Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System

• Published in: Biology (Basel, Switzerland) Vol. 11; no. 9; p. 1264
• Main Authors: Martín-Estal, Irene, Fajardo-Ramírez, Óscar R., Bermúdez de León, Mario, Zertuche-Mery, Carolina, Benavides-Guajardo, Rodolfo, García-Cruz, María Isabel, Rodríguez De Ita, Julieta, Castilla-Cortázar, Inma, Castorena-Torres, Fabiola
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 25.08.2022; MDPI
• Subjects: antioxidant enzyme system; Antioxidants; Apoptosis; CYP2E1; CYP2E1 gene; Cytochrome; Cytochrome P450; Dehydrogenases; Enzymes; Ethanol; Females; Fetuses; Gene expression; Genotypes; Hormones; IGF-1 deficiency; Insulin; Insulin-like growth factor I; Insulin-like growth factors; Kinases; Laboratory animals; Liver; Males; Metabolism; Metabolites; Mutation; Placenta; Polymerase chain reaction; Pregnancy; Proteins; Reactive oxygen species; Risk factors; Rodents; Side effects; Signal transduction; Teratogenicity; Vagina; United States > US; Mexico
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology11091264

Ethanol use during pregnancy is a risk factor for developing adverse outcomes. Its metabolism by cytochrome P450 2E1 (CYP2E1) produces radical oxygen species (ROS), promoting cellular injury and apoptosis. To date, no studies have been conducted to elucidate the teratogenic effects due to both IGF-1 deficiency and ethanol consumption in mice placentas. The aim of this study is to determine the effect of ethanol consumption on the placenta and liver of partially IGF-1-deficient mice, the role of metabolism via CYP2E1, and the antioxidant enzyme system. Heterozygous (HZ, Igf1+/−) pregnant female mice were given water or 10% ethanol. Wild-type (WT, Igf1+/+) female mice were used as controls. At gestational day 19, pregnant dams were euthanized, and maternal liver and placentas were collected. Pregnant HZ dams were smaller than controls, and this effect was higher due to ethanol consumption. Cyp2e1 gene was overexpressed in the liver of HZ pregnant dams exposed to ethanol; at the protein level, CYP2E1 is reduced in placentas from all genotypes. The antioxidant enzymatic system was altered by ethanol consumption in both the maternal liver and placenta. The results in this work hint that IGF-1 is involved in intrauterine development because its deficiency exacerbates ethanol’s effects on both metabolism and the placenta.