{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T20:05:04Z","timestamp":1771445104091,"version":"3.50.1"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Increasing evidence suggests that the biological activity of trophoblasts and M1-type macrophages plays a crucial role in recurrent spontaneous abortion. However, detailed mechanistic studies on the intercellular communication between these two cells at the maternal-fetal interface are not clear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, extracellular vesicles (EVs) were first isolated from the supernatant of M1 macrophages induced by THP-1 cells (M1-EVs), identified by transmission electron microscopy, exosome immunofluorescence uptake, and western blotting, and characterized by mRNA sequencing to screen for specific target genes by mRNA profiling. CCK8 and western blotting experiments were used to investigate the effects of M1-EVs on trophoblast proliferation and autophagy. Subsequently, target genes MPPED2 and PI3K\/AKT signaling pathway were found by bioinformatics analysis of raw mRNA sequencing results. Western blotting and CCK8 experiments were used to reveal the potential mechanisms by which MPPED2 in M1-EVs regulates trophoblast function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>M1 macrophages induce inflammatory responses in the mother and fetus, and M1 macrophages inhibit trophoblast autophagy and proliferative capacity by secreting EVs. By mRNA transcriptome sequencing, MPPED2, among others, were identified as the most up-regulated mRNAs in M1-EVs-treated trophoblasts. Further functional experiments indicate that M1 macrophage-derived exosomes may regulate PI3K\/AKT pathway activity by transferring MPPED2, leading to reduced autophagy and proliferation activity in trophoblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that MPPED2 from exosomes plays an important role in intercellular communication between M1 macrophages and the trophoblast, elucidating a novel mechanism by which M1 macrophages regulate trophoblast function and its role in recurrent spontaneous abortion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/biolre\/ioaf249","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T12:26:17Z","timestamp":1762777577000},"page":"647-661","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular vesicles derived from M1 macrophages deliver MPPED2 and regulate PI3K\/AKT to suppress trophoblast autophagy and proliferation in recurrent spontaneous abortion"],"prefix":"10.1093","volume":"114","author":[{"given":"Cen","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chongqing Key Laboratory of Maternal and Fetal Medicine\/Joint International Research Laboratory of Reproduction & Development, Ministry of Education\/The Innovation and Talent Recruitment Base of Maternal-Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University , No.1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-7942","authenticated-orcid":false,"given":"Hongbo","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chongqing Key Laboratory of Maternal and Fetal Medicine\/Joint International Research Laboratory of Reproduction & Development, Ministry of Education\/The Innovation and Talent Recruitment Base of Maternal-Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University , No.1 Youyi Road, Yuzhong District, Chongqing 400016 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"2026021814241248400_ref1","doi-asserted-by":"publisher","first-page":"117082","DOI":"10.1016\/j.biopha.2024.117082","article-title":"Immunologic insights in recurrent spontaneous abortion: molecular mechanisms and therapeutic interventions","volume":"177","author":"Guan","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"2026021814241248400_ref2","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.fertnstert.2023.08.952","article-title":"Genetic causes of sporadic and recurrent miscarriage","volume":"120","author":"Melo","year":"2023","journal-title":"Fertil Steril"},{"key":"2026021814241248400_ref3","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/1741-7015-11-154","article-title":"New insights into mechanisms behind miscarriage","volume":"11","author":"Larsen","year":"2013","journal-title":"BMC Med"},{"key":"2026021814241248400_ref4","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1093\/humupd\/dmaa017","article-title":"Investigation of human trophoblast invasion in vitro","volume":"26","author":"Abbas","year":"2020","journal-title":"Hum Reprod Update"},{"key":"2026021814241248400_ref5","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41586-023-05869-0","article-title":"Spatial multiomics map of trophoblast development in early pregnancy","volume":"616","author":"Arutyunyan","year":"2023","journal-title":"Nature"},{"key":"2026021814241248400_ref6","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1007\/s10565-021-09687-w","article-title":"Lnc-HZ05 regulates BPDE-inhibited human trophoblast cell proliferation and affects the occurrence of miscarriage by directly binding with miR-hz05","volume":"38","author":"Mi","year":"2022","journal-title":"Cell Biol Toxicol"},{"key":"2026021814241248400_ref7","doi-asserted-by":"publisher","first-page":"1327167","DOI":"10.3389\/fcell.2024.1327167","article-title":"When autophagy meets placenta development and pregnancy complications. 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