897 Maternal obesity and male offspring sex are associated with altered hofbauer cells

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Placental Hofbauer cells (HC) are resident tissue macrophages of fetal origin that play an important role in placental function and fetal immune protection and vulnerability. Maternal infections and metabolic challenges can alter the number and/or activation state of HCs. Associations between HCs and maternal and fetal characteristics remain unclear. We sought to quantify HC density and activation state to determine whether these characteristics were associated with maternal obesity and fetal sex. This is a cross-sectional study of 27 women undergoing planned cesarean delivery at term; women with hypertension or diabetes were excluded. Maternal first trimester body mass index (BMI) and fetal sex were obtained by chart review. Immunohistochemistry was performed on serial placental sections for CD163 (M2 macrophage marker) and CD68 (M1 marker, expressed by only a subset of HCs). Numbers of CD163+ and CD68+ cells per mm2 of villous area were quantified in terminal villi using ImageJ software. Quantification was performed on ten 20x images per section. Relationships between maternal obesity, fetal sex, and HC density were determined using 2-way ANOVA, with Tukey’s post hoc test to determine source of differences. 41% of patients were obese (BMI ≥ 30 kg/m2 in first trimester) and 44% had male newborns. Mean density of CD163+ HCs was greater than CD68+ HCs (mean±SD: 374±79 vs 310±64 cells/mm2, t-test, P=0.002). CD163+ HC density varied significantly by maternal obesity and fetal sex (2-way ANOVA, sex/obesity interaction P=0.04). CD163+ HC density was significantly greater in obese pregnancy, and this difference was driven disproportionately by male offspring (P=0.02, 1A). While number of CD68+ HCs did not vary by maternal obesity or fetal sex (1B), the ratio of CD163/CD68 HCs did vary significantly by fetal sex (1C, P=0.02). Maternal obesity is associated with a significant increase in CD163+ HCs, with males primarily driving this difference. Increased CD163:CD68 ratio may indicate a switch to M2 HC phenotype in males in response to maternal obesity.