Periconceptional alcohol consumption-induced changes in embryonic prostaglandin E levels in mouse organogenesis: modulation by nitric oxide.
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.
Cebral
Elisa
E
Laboratorio de Biología del Desarrollo, Instituto de Fisiología, Biología Molecular y Neurociencias, DBBE, Facultad de Ciencias Exactas y Naturales-UBA, Ciudad Universitaria, CBA, Buenos Aires, Argentina. ecebral@hotmail.com
Faletti
Alicia
A
Jawerbaum
Alicia
A
Paz
Dante
D
D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D038081:Organogenesis / Q000187:drug effects; D011247:Pregnancy; D011458:Prostaglandins E / Q000378:metabolism*; D011863:Radioimmunoassay; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D011458:Prostaglandins E; D019323:omega-N-Methylarginine; D000431:Ethanol; D019001:Nitric Oxide Synthase