Ethanol‐Induced Oxidative Stress and Mitochondrial Dysfunction in Rat Placenta: Relevance to Pregnancy Loss

Abstract

Background-Ethanol consumption during pregnancy increases the risk of early pregnancy loss and causes intrauterine growth restriction. We previously showed that chronic gestational exposure to ethanol impairs placentation, and that this effect is associated with inhibition of insulin and insulin growth factor signaling. Since ethanol also causes oxidative stress and DNA damage, we extended our investigations to assess the role of these pathological processes on placentation and placental gene expression.

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“…In developing rat placenta, TGCs are the main source of Prl3b1 [31], whose production starts in mid-gestation, and represent the dominant lactogenic hormone throughout the second half of gestation [12]. Herein, we found that gestational ethanol exposure significantly reduced placental Prl3b1 expression, particularly when the ethanol exposures were initiated on E15, consistent with previous observations [3]. While this effect could have been caused by altered differentiation in early exposure groups, ethanol-induced oxidative stress and apoptosis [3] also may have contributed to this outcome.…”

“…Herein, we found that gestational ethanol exposure significantly reduced placental Prl3b1 expression, particularly when the ethanol exposures were initiated on E15, consistent with previous observations [3]. While this effect could have been caused by altered differentiation in early exposure groups, ethanol-induced oxidative stress and apoptosis [3] also may have contributed to this outcome.…”

“…We used qRT-PCR to measure mRNA expression of trophoblast subtype-associated genes (Table 1) as previously described [3,25]. In brief, placental tissue was homogenized in Qiazol reagent using a TissueLyser II apparatus (Qiagen Inc., Valencia, CA).…”

“…Experimentally, gestational ethanol exposure mediates its adverse effects on fetal growth by: 1) impairing placentation, which is crucial for establishing the maternal-fetal interface needed for nutrient delivery and waste removal; 2) inducing oxidative stress, lipid peroxidation and DNA damage [3]. Previous studies focused on the adverse effects of ethanol on insulin/IGF signaling in relation to trophoblast cell motility and invasiveness, and linked these abnormalities to impairments in placentation, intrauterine growth restriction, and early pregnancy loss [4].…”

“…AAH is aninsulin/IGF-responsive gene, whose hydroxylase activity regulates cell motility and invasion [6,7]. Furthermore, gestational exposure to ethanol reduced the number of secondary trophoblast giant cells [4] and altered trophoblast subtype-specific gene expression [3].…”