S4 - Symposium 2

Let's talk about sex: Contribution of placental extracellular vesicles during pregnancy.

Avalos, Julieta ¹ - Aguilar, Franco ^1,2 - Grasso, Daniel ³ - García M. Noé ³ - Sabbione, Florencia ⁴ - Charó, Nancy ⁴ - Lara, Brenda ¹ - Hauk, Vanesa ¹ - Meller, Cesar ⁵ - Aiello, Horacio ⁵ - Martí, Marcelo A. ² - Ramhorst, Rosanna ¹ - Grasso, Esteban ¹ - Pérez Leirós, Claudia ¹ - Vota, Daiana M. ¹ - Paparini, Daniel E.* ¹

1) Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET), Laboratorio de Inmunofarmacologia, Buenos Aires, Argentina
2) Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN-CONICET), Laboratorio de Bioinformática, Buenos Aires, Argentina
3) Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-Universidad de Buenos Aires, Junín 956, Piso
4, Buenos Aires CP 1113, Argentina.
4) Instituto de medicina experimental (IMEX)-CONICET/Academia Nacional de Medicina de Buenos Aires, Buenos Aires, Argentina.
5) Hospital Italiano de Buenos Aires, Servicio de Obstetricia, Buenos Aires, Argentina
Contacto: daniel.paparini@gmail.com

For years, differences in the immune system between men and women have been reported, partly due to genetic and hormonal effects. Pregnancy is a unique time when at least two individuals of different sexes can coexist and interact with each other, partly through extracellular vesicles (EVs). In this study, we investigated the role of placental EVs (pEVs) in endothelial cell (EC) function and the activation and metabolic profile of macrophages (MA), depending on the sex of the newborn.
pEVs were isolated from the conditioned media (CM) of placental villi explant by differential centrifugation and characterised. Monocytes from healthy female donors’ peripheral blood were differentiated into MA with GM-CSF and then cultured with CM or EVs from male (M) or female (F) placentas, in order to assess their phenotypic and metabolic profile using flow cytometry. HBC were obtained from normal term placenta by enzymatic digestion, and CM were used to study angiogenesis. HUVEC were used to study endothelial cell migration.
CM from female placentas (F-CM) polarised MA towards a stronger antiinflammatory phenotype, increasing the expression of CD163, CD206, CD209 and IL-10 secretion by almost twofold respect to male placentas (M-CM, P<0.05). Only F-CM increased lipid droplet accumulation (P<0.05), without altering glucose uptake or lactate secretion. Similar results were observed with F-pEVs. Furthermore, only F-pEVs increased endothelial cell migration (P<0.05). In line with this, F-CM from HBC exhibited a higher pro-migratory capacity than M-CM (P<0.05). Our results suggest that placental EVs play a differential regulatory role in macrophage phenotype and metabolism, aligning with the immunometabolic profile of HBC according to fetal sex. Additionally, these findings imply a potential involvement of sex-specific role for pEVs in endothelial cell function.