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

Abstract

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 Foxp3^DTR 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 causes defective decidual uterine spiral artery remodeling, uterine artery dysfunction, elevated fetal loss, and fetal growth restriction. Maternal Treg cell deficiency led to marked alterations in cardiac adaptations at 4-7 wk postpartum, including reduced left ventricular mass ([Formula: see text]29% end-diastolic and systolic left ventricular mass; both P ≤ 0.024), decreased aortic diameter ([Formula: see text]12%; P = 0.004), and increased fractional shortening ([Formula: see text]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 ([Formula: see text]40%; P = 0.001) and reduced kidney, uterine, and brain weights ([Formula: see text]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.NEW & NOTEWORTHY In this study, we show that maternal Treg cell deficiency in early pregnancy leads to altered maternal cardiac structure and organ homeostasis in the early postpartum period. These findings imply that in addition to regulating pregnancy immune and vascular adaptation, Treg cells are also critical for maternal postpartum cardiovascular recovery.