Periconceptional alcohol consumption-induced changes in embryonic prostaglandin E levels in mouse organogenesis: Modulation by nitric oxide

Abstract

The mechanisms of the teratogenic effects of maternal alcohol consumption remain unclear. The aim of the present work was to study the organogenic PGE 2 levels and the modulation of PGE 2 levels by NO after periconceptional alcohol ingestion. Female mice were intoxicated with a 10% ethanol in drinking water before pregnancy and up to day 10 of gestation. The PGE 2 released from organogenic embryos was measured by radio immunoassay following incubation with or without the addition of either a NO donor or a NO synthase (NOS) inhibitor. In the ethanol-treated females, we found increased percentages of retarded embryos, associated with a significantly elevated resorption rate ( p < 0.05 ), very high quantities of morphologically abnormal E.10 embryos ( p < 0.001 ) and significantly increased PGE 2 release, as compared to the embryo parameters of control females. While in the control-derived E.10 embryos the NO donor produced significantly increased PGE 2 release, in the ethanol-derived embryos decreased quantities of PGE 2 were observed. L-NMMA inhibited PGE 2 release in both control and ethanol-derived embryos at different concentrations, whereas it decreased PGE 2 content in controls but not in ethanol-derived embryos. The periconceptional alcohol ingestion produced excessive PGE 2 release, decreased PGE 2 content and disruption of the regulatory NO–PGE 2 pathways. These PGs alterations may be related to delayed organogenesis and abnormal neural tube development after chronic periconceptional consumption of alcohol.