Abstract P200: Tnf-α Blockade During Pregnancy Does Not Impact Offspring Development In A Rat Model Of Preeclampsia

Preeclampsia (PE), new onset hypertension during pregnancy, is associated with increased tumor necrosis factor alpha (TNF-α), agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA), and low birth weight babies. We have previously shown that Etanercept ( E ), a TNF-α inhibitor, improves PE features in the reduced uterine perfusion pressure (RUPP) rat. However, the long-term effect of E on offspring health and immune competency has not been studied. Therefore, we hypothesize that E will improve maternal health without affecting offspring outcomes in a rat model of PE. To test this hypothesis, E (0.4 mg/kg) was injected on gestation day 18 into sham and RUPP dams which were allowed to deliver. Weights were recorded at birth and 16 weeks of age when mean arterial pressure (MAP) was measured. Whole blood was collected to measure immune cells by flow cytometry. AT1-AA was measured using a cardiomyocyte bioassay. A student’s t-test was used to compare differences among male and female RUPP offspring with and without E . RUPP male and female offspring were smaller (5.21±0.19 g, n=7; 5.24±0.10 g, n=7) than sham offspring (5.94±0.14 g, n=7, p<0.05; 5.86±0.16 g, n=9, p<0.01) while RUPP male offspring were larger and female offspring were unchanged following perinatal E (6.01±0.29 g, n=9, p<0.05; 5.28±0.14, n=9). MAP was comparable between sham (133±4 mmHg) and RUPP (132±4 mmHg) male offspring with no change seen following perinatal E (133±4 mmHg). Perinatal E did not impact adult male circulating B cells. Circulating AT1-AA was elevated in male RUPP offspring (16±2 ΔBPM, p<0.01) compared to sham and was not improved with E (13±2 ΔBPM). MAP was comparable in sham (131±5 mmHg) and RUPP (130±5 mmHg) female offspring but trended downward with perinatal E (123±4 mmHg). RUPP female offspring had reduced circulating B cells (4.24±0.81 % gated, p=0.066) compared to sham females (9.56±2.07 % gated) which was normalized following perinatal E (9.04±1.42 % gated, p<0.05). AT1-AA trended lower following perinatal E (7±2 ΔBPM, p=0.0888) compared to RUPP female offspring (16±3 ΔBPM). Our findings indicate that E does not worsen fetal outcomes. Moreover, E improves male birth weight and reduces adult female AT1-AA without compromising offspring immune competency.