Changes in nitric oxide levels in organogenic embryo and neural tube dysmorphogenesis alter murine periconceptional alcohol ingestion.

COLL T.; HOFMANN ORSETTI C.; GOLDSTEIN J.; PAZ D.A.; CEBRAL, E.

Los Cocos. Córdoba

Congreso; III Latin American Symposium on maternal-fetal interaction and placenta: basic & clinical research.; 2007

Maternal-fetal interaction society

Since the pathogenic mechanisms of organogenic CNS following maternal alcohol consumption are little known, the aim was to study the role of nitric oxide (NO) production in organogenic embryo and neural tube (NT) development after periconceptional alcohol ingestion. Female mice were intoxicated with 10% ethanol in drinking water for 15 days before and during pregnancy up to day 10 (T). Control females received water (C). T had increased % of organogenic embryos with open NT (5.4% vs 23.5%, p<0.001) and defective NT closure (4% vs 12%, p<0.001), disorganized neuroepithelium (H-E), reduced mitosis (p<0.01) and diminished body-cephalic proportion (scanning microscopy). A reduced T-derived embryo percentage with cephalic NT-neuronal nitric oxide synthase (nNOS) positive immunoreactivity (C: 80% vs T: 62.5%) was found. Endogenous and in-vitro T-embryo Nitrite (Ns) levels (Griess reaction, kit) were significantly diminished vs C-embryos (p<0.001, p<0.05). However, evaluation of the endogenous embryonic NOS activity by NADPH-diaphorase reaction showed a high % increase in whole embryos and cephalic region from the T-derived group. The increment of Ns levels (Griess), after either NO-donors (Nonoate) or NOS inhibitors (L-NMMA) incubations, suggested an increased positive response of NOS activity (Ns) in T-embryos. In conclusion, periconceptional alcohol ingestion induces deficient NO levels and/or dysregulated NOS expression/activity leading to abnormal neurogenesis, neurodegeneration of cephalic NT and probably embryofetal microcephaly.