70: Altered fetal brain programming in a preeclampsia-like mouse model and its prevention by prenatal treatment with pravastatin

Hypertension/Physiology

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tic pathways by which maternal administered Magnesium Sulfate attenuates fetal inflammation. In this study we have demonstrated IL-1␤ attenuation may be an important pathway by which Magnesium Sulfate exerts its anti-inflammatory effects in the maternal but not in the fetal compartment. Further studies are needed to better elucidate this pathway. Research supported by the Oxenhorn family.

IL-1␤ levels within the maternal and fetal compartments Maternal Blood

Fetal Blood

Amniotic Fluid

Fetal Brain

Placenta

SSS

31.2 +/6.8

126.8 +/29.6

100.4 +/12.6

0.014 +/0.002

0.090 +/0.017

SLS

419.6 +/60.1

262 +/20.7

159.7 +/16.6

0.051 +/0.014

0.146 +/0.030

MLM

208.9 +/30.1

241.7 +/72.9

158.5 +/15.1

0.031 +/0.0158

0.168 +/0.110

The data are represented as means ⫹/⫺ SEM. The concentrations within the maternal blood, fetal blood and amniotic fluid are in pg/ml and the placenta and fetal brains are in pg/␮g of protein. Groups are SSS, saline-saline-saline; SLS, saline-LPS-saline; MLM, MgSO4-LPS-MgSO4.

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3-months of age. RNA was extracted from the frontal cortex (FrC), hypothalamus (HT), and cerebellum. Quantitative RT-PCR was used to measure mRNA expression along pathways involved in apoptosis (Glial fibrillary acidic protein, GFAP), neuronal migration (Reelin), hypoxia (Hypoxia-induced factor 1-alpha), oxidative stress (Cyclooxygenase 2; Inducible nitric oxide synthase), and myelin and its related inflammation (Myelin basic protein (MBP); Amyloid precursor protein). One or two-way ANOVA were used as appropriate for statistical analysis. RESULTS: GFAP and reelin expression were up-regulated 2- and 4-fold in the FrC of sFlt offspring compared with control (p⫽0.025 and 0.006 respectively). MBP expression was up-regulated 4-fold in sFlt offspring HT (p⬍0.001). Prenatal pravastatin therapy restored expression to levels similar to control (Figure). No gender effect was seen. Expression was similar between groups for all other genes and in the cerebellum. CONCLUSION: Preeclampsia alters developmental programming of pathways for apoptosis, neuronal migration, and myelin inflammation in the frontal cortex and hypothalamus. Maternal therapy with pravastatin restores the normal development of these pathways.

*Indicates P value ⬍ 0.05 SLS vs SSS whereas; **Indicates P value ⬍ 0.05 SLS vs MLM.

70 Altered fetal brain programming in a preeclampsia-like mouse model and its prevention by prenatal treatment with pravastatin

mRNA expression at 3 months of age

Alissa Carver1, Maged Costantine1, Esther Tamayo1, Huaizhi Yin1, J Regino Perez-Polo2, George Saade1 1 University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX, 2University of Texas Medical Branch, Biochemistry & Molecular Biology, Galveston, TX

OBJECTIVE: Preeclampsia alters fetal programming and results in long-term outcomes in the offspring. Pravastatin, a hydrophilic drug that does not cross the placenta, prevents preeclampsia in animal models. This study aims to describe the role of preeclampsia and pravastatin therapy on fetal brain programming using a mouse model. STUDY DESIGN: At gestation day 8, pregnant CD-1 mice were randomized to tail vein injection with adenovirus carrying soluble Fms-like tyrosine kinase 1 (sFlt-1) or murine immunoglobulin G2Fc (mFc; control). sFlt-1 dams received pravastatin (5mg/kg/d; sFlt-pra group) or water (sFlt group) until weaning, and mFc received only water (mFc group). Offspring (n⫽10-11/group) were sacrificed at

Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology

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