emphasizes the importance of maternal platelets as active regulators of placental biology and pregnancy outcome by synthesizing current insights.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13183671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of the lysophosphatidic acid-Lpar3 axis contributes to platelet-rich plasma-induced decidualization. 溶血磷脂酸- lpar3轴的激活有助于富血小板血浆诱导的去个体化。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag022

Tetsuaki Kaku, Shizu Aikawa, Kuniyuki Kano, Michiyo Okudaira, Yamato Fukui, Chihiro Ishizawa, Junken Aoki, Yasushi Hirota

{"title":"Activation of the lysophosphatidic acid-Lpar3 axis contributes to platelet-rich plasma-induced decidualization.","authors":"Tetsuaki Kaku, Shizu Aikawa, Kuniyuki Kano, Michiyo Okudaira, Yamato Fukui, Chihiro Ishizawa, Junken Aoki, Yasushi Hirota","doi":"10.1093/molehr/gaag022","DOIUrl":"10.1093/molehr/gaag022","url":null,"abstract":"Despite significant advancements in ARTs, nearly 70% of embryo transfers fail, with implantation failure being the primary cause. Proper embryo implantation requires coordinated communication between the blastocyst and a receptive endometrium, particularly through stromal cell decidualization. A thin or poorly responsive endometrium is associated with reduced implantation and pregnancy rates. However, effective treatments for enhancing endometrial receptivity remain limited. Platelet-rich plasma (PRP), which contains growth factors and bioactive molecules, has recently emerged as a promising agent for improving endometrial thickness and fertility outcomes in patients experiencing repeated implantation failures. However, the underlying molecular mechanisms remain unclear. In the present study, we investigated the effects of PRP on the uterus using a pseudopregnant mouse model that mimics the hormonal and endometrial conditions of early pregnancy. We found that intrauterine PRP injection induced decidual-like responses even in the absence of an embryo. Lipidomic analysis revealed that PRP contains high levels of lysophosphatidic acid (LPA), a signaling lipid that promotes decidualization via the G protein-coupled receptor Lpar3. In agreement with the lipidomic data, the injection of pure LPA also evoked decidual reactions. Notably, PRP-induced decidualization was abolished in Lpar3-deficient mice. These findings indicate that PRP exerts its pro-decidual effects through the LPA-Lpar3 axis and provide mechanistic insights into its therapeutic potential for improving implantation success.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Vaginal Escherichia coli infection impairs ovarian homeostasis: phenotypic characterization and mechanistic insights. 阴道大肠杆菌感染损害卵巢稳态：表型表征和机制的见解。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag029

Pingping Lin, Qianqian Lu, Xiaojing Hou, Jie Chen, Chen Yan, Aiwen Wu, Huimin Fan, Xinyan Wang, Zhen Zeng

{"title":"Vaginal Escherichia coli infection impairs ovarian homeostasis: phenotypic characterization and mechanistic insights.","authors":"Pingping Lin, Qianqian Lu, Xiaojing Hou, Jie Chen, Chen Yan, Aiwen Wu, Huimin Fan, Xinyan Wang, Zhen Zeng","doi":"10.1093/molehr/gaag029","DOIUrl":"10.1093/molehr/gaag029","url":null,"abstract":"Premature ovarian insufficiency (POI), a condition characterized by the loss of ovarian function before the age of 40, has emerged as a critical contributor to declining global fertility rates and the increasing prevalence of female infertility. Growing epidemiological evidence suggests that reproductive tract infections may represent a previously underappreciated risk factor for POI development, although the underlying mechanisms remain unclear. This study established a mouse model of chronic vaginal Escherichia coli (E. coli) infection to systematically investigate the potential impacts and underlying mechanisms of long-term vaginal E. coli infections on ovarian function, with particular focus on vaginal microbiota homeostasis and female reproductive health. Our study observed that long-term vaginal E. coli infection significantly impairs reproductive function of mice, manifesting as reduced fertility with diminished offspring production, concurrent with disrupted estrous cycle and impaired ovarian endocrine function. The infection caused significant ovarian reserve depletion, characterized by reduced primordial follicle counts accompanied by increased numbers of atretic follicles, as well as diminished follicular quality. Mechanistically, over-activation of the PI3K-mTORC signaling pathway was identified as a key driver of primordial follicle pool exhaustion, thereby accelerating ovarian reserve decline. These findings establish chronic reproductive tract infections as a modifiable risk factor for ovarian dysfunction, highlighting the importance of infection screening in fertility preservation strategies and paving the way for future research into microbiota-based interventions for maintaining ovarian health.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of changes in fat metabolism by particulate matter on endometrium and infertility. 颗粒物质脂肪代谢变化对子宫内膜和不孕症的影响。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag034

Gee Soo Jung, Inha Lee, Hyunho Koo, Min Jung Lee, Wooseok Im, Hyemin Park, Jae Hoon Lee, SiHyun Cho, Young Sik Choi

{"title":"Effects of changes in fat metabolism by particulate matter on endometrium and infertility.","authors":"Gee Soo Jung, Inha Lee, Hyunho Koo, Min Jung Lee, Wooseok Im, Hyemin Park, Jae Hoon Lee, SiHyun Cho, Young Sik Choi","doi":"10.1093/molehr/gaag034","DOIUrl":"10.1093/molehr/gaag034","url":null,"abstract":"Particulate matter (PM) exposure has been increasingly linked to metabolic and reproductive disorders, yet the mechanisms through which PM-related metabolic alterations influence endometrial function remain incompletely understood. In this study, female C57BL/6 mice were fed a normocaloric diet or high-fat diet (HFD) with or without PM exposure for 12 weeks. Body weight, fertility outcomes, and molecular alterations were assessed in visceral adipose tissue (VAT) and endometrial tissue (EMT). In parallel, 3T3-L1 adipocytes were co-cultured with primary human endometrial cells to examine adipocyte-endometrial interactions in vitro. PM exposure was associated with attenuated overall weight gain but increased visceral adiposity and reduced fertility, particularly under HFD conditions. In both VAT and EMT, PM exposure was accompanied by increased expression of pro-inflammatory cytokines and elevated levels of p-NF-κB and p-c-jun. Alterations in adipokine profiles were observed, characterized by increased leptin and decreased adiponectin expression with PM exposure, particularly after the HFD. Hormone receptor expression displayed tissue-specific patterns, with higher AR and ER-α/ER-β ratios in VAT and opposite trends in EMT. Markers of cellular stress and apoptosis were also elevated in PM-exposed groups. In the co-culture model, PM exposure was associated with increased levels of p-Nrf2, p-ERK, and p-p38, together with altered leptin and adiponectin expression levels. Taken together, these findings suggest that PM exposure, particularly in the context of diet-induced obesity, may be associated with dysregulation of the adipose-endometrial crosstalk involving inflammation, oxidative stress-related signaling, and hormonal imbalance, which could contribute to adverse reproductive outcomes.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-induced miR-21-5p promotes autophagy by downregulating CDC25A in endometriosis. 缺氧诱导的miR-21-5p通过下调CDC25A在子宫内膜异位症中促进自噬。

IF 4.2 2区医学

Molecular human reproduction Pub Date : 2026-04-11 DOI: 10.1093/molehr/gaag020

Huan-Tzu Hou, Ya-Chuan Tsai, Shih-Chieh Lin, Po-Hung Pan, Meng-Hsing Wu, Shaw-Jenq Tsai

{"title":"Hypoxia-induced miR-21-5p promotes autophagy by downregulating CDC25A in endometriosis.","authors":"Huan-Tzu Hou, Ya-Chuan Tsai, Shih-Chieh Lin, Po-Hung Pan, Meng-Hsing Wu, Shaw-Jenq Tsai","doi":"10.1093/molehr/gaag020","DOIUrl":"10.1093/molehr/gaag020","url":null,"abstract":"Endometriosis is a common gynecological disorder affecting women of reproductive age, often leading to chronic pain, reduced quality of life, and infertility. It is characterized by ectopic endometrial growth within a hypoxic peritoneal environment. Autophagy, a cellular recycling pathway, is elevated in ectopic lesions. However, how hypoxia regulates autophagy to drive lesion development remains unclear. We found that inhibition of autophagy with chloroquine reduced stromal cell growth under hypoxia. The microRNA miR-21-5p, previously shown to be elevated by hypoxia in ectopic lesions, was examined and found to target cell division cycle 25A (CDC25A). Overexpression of miR-21-5p suppressed CDC25A. Under hypoxia, yes-associated protein 1 (YAP1) nuclear accumulation increased miR-21-5p, which in turn further reduced CDC25A expression. Silencing CDC25A enhanced autophagic flux, whereas pharmacologic inhibition of YAP1 with verteporfin restored CDC25A and p62 in mouse lesions and reduced lesion size. Collectively, these findings demonstrate that hypoxia activates YAP1-driven miR-21-5p, which represses CDC25A to promote autophagy and sustain lesion survival, highlighting the miR-21-5p/CDC25A axis as a potential therapeutic target.","PeriodicalId":18759,"journal":{"name":"Molecular human reproduction","volume":" ","pages":""},"PeriodicalIF":4.2,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0