{"title":"Characteristics of Exosomes and Microbiota in the Decidua of Patients With Early Pregnancy Loss and Their Impact on Trophoblast Cells","authors":"Fengping He, Lujing Chen, Jiwu Lou, Yanle Guo, Shushu Fan, Tizhen Yan, Yongmei Zhang","doi":"10.1002/mrd.70104","DOIUrl":"10.1002/mrd.70104","url":null,"abstract":"<p>Early pregnancy loss (EPL) is a common complication with incompletely understood pathogenesis. Recent studies highlight the roles of exosomes and their miRNAs in intercellular communication, and the influence of uterine decidual microbiota on pregnancy outcomes. This study aimed to characterize decidual exosomes and microbiota in EPL patients and explore their mechanistic roles in EPL development. Exosomes were extracted from decidual tissues of women undergoing normal pregnancy termination (NC group) and those with early pregnancy embryonic loss (EPL group). These exosomes were applied to treat trophoblast cells (HTR8/SVneo), and cell functions were examined using CCK-8, Transwell assays, and Annexin V-PI staining. Inflammation-related gene expression was quantified by qRT-PCR. Microarray analysis identified differentially expressed exosomal miRNAs, validated by qRT-PCR. 16S rRNA sequencing analyzed microbial community differences between groups, with key taxa identified using LEfSe. The roles of miR-483-5p mimics on <i>Lactobacillales</i> and trophoblast cells were also examined. Exosomes from both groups expressed CD63, HSP70, and Histone-H3, with typical membrane structures observed and particle sizes of 100-120 nm. Exosomes from the EPL group remarkably repressed trophoblast cell proliferation, migration, and invasion, promoted apoptosis, and upregulated TLR4, NF-κB, IL-6, TNF-α, and IL-8 mRNA levels. Microarray analysis revealed significant downregulation of miR-483-5p in exosomes from the EPL group. 16S rRNA sequencing showed distinct microbial communities in decidual tissues of the EPL group, particularly in <i>Lactobacillales</i> and <i>Erysipelotrichaceae</i> abundance. Hsa-miR-483-5p mimics enhanced <i>Lactobacillales</i> viability and colocalized with them. Combined treatment with miR-483-5p mimics and <i>Lactobacillales</i> reversed the inhibitory effects of exosomes from the EPL group on trophoblast cells and downregulated inflammatory factor expression. This study characterized exosomes in the decidual tissues of the EPL group and their inhibitory effects on trophoblast cells, identifying key miRNAs (miR-483-5p) and microbial taxa (<i>Lactobacillales</i>). These results indicate that exosomes and microbiota could play a role in EPL development by regulating trophoblast functions and inflammatory responses.</p>","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Suocheng, Xu Linglong, Gao Jingshuang, Guo Zhenya, Cai Yuan
{"title":"Kisspeptin-10 Promotes Hormone Secretion, Ovarian Follicles Development and Fecundity via PI3K/AKT/ERK Signal Pathway in Mice","authors":"Wei Suocheng, Xu Linglong, Gao Jingshuang, Guo Zhenya, Cai Yuan","doi":"10.1002/mrd.70093","DOIUrl":"10.1002/mrd.70093","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The present study aimed to comprehensively elucidate how KP-10 modulates hormone secretion, the proliferation and autophagy of ovarian follicles by regulating in-vivo and in-vitro levels of associated genes and proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Follicular granulosa cells (FGCs) were cultured in EMDM/F12 medium. The proliferation viability, apoptosis, and autophagy rates of FGCs were determined, respectively. For in-vivo tests, 0, 5, 10, 20, 40 μg/g of KP-10 were injected into 75 mice allocated into control group (CG) and four KP-10 treated groups (including KP-1, KP-2, KP-3, and KP-4 groups). Maximum transverse diameter (MTD), maximum longitudinal diameter (MLD) and follicle-wall thickness (FWT) of secondary follicles were measured in days 0, 5, 10, 15, and 25. RT-qPCR and Western blot were employed to determine the contents of genes and proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The KP-10-treated groups exhibited increased FGCs proliferation, accompanied by decreased apoptosis and autophagy rates as compared with the control group (CG). The expression levels of KISS1R, Bcl-2, LC3-II, mTOR, p62/Sqstm1, PI3K, AKT, and ERK genes and proteins in FGCs were significantly enhanced (<i>p</i> < 0.05). Additionally, the number of secondary follicles, MTD, MLD, FWT, and the serum concentrations of progesterone and estradiol were notably elevated (<i>p</i> < 0.05). Moreover, the in-vivo levels of PI3K, AKT, ERK mRNAs, as well as StAR and CYP11A1 genes and proteins, were significantly higher than those in CG. FGCs proliferation in KP-10-treated groups was increased with reduction of apoptosis and autophagy rates. Levels of KISS1R, Bcl-2, LC3-Ⅱ, mTOR, p62/Sqstm1, PI3K, AKT and ERK genes and proteins in FGCs were enhanced (<i>p</i> < 0.05). Numbers of the secondary follicles, MTD, MLD, FWT and serum concentrations of progesterone and estradiol were significantly promoted (<i>p</i> < 0.05). In-vivo levels of PI3K, AKT, ERK mRNAs, StAR and CYP11A1 genes and proteins were accelerated as compared to CG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>KP-10 accelerated the proliferation and suppressed the apoptosis and autophagy of FGCs, facilitated the development of the secondary follicles, and nd enhanced the synthesis and secretion of P4 and E2. Ten microgram per gram KP-10 had the best efficacy. Our study first time explored comprehensively the effects and mechanisms KP-10 in-vitro and in-vivo regulating reproductive hormone secretion, ovarian follicles development and fecundity in mice. These effects of KP-10 were achieved probably by activation of PI3K/AK","PeriodicalId":18856,"journal":{"name":"Molecular Reproduction and Development","volume":"93 4","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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