title: 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.
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom.
authors: Sylvia
authors: S
authors: Lui
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom ; Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Rebecca L
authors: RL
authors: Jones
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom ; Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Nathalie J
authors: NJ
authors: Robinson
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom ; Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Susan L
authors: SL
authors: Greenwood
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom ; Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: John D
authors: JD
authors: Aplin
authors: Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, St. Mary's Hospital, Manchester, United Kingdom ; Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors: Clare L
authors: CL
authors: Tower
mesh_terms: D000079:Acetaldehyde / Q000633:toxicity*; D000596:Amino Acids / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D010920:Placenta / Q000187:drug effects / Q000473:pathology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism*; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000596:Amino Acids; D000431:Ethanol; D000079:Acetaldehyde