Prenatal Exposure to Endocrine Disruptors Followed By Adult Exposure to Estradiol-17 Beta Increases Blood Pressure in Female Rats
Presentation Number: OR15-6
Date of Presentation: April 1st, 2017
Sheba M J MohanKumar*1, Coral K Hahn-Townsend1, Hannah A Garver2, Joseph E Henriquez2, Gregory D Fink2 and Puliyur S MohanKumar1
1University of Georgia, Athens, GA, 2Michigan State University, E. Lansing, MI
Pregnant women are frequently exposed to endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) and diethyl hexyl phthalate (DEHP) and these chemicals are known to cross the placental barrier and "program" the fetus for adult disorders such as hypertension. When programmed female offspring are exposed to estrogenic compounds in adulthood (as in oral contraceptives), we hypothesize that it will hasten the onset and exacerbate the increase in blood pressure. These effects are most likely mediated through oxidative-stress related pathways in the brain. To test this hypothesis, we used pregnant Sprague Dawley rats and dosed them orally with vehicle, 5 µg/kg BW of BPA, 7.5 mg/kg BW of DEHP or a combination of both (B+D) from day 6-21 of gestation. Female offspring were allowed to reach 3 months of age and were implanted with a radio telemeter and also received an estradiol pellet capable of releasing 20 ng of estradiol 17ß (E2) per day for 90 days. Blood pressure changes were monitored for 90 days and the animals were sacrificed. The brain stem was sectioned and the rostral ventrolateral medulla (RVLM) was microdissected and analyzed for superoxide dismutase (SOD) activity. Treatment with E2 in adulthood increased average diastolic blood pressure (DBP) and mean arterial pressure (MAP). Prenatal exposure to EDCs in combination with E2 exposure in adulthood increased average systolic (SBP), DBP and MAP. Prenatal exposure to the combination of BPA and DEHP produced the most marked increase in blood pressure profiles. Analysis of the RVLM revealed that SOD activity decreased significantly with adult E2 exposures. Moreover, prenatal exposure to EDCs followed by adult exposure to E2 produced even further reductions in SOD activity. Since SOD is involved in scavenging free radicals, a reduction in SOD activity would indicate an increase in oxidative stress. These data suggest that prenatal EDC exposure could possibly increase the risk for development of hypertension most probably through oxidative stress related mechanisms in the brain.
Nothing to Disclose: SMJM, CKH, HAG, JEH, GDF, PSM