Frontiers in immunology · 2026
Fetal sex shapes maternal immune adaptation: placental extracellular vesicles differentially reprogram the phenotype, metabolism, and function of circulating monocytes.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Avalos Julieta, Sabbione Florencia, Rios Daiana, Grasso Daniel H, Garcia M Noe, Aguilera Franco, Merech Fatima, Aiello Horacio, Meller Cesar, Ramhorst Rosanna, Hauk Vanesa, Gori Soledad, Leirós Claudia Pérez, Vota Daiana M, Paparini Daniel E
Аннотация
INTRODUCTION: 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.
METHODS: 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.
RESULTS: 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-1β 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.
DISCUSSION: 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.
METHODS: 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.
RESULTS: 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-1β 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.
DISCUSSION: 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.