77 Role of Placental PAPP-A and IGF-II in placental growth in hypoxia-induced fetal growth restriction

Abstract

Fetal growth restriction (FGR) is associated with an increased risk of perinatal and neonatal mortality. Insulin-like growth factors (IGFs) play a major role in fetal growth through PAPP-A-IGF signaling. IGF-II, specifically, is involved in development of placental exchange into late gestation. Chronic hypoxia can result in FGR through mechanisms of placental dysfunction. We hypothesize that chronic hypoxia-exposure decreases placental PAPPA- and IGF-II protein expression resulting in FGR. Female guinea pigs (GPs) were time-mated with male GPs. Pregnant sows (term gestation = 65 days) were randomly assigned to either normoxia (NMX, room air, 21% O2) or hypoxia (HPX, 10.5% O2) during the last 14 days of pregnancy. At near-term gestation, anesthetized female fetuses were removed via hysterotomy. Fetal body, organ (brain, liver, heart) and placenta weights (wt) were recorded. Asymmetric FGR was classified as fetal wt 0.66. Placental tissues of 7 NMX and 7 HPX-FGR male GPs were homogenized and protein expression of PAPP-A and IGF-II was measured by Western blot. NMX and HPX were compared using Student’s t-Tests with statistical significance determined at p value < 0.05. In the NMX and HPX-FGR cohorts, there was no statistical difference in the mean gestational age at delivery 63.7d and 62.4d (p=0.07), respectively. As expected, fetal body wt, brain, and liver wt were significantly less in the HPX-FGR cohort as compared to NMX (Table 1). Relative placenta wt was increased by 25% with HPX (p<0.05). There was no statistical difference in PAPP-A expression in NMX and HPX placentas (1.22 ± .28 vs 1.55± .79, p=0.353, respectively). IGF-II expression was significantly increased in HPX-FGR placentas (0.58 ± .13 vs 1.22 ±.34, p=0.05), (Figure 1). Contrary to our hypothesis, neither PAPP-A nor IGF-II were decreased with hypoxia. Rather, hypoxia increased IGF-II, which is consistent with an increase in relative placental wt. This suggests a unique role for IGF-II as mechanism of compensatory placental growth response, despite the presence of FGR.View Large Image Figure ViewerDownload Hi-res image Download (PPT)