Association between dietary soy prevention of fetal alcohol spectrum disorder and normalization of placental insulin and insulin-like growth factor signaling networks and downstream effector molecule expression.

Chronic prenatal alcohol exposure causes fetal alcohol spectrum disorder (FASD), often associated with impaired placentation and intrauterine growth restriction. Ethanol's inhibition of insulin and insulin-like growth factor Type 1 (IGF-1) signaling compromises trophoblastic cell motility and maternal vascular transformation at the implantation site. Previous studies have demonstrated that dietary soy effectively normalizes placentation and fetal growth in an experimental model of FASD. The studies were extended to better understand the mechanisms underlying soy's beneficial effects. Pregnant Long Evans rats were pair-fed with isocaloric liquid diets containing either 0% or 36% caloric ethanol from gestation day (GD) 6. The protein source in the diets consisted of either casein (standard and control) or soy isolate. On GD19, placentas were harvested to measure mRNA levels corresponding to major components of the insulin/IGF-1 pathway, as well as aspartyl-asparaginyl-β-hydroxylase (ASPH), Notch, and HES, which play critical roles in placentation. Chronic gestational ethanol exposure in rats fed diets containing casein significantly reduced the expression of insulin, insulin receptor,