Estrogen regulates placental immune processes in non-human primates†

The placenta is a crucial organ for sustaining pregnancy through nutrient exchange, hormone production, and immune modulation. Estrogen is an important modulator of immune function in pregnancy. This study investigates estrogen's effect on placental immune cell expression and whether there are sex-specific differences in an established non-human primate model of estrogen depletion. Pregnant baboons were assigned to three groups: untreated (n = 8), treated with the aromatase inhibitor letrozole (n = 8, 115 μg/kg/day) from days 100 to 165 of gestation, and treated with letrozole plus estradiol benzoate (n = 8, 25 -115 μg/kg/day). On days 165-175, placentas were obtained, and fetal and placental weights were recorded. Immunohistochemical staining was used to evaluate markers associated with the innate and adaptive immune systems in the placenta. Placental weight increased by 24.07% (P < 0.05) in the letrozole group. Fetal-to-placental weight ratio decreased by 15.54% (P < 0.05) in letrozole-treated. IBA-1 positive Hofbauer cell expression increased by 81.01% (P < 0.05) in letrozole-treated baboons, with a 61.40% reduction following estradiol treatment (P < 0.05), with a more significant effect observed in female fetuses (P < 0.05). Confirmatory staining of CD68+ Hofbauer cell expression rose by 74.4% (P < 0.05) in the letrozole group and decreased by 51.8% (P < 0.05) with estradiol treatment, with more pronounced effects in females. No significant changes were observed in the CD3 + CD4+ T-helper cells and CD8+ cytotoxic cells. These findings highlight estrogen's vital role in regulating placental immune profile, emphasizing its importance for optimal fetal development.