Prenatal ethanol exposure-induced a low level of foetal blood cholesterol and its mechanism of IGF1-related placental cholesterol transport dysfunction

Abstract

Clinical researches showed that intrauterine growth retardation (IUGR) foetus had decreased blood cholesterol levels. The present study aimed to confirm that prenatal ethanol exposure (PEE) caused decreased blood cholesterol levels in IUGR foetal rats and elucidate its placental mechanism. Pregnant Wistar rats were intragastrically administrated with ethanol (4 g/kg.d) on gestational days 9–20 (GD9–20). in vivo, PEE increased the levels of total cholesterol (TCH), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in maternal serum, whereas decreased them in both female and male foetal serum. Moreover, the expression of cholesterol transport genes, scavenger receptor class B type 1 (SCARB1), low-density lipoprotein receptor (LDLR), ATP binding cassette subfamily A member 1 (ABCA1) and ATP binding cassette subfamily G member 1 (ABCG1) was reduced in female and male placentas in the PEE group. Meanwhile, the proliferation decreased and the apoptosis increased in female and male placentas, and the insulin like growth factor 1 (IGF1) signal pathway was inhibited. in vitro, after being treated with ethanol (15, 30, 60, 120 mM) for 72 h, the expression of cholesterol transport genes was decreased, the apoptosis was increased, the proliferation was decreased and the IGF1 signal pathway was inhibited in BeWo cells, whereas exogenous IGF1 reversed these changes. In conclusion, by inhibiting the IGF1 signal pathway in placentas, PEE induced apoptosis and inhibited proliferation, thus decreased the cholesterol transport in placentas, and eventually leading to low blood cholesterol levels in foetal rats.