A new rodent model of preeclampsia: Pregnant daughters from hypertensive placental ischemic moms have hypertension

Purpose: Studies show that daughters from hypertensive pregnancies are twice as likely to have preeclampsia (PE), pregnancy-induced hypertension (HTN) in comparison to women born from a normal pregnancy. PE affects ~5-10% of all births in the USA and is the leading cause of intrauterine growth restriction (IUGR). PE is associated with oxidative stress (OS) and cerebral damage. The causes of PE are unknown but is influenced by genetic and environmental conditions. Studies show that pregnancies involving placental insufficiency and HTN create an adverse environment that can affect the IUGR baby’s developmental programming and pregnancy outcomes.

This study aims to characterize the pregnancy of IUGR rat offspring from hypertensive placental ischemic moms. We hypothesize female rats born from pregnant hypertensive placental ischemic moms will have elevated blood pressure (BP) and OS.

Methods: Pregnant Sprague Dawley moms are divided into 2 groups: normal pregnant (NP) and the reduced uterine perfusion pressure (RUPP) hypertensive placental ischemic rats. On day 14 of pregnancy, the RUPP surgery is performed to generate PE. All dams (NP and RUPP) give birth naturally and weaned for 3 weeks. Offspring were then separated by sex and mother’s pregnancy status. ~10 weeks later, offspring were mated according to 4 groups: ♀NP x ♂NP (CON Preg, n=3), ♀NP x ♂RUPP (n=2), ♀RUPP x ♂NP (IUGR Preg, n=5), ♀RUPP x ♂RUPP (n=4). On day 19 of offspring pregnancy, BP was measured via carotid catheterization and the blood and brains were collected for analyses.

Results: IUGR Preg rats have elevated BP (116 ± 4.17 vs 100.6 ± 2.54 mmHg, p<0.02) and 8-isoprostanes (439.2 ± 13.61 vs 381.3 ± 26.10 g, ns), decreased circulating antioxidant capacity (AC) (0.33 ± 0.01 vs. 0.37 ± 0.01 mM Trolox/mg protein, p<0.01), and reduced body weight (330.1 ± 5.24 vs 350.3 ± 10.82 g, ns) compared to CON Preg rats. IUGR Preg rats have larger brains, suggesting brain swelling (5.38 ± 0.10 vs 4.95 ± 0.19 g/1000g BW, p<0.04). HSP-1 (186.1 ± 28.14 vs 100.0 ± 6.36 %HSP-1/protein/CON, p<0.04) and H2O2 (25.76 ± 2.95 vs 15.81 ± 4.56 μM/mg protein, ns), markers of ROS, are increased in the brains of IUGR Preg vs. CON Preg rats. Cerebral AC was slightly reduced (260.0 ± 33.14 vs 292.3 ± 13.91 uM Trolox/mg protein) and MnSOD (antioxidant) amounts were decreased (87.96 ± 3.43 vs 100.0 ± 2.84 %MnSOD/protein/CON, p<0.63).

Conclusion: IUGR Preg rats have increased systemic and cerebral OS, as well as larger brain sizes which may lead to cerebral damage. In summary, pregnant daughters from hypertensive placental ischemic moms show symptoms of a preeclamptic-like phenotype, thus creating a new model of PE. Future studies will determine the role of maternal PE status and OS in the development of HTN in pregnant IUGR offspring.