Placental CD4+ T Cells from Preeclamptic patients with a history of COVID-19 cause long term maternal cardiovascular consequences and cognitive dysfunction in offspring

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with activated CD4+ T cells, altered cerebral blood autoregulation, and impaired neurological dysfunction. Additionally, a history (Hx) of COVID-19 (CV) infection during pregnancy is associated with an increased incidence of a PE and prolonged neurological symptoms. We have previously shown that adoptive transfer of CD4+ T cells from PE patients with and without a Hx of CV causes hypertension, increased inflammation, and impaired neurological function during pregnancy. In addition, we have shown that treatment with etanercept (ETAN) decreases hypertension (HTN) in RUPP rat model of PE, however the effect of TNF-alpha blockade on neurological function during PE with or without a history (Hx) of CV infection is unknown. Therefore, we sought to examine a role for Etanercept to improve neurological and cardiovascular outcomes in postpartum (PP) recipient rats of CD4+ T cells from PE placentas with or without a CV history (Hx). A second objective was to determine if perinatal Etan improved blood pressure and neurovascular function in the offspring. One million placental CD4+ T cells from PE and normotensive (NT) patients with or without a CV Hx during pregnancy were injected i.p. into gestational day (GD) 12 nude athymic rats. ETAN was administered i.p. on day 18. HTN and neurological function was examined at 12 weeks PP in dams and 16 weeks in the offspring. Cerebral Blood Flow (CBF) was measured in dams by Doppler flowmetry and carotid catheters were placed in offspring at 16 weeks for blood pressure measurements. Neurological function was assessed by behavioral tests (Barnes maze and novel object recognition). A two-way ANOVA was used for statistical analysis. MAP remained elevated 12 weeks PP in PE CV Hx (153 mmHg±6, n=7) and PE (150±5 mmHg, n=5, p<0.05) compared to NT CV Hx (121±6 mmHg, n=6) and NP (116±6 mmHg, n=6). MAP was not significantly attenuated in PP PE CV Hx+ETAN (136 mmHg±11, n=3) or PP PE+ETAN (143±9 mmHg, n=6). At 12 weeks PP, PE and CV Hx PE had impaired autoregulation and memory compared to either NP or NT CV Hx control groups, which was not improved with Etan. At 16 weeks, there were no significant changes in MAP in female or male offspring. Behavior tests in the offspring indicated a decrease in memory and learning in the Barnes maze by PE CV Hx male and female offspring compared to NT CV Hx or NP controls. Etan improved memory and cognition only in female offspring of PE CV Hx. CD4+ T cells from PE women with or without a CV Hx during pregnancy cause maternal cardiovascular and cognitive dysfunction in PP dams which was not improved with Etanercept. However, TNF alpha blockade did exhibit a sex difference to improve female offspring cognitive function. Therefore, perinatal TNF alpha. NIH grants RO1HD067541-06 (BL), P20GM121334 (BL,LMA), AHA 19CDA34670055 (LMA), and T32 Trainee Grant T32-HL105324 (ED). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.