{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:10:16Z","timestamp":1784268616707,"version":"3.55.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Maternal immune adaptation during pregnancy is orchestrated by dynamic signals from the uterine microenvironment, including placental extracellular vesicles (pEVs) released into maternal circulation. EVs have emerged as key mediators of this crosstalk; however, their role in sex-specific immune modulation remains incompletely defined. Here, we investigated whether pEVs derived from term placentas induce sex-dependent changes in the phenotype, metabolism, and function of human monocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>pEVs were isolated from 13 term uncomplicated placentas (six male-derived, M-pEVs, and seven female-derived, F-pEVs) and characterized by complementary approaches, revealing similar size distributions and concentrations, with differences in physicochemical properties and molecular cargo. Circulating monocytes from 17 non-pregnant female donors were exposed to M-pEVs or F-pEVs and analyzed for phenotypic, metabolic, and functional responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>pEVs induced distinct activation profiles depending on fetal sex. F-pEVs reduced CD11b and CD11c expression while increasing CD14, CD39 and IL-10 production. On the other hand, M-pEVs increased CD14 expression and enhanced IL-1\u03b2 secretion. Both nanovesicles populations increased IL-10 and CXCL8 release and promoted a shift toward classical monocytes (CD14+CD16-) with a reduction in the intermediate subsets. Metabolic analyses revealed divergent immunometabolic programs: M-pEVs promoted lactate and reactive oxygen species production, whereas F-pEVs enhanced lactate production, fatty acid uptake, lipid droplet accumulation, and mitochondrial activity without increasing ROS. Functionally, both pEV populations increased efferocytosis, with a distinct sensitivity to metabolic inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that pEVs differentially modulate circulating monocytes according to fetal sex and support a role for fetal sex in shaping maternal immunometabolic responses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1855111","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T05:43:25Z","timestamp":1784267005000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fetal sex shapes maternal immune adaptation: placental extracellular vesicles differentially reprogram the phenotype, metabolism, and function of circulating monocytes"],"prefix":"10.3389","volume":"17","author":[{"given":"Julieta","family":"Avalos","sequence":"first","affiliation":[{"name":"Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET), Laboratory of Immunopharmacology, Facultad de Ciencias Exactas y Naturales (FCEN-UBA)","place":["Buenos Aires, Argentina"]},{"name":"Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales (FCEN-UBA). Departamento de Qu\u00edmica Biol\u00f3gica","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florencia","family":"Sabbione","sequence":"additional","affiliation":[{"name":"Instituto de medicina experimental (IMEX)-CONICET\/Academia Nacional de Medicina de Buenos Aires","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiana","family":"Rios","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales (FCEN-UBA). Departamento de Qu\u00edmica Biol\u00f3gica","place":["Buenos Aires, Argentina"]},{"name":"Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET). Laboratory of Immunomodulation, Metabolism and Cell communication, Facultad de Ciencias Exactas y Naturales (FCEN-UBA)","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H.","family":"Grasso","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Pharmacy and Biochemistry, University of Buenos Aires","place":["Buenos Aires, Argentina"]},{"name":"Institute of Humoral Immunity Studies (IDEHU), CONICET, Faculty of Pharmacy and Biochemistry, University of Buenos Aires","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Noe","family":"Garcia","sequence":"additional","affiliation":[{"name":"Institute of Humoral Immunity Studies (IDEHU), CONICET, Faculty of Pharmacy and Biochemistry, University of Buenos Aires","place":["Buenos Aires, Argentina"]},{"name":"Chair of Immunology, Department of Microbiology, Immunology, Biotechnology and Genetics, Faculty of Pharmacy and Biochemistry, University of Buenos Aires","place":["Buenos Aires, Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Instituto de Qu\u00edmica Biol\u00f3gica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET), Laboratory of Immunopharmacology, Facultad de Ciencias Exactas y Naturales (FCEN-UBA)","place":["Buenos Aires, Argentina"]},{"name":"Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales (FCEN-UBA). 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