Oxidative stress and cellular and tissue damage in organogenic outbred mouse embryos after moderate perigestational alcohol intake.

COLL T; CHAUFAN G; PEREZ TITO L G; VENTUREIRA M R; SOBARZO C M A; RIOS DE MOLINA M.C.; CEBRAL E

MOLECULAR REPRODUCTION AND DEVELOPMENT

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: New York; Año: 2017 vol. 84 p. 15 - 24

1040-452X

Perigestational alcohol consumption up to organogenesis in CF-1 mouse led to retarded early embryo development and neural tube defects. Here, we addressed whether perigestational alcohol ingestion up to day 10 of gestation induces oxidative stress and changes in macromolecules and organ tissues of early organogenic embryos. Adult CF-1 female mice were administered 10 % ethanol in drinking water for 17 days previous to mating and up to day 10 of gestation (TF). Control females were administered ethanol-free water (CF). Our results demonstrated significantly reduced catalase activity and expression level (western blot) and increased glutathione content in the embryos from TF. The nitrite level was significantly reduced, but TBARS content (thiobarbituric acid reactive substances), an index of lipid peroxidation, did not change. In TF-derived embryos compared to controls, immunoexpression of 3-nitrotyrosine (3-NT) detected in all tissues correlates with high levels of 3-NT proteins (western blot). The apoptosis (TUNEL-positive cells/embryo tissue area) significantly increased in ectoderm and mesoderm but not in heart, which did express (immunohistochemistry) higher cleaved caspase-3-positive cells/area of ventricular myocardium than in controls. This study demonstrated that perigestational moderate alcohol ingestion up to day 10 of gestation induces oxidative stress by altering radical nitrogen species and antioxidant enzymatic and non-enzymatic mechanisms. In consequence, generalized protein nitration related to debalanced nitric oxide levels associated with tissue-specific apoptosis were detected in embryos exposed, suggesting that oxidative mechanisms may play an important role in perigestational alcohol-induced malformations of exposed organogenic embryos.