Defective placentation in perigestational alcohol ingestion, in mouse. Role of prostaglandins and nitric oxide pathways

CEBRAL, E; FALETTI, AB; CLADOUCHOS, ML; PAZ, DA

Santiago, Chile

Simposio; II Simposio Latinoamericano Interacción materno-Fetal y Placenta; 2005

SLIMP

II Simposio Latinoamericano Interacción Materno-Fetal and Placenta Desde la Investigación Básica a la Clínica     DEFECTIVE PLACENTATION IN PERIGESTATIONAL ALCOHOL INGESTION, IN MOUSE. ROLE OF PROSTAGLANDINS AND NITRIC OXIDE PATHWAYS.   a E.Cebral, b A. Faletti, a M.L. Cladouchos, a D.A Paz. a Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Departamento de Biodiversidad y Biología Experimental (DBBE), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab.II, Ciudad Universitaria (PO. 1428EHA), b Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Buenos Aires, Argentina.   Alterations in prostaglandins (PGs) and nitric oxide (NO) levels would be involved in abnormal placentation. The aims were to evaluate the early placentation after maternal alcohol ingestion and the role of PGs and NO in this process. Methods: female mice were treated with 10% alcohol 15 days previous to superovulation and during gestation up to day 10 of pregnancy (A). Controls (C) received water. At day 10, the endothelial and inducible nitric oxide synthases (eNOS, iNOS) were immunolocalized in the implantation site (IS). In miometrial (M) and decidual (De) tissues the PGE, PGF2alfa and nitrates/nitrites (Ns) content were determined by RIA and the Griess reaction respectively. M and De were incubated with or without Indomethacin, Meloxicam, L/D-NAME (NOS inhibitor), s-Nonoate (NO donor) and PGF2alfa released assessed by RIA. Results: the A-IS had low decidualized Decidua Basalis and Capsularis, low development of villous with collapsed intervillous space in labyrinth and altered trophoblastic zone. The villous and trophoblastic eNOS and iNOS expression increased in A-IS. The PGF2 and Ns content significantly increased in A-M and De. Both M and De-PGF2 release were significantly reduced with Indo and Melox in C and A. L-NAME diminished the PGF2 in A-M and S-Nonoate inhibited the A-De-PGF2 levels. Conclusions: the perigestational alcohol intake produced early resorption and defective placentation due to low decidualization, abnormal villous and trophoblastic zona and high NO-oxidative stress. The increased PGF2 and altered NO-PGF pathway would lead to deregulation of the maintenance of uterine relaxation and overcome abnormal angiogenesis and placental circulation. Supported by CONICET Grant Resol.Nr.1008 and PIP CONICET 2309(Argentina).