Abstract P210: Sex Specific Changes In Cerebral Proinflammatory Cytokines In Intrauterine Growth Restricted Offspring

Abstract

Background: Intrauterine growth restriction (IUGR) often times results from placental ischemia, which restricts the distribution of nutrients and oxygen to meet the metabolic demand of the growing fetus. IUGR offspring (OS) have an increased risk for developing cerebrovascular diseases (CVD) later in life. Factors for development of CVDs are HTN and inflammation. Our lab has shown 17 week IUGR male rats from preeclamptic pregnancies have HTN and elevated inflammation via systemic IL-17, while our females show no change. The role of inflammation to cause HTN in IUGR offspring in a sex specific manner is unknown and the major focus of this study which examines the changes in cerebral inflammation IUGR offspring at 12 weeks. We hypothesize that cerebral inflammation in IUGR males will be elevated, while no change in female IUGR offspring will be observed. Methods: IUGR offspring originate from preeclamptic Sprague Dawley dams. OS weaned for 3 weeks and were separated by sex and IUGR status. At 12 weeks, the rats underwent carotid catheterization to measure BP. Brains were collected to measure pro-inflammatory cytokines, such as TNF-α and IL-17 via ELISAs. Results: At 12 weeks, all OS were normotensive. Brain TNF-α increased in female IUGR (17,366± 1,500 vs 8,116± 1,341 pg/mL, p<0.05) and was elevated in male IUGR (20,845±7571 vs 8,516±1712 pg/mL, ns). Brain IL-17 increased in male IUGR (13,580± 945 vs 9,620± 945 pg/mL, p<0.05) and was elevated in female IUGR (13,143± 1613 vs 10,930± 696 pg/mL, ns). Systemic IL-17 was increased in IUGR male OS (112±16.8vs100±3.9 IU/Protein/CON %, ns). Conclusion: At 12 weeks, brain TNF-α and IL-17 were elevated in IUGR males and females. The differences in expression of each cytokine between the sexes suggest that IL-17 contributes to the increase in BP, especially in males. Understanding the timing of these developments could help to elucidate the role of inflammation in the development of CVD with or without HTN. This study is clinically relevant as it provides a sex specific inflammatory target for therapeutics, to help prevent hypertension and CVD in IUGR offspring. In the future, we will evaluate the role of inflammation in IUGR offspring in a sex specific manner.