Effects of perigestational alcohol ingestion in the organogenesis and early placentation, in mouse. Role of vasoactive factors

ELISA CEBRAL Y DANTE PAZ

Los Cocos, Córdoba, Argentina

Workshop; International Workshop “Latest concepts in Developmental Biology”.; 2006

Little is known about the teratogenic actions of perigestational alcohol consumption on the organogenesis and early placentation, in mouse. The objectives of our work were to study the alcohol effects on the embryo-placental development and the role of vasoactive factors [nitric oxide (NO), prostaglandins (PGs)] in the modulation of these processes. Female mice were treated with 10% alcohol in drinking water for 15 dasy previous to fecundation and during gestation up to day 10 (organogenesis and early placentation). Controls received water (C). In the alcohol-treated females (A), we found increased resorption rate with retarded differentiation and growth, reduced embryo vitality and elevated number of morphologically abnormal embryo (scanning), where the principal embryonic anomaly was the defective neural tube development. The increased PGE synthesis (RIA), the alterations of the NO levels (Griess reaction) and disrupted NO-PGE pathway (in-vitro experiments), suggested that these altered cellular factors and the increased oxidative stress would trigger the organogenic defects. On the other hand, since the placentopathies, that originate recurrent miscarriages, preeclampsia, fetal growth retardation, prematurity, congenic malformations, are commonly associated with maternal alcohol consumption, we studied the effects of perigestational 10% alcohol exposition on the early placentation. Moreover, PGs and NO participate in the angiogenesis, the decidualization, the control of miometrial relaxation. Therefore we investigated the role of these vasoactive factors and their relationships in the early placental formation, in the implantation site (IS) of day 10 of pregnancy. High % of IS from A had low decidualized Decidua Basalis and Capsularis, low development of villous, collapsed intervillous space in the labyrinth zone and uncompleted closure of uterine lumen (HyE). The immunostaining of the endothelial nitric oxide synthase (eNOS) (immunohistochemistry) and the inducible NOS (iNOS) (immunofluorescence, confocal), increased in IS from A in the placental and trophoblastic zone. The endogenous PGF2 and nitrates/nitrites levels resulted significantly increased in miometrial (M) and decidual (De) tissues from A-IS. Both M and De-PGF2 release were significatively reduced with COX-1 and 2 inhibitors, in C and A-IS. However, the M and De-PGF2 levels from A-IS, did not diminish after incubation with a NOS inhibitor. The addition of a NO-donor increased the M and De-PGF2 levels of C-IS, but only De-PGF2alfa levels was modified. We concluded that vasoactive factors would be involved in the regulation of some organogenic functions and in the embryo-maternal interaction. Their biochemical-cellular alterations, toghether with increased oxidative stress, would conduce to deregulation of the maintenance of normal gestation and overcome abnormal placentation, playing an important role in the embryo-fetal pathogenesis associated with maternal alcohol consumption.