Alcohol consumption before pregnancy causes detrimental fetal development and maternal metabolic disorders

Alcohol consumption before or during pregnancy poses serious health risks to the fetus; however, the underlying mechanisms involved remain obscure. Here, we investigated whether ethanol consumption before pregnancy affects maternal or fetal health and whether pharmacological inhibition of CYP2E1, a...

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Bibliographic Details
Published in:Scientific reports 2020-06, Vol.10 (1), p.10054, Article 10054
Main Authors: Lee, Yoo Jeong, Kim, Ji Yeon, Lee, Dae Yeon, Park, Keon Jae, Kim, Gyu Hee, Kim, Jeong Eun, Roh, Gu Seob, Lim, Joong Yeon, Koo, Seul, Lim, Nam Kyoo, Park, Hyun Young, Kim, Won-Ho
Format: Article
Language:English
Subjects:
Alcohol Drinking - adverse effects
Alcohol use
Animals
Animals, Newborn
Cytochrome P-450 CYP2E1 Inhibitors - administration & dosage
Cytochrome P-450 CYP2E1 Inhibitors - pharmacology
Disease Models, Animal
Energy balance
Ethanol
Fatty liver
Fatty Liver - chemically induced
Female
Fetal Development - drug effects
Fetal Macrosomia - chemically induced
Fetal Macrosomia - drug therapy
Fetuses
Glucose - metabolism
Growth rate
Homeostasis
Homeostasis - drug effects
Inflammation
Insulin
Lactation
Macrophages
Metabolic disorders
Mice
Mitochondria
Neonates
Oxidation
Pregnancy
Pregnancy Complications - drug therapy
Prenatal Exposure Delayed Effects - drug therapy
Steatosis
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Summary:Alcohol consumption before or during pregnancy poses serious health risks to the fetus; however, the underlying mechanisms involved remain obscure. Here, we investigated whether ethanol consumption before pregnancy affects maternal or fetal health and whether pharmacological inhibition of CYP2E1, a major ethanol oxidation enzyme, by 4-methylpyrazole (4-MP) has therapeutic effects. We found that ethanol consumption (5%) 2 weeks before pregnancy resulted in a decrease in the number of viable fetuses and abnormal fetal development, and these effects were accompanied by impaired maternal glucose homeostasis and hepatic steatosis during pregnancy. Neonates of ethanol-fed mice had postnatal macrosomia and significantly decreased growth rates during the lactation period. However, treatment with 4-MP, a CYP2E1 inhibitor, markedly ameliorated the reduction in insulin action and glucose disposal responsiveness in the livers of ethanol-fed mice. Blockage of CYP2E1 significantly reduced the alteration in hepatic lipid deposition, fatty acid oxidation, mitochondrial energy status, and macrophage infiltration observed in ethanol-fed mice. Finally, there was a positive correlation between postnatal macrosomia or growth retardation and increased inflammatory responses. Collectively, our study suggests that even moderate ethanol intake may be detrimental to fetal development and may cause growth retardation through maternal metabolic disorders.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-66971-1