Postpartum cardiac structure and organ homeostasis following regulatory T cell depletion in early pregnancy.

Maternal insufficiency in regulatory T (Treg) cells in pregnancy impairs maternal-fetal immune tolerance and uteroplacental vascular adaptation. Whether Treg cell insufficiency in pregnancy has maternal postpartum consequences is unknown. Using Foxp3DTR mice, wherein diphtheria toxin (DT) is given to selectively deplete Foxp3+ Treg cells, we investigated whether early pregnancy Treg cell deficiency alters postpartum cardiometabolic outcomes. Transient Treg cell depletion was elicited by DT administration on gestational days 3.5 and 5.5, a protocol that causesdefective decidual uterine spiral artery remodelling, uterine artery dysfunction, elevated fetal loss, and fetal growth restriction. Maternal Treg cell deficiency led to marked alterations in cardiac adaptations at 4-7 weeks postpartum, including reduced left ventricular mass (↓29% end-diastolic and systolic left ventricular mass; both P≤0.024), decreased aortic diameter (↓12%; P=0.004), and increased fractional shortening (↑34%; P=0.042). Constriction responses in the mesenteric arteries and aortae were unchanged. Metabolic parameters and blood pressure were unaffected; however, DT-treated dams exhibited persistent splenomegaly (↑40%; P=0.001) and reduced kidney, uterine, and brain weights (↓7-40%; all P≤0.028). These findings demonstrate that Treg cell insufficiency in pregnancy alters maternal postpartum cardiac structure and organ homeostasis and supports investigation of Treg cell-targeted strategies to improve long-term maternal health.