Dose effect of gestational ethanol exposure on placentation and fetal growth

• Published in: Placenta (Eastbourne) Vol. 36; no. 5; pp. 523 - 530
• Main Authors: Gundogan, F, Gilligan, J, Qi, W, Chen, E, Naram, R, de la Monte, S.M
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-05-2015
• Subjects: Animals; Aspartyl-asparaginyl β-hydroxylase; Cell Adhesion - drug effects; Cell Line; Cell Movement - drug effects; Central Nervous System Depressants - administration & dosage; Central Nervous System Depressants - adverse effects; Embryo Implantation - drug effects; Ethanol - administration & dosage; Ethanol - adverse effects; Female; Fetal alcohol spectrum disorders; Fetal Development - drug effects; Fetal growth; Humans; Internal Medicine; Maternal Exposure - adverse effects; Mixed Function Oxygenases - metabolism; Obstetrics and Gynecology; Placental morphology; Placentation; Placentation - drug effects; Pregnancy; Rats, Long-Evans; Receptor, Notch1 - metabolism; Trophoblast; Trophoblasts - drug effects; Trophoblasts - metabolism; Fetal growth; Placental morphology; Fetal alcohol spectrum disorders; ASPH; Placentation; Aspartyl-asparaginyl β-hydroxylase; Trophoblast; gestation day; GD
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2015.02.010

Abstract Introduction Prenatal ethanol exposure compromises fetal growth by impairing placentation. Invasive trophoblastic cells, which mediate placentation, express the insulin-IGF regulated gene, aspartyl-asparaginyl β-hydroxylase (ASPH), which has a critical role in cell motility and invasion. The aims of this study were to characterize effects of ethanol on trophoblastic cell motility, and assess ethanol dose-dependent impairments in placentation and fetal development. Methods Pregnant Long Evans dams were fed with isocaloric liquid diets containing 0%, 8%, 18% or 37% ethanol (caloric content) from gestation day (GD) 6 to GD18. Fetal development, placental morphology, density of invasive trophoblasts at the mesometrial triangle, as well as placental and mesometrial ASPH and Notch-1 protein expression were evaluated. Directional motility of control and ethanol-exposed HTR-8/SVneo cells was assessed by ATP Luminescence-Based assay. Results Severity of fetal growth impairment correlated with increasing doses of ethanol. Ethanol exposure produced dose-dependent alterations in branching morphogenesis at the labyrinthine zone, and inhibited physiological transformation of maternal arteries. ASPH and Notch-1 protein expression levels were reduced, corresponding with impairments in placentation. Discussion Prenatal ethanol exposure compromises fetal growth and placentation in a dose-responsive manner. Ethanol's adverse effects on placental development are mediated by: 1) altered branching morphogenesis in labyrinthine zone; 2) suppression of invasive trophoblastic precursor cells; and 3) inhibition of trophoblastic cell adhesion and motility, corresponding with reduced ASPH and Notch-1 protein expression.