Detrimental Effects of Ethanol and Its Metabolite Acetaldehyde, on First Trimester Human Placental Cell Turnover and Function

Abstract

Fetal alcohol spectrum disorder (FASD) describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol) and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6). The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, p<0.05, N = 8–9) (cell line: 5% at 20 mM and 40 mM, p<0.05, N = 6). Acetaldehyde also reduced Ki67-positive cells in both experiments (explants at 40 µM p<0.05; N = 6) (cell line at 10 µM and 40 µM; p<0.05; N = 7). Only in the cell line at 20 µM acetaldehyde demonstrated increased apoptosis (p<0.05; N = 6). Alcohol inhibited taurine transport in BeWo cells at 10 mM and 40 mM (p<0.05; N = 6), and in placenta at 40 mM (p<0.05; N = 7). Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6). Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6). Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of FASD by reducing placental growth. Alcohol also reduces the transport of taurine, which is vital for developmental neurogenesis.

Prenatal ethanol exposure and placental hCG and IGF2 expression

“…In accordance with previous studies, we have observed an increase in apoptosis markers after the ethanol exposure [9,36,39]. Our study has evidenced a strong correlation between ethanol dose and hormonal release in the supernatant culture medium Determination of hCG and IGF2 in placental tissue obtained from fetuses exposed or not to ethanol.…”

“…The consequences of prenatal ethanol exposure (PEE) observed in infants could be attributable, in part, to the damage exerted to the cells and, as consequence, this cell system losses partially its function [9]. For this reason, biomarkers that offer reliable information about the injury produced in the fetus are necessary [6,10].…”

Alcohol, Methamphetamine, and Marijuana Exposure Have Distinct Effects on the Human Placenta

“…Animal models of FASD have demonstrated detrimental effects of prenatal alcohol exposure on placental size, structure, and function, although the majority of studies have been conducted in vitro using cell cultures and/or tissue sections (Burd et al., ). Alcohol exposure has been associated with trophoblast cell death via apoptosis in human placenta‐derived cell cultures (Clave et al., ; Lui et al., ) and decreased placental size (Andersson et al., ; Hollstedt et al., ; Kaminski et al., ; Niemelä et al., ). In a rat model, Gundogan and colleagues () found an alcohol‐related decrease in placental thickness, with the greatest effects in the labyrinthine layer, as well as an increase in untransformed maternal vessels, which result in diminished placental blood flow and nutrient transfer to the fetus.…”

Latest Evidence on Alcohol and Pregnancy

“…Studies have shown that alcohol alters the growth and function of the placenta (Lui et al., ). Alcohol consumption increases the risk of preterm birth and infants born small for their gestational age (Nykjaer et al., ).…”