Early embryo-maternal factors involved in fetus-placental anomalies induced by perigestational alcohol consumption

CEBRAL E

Iguazu Falls

Congreso; V SLIMP Latin American Symposium on Maternal-Fetal Interactions & Placenta and IV Latin American Symposium on Reproductive Immunology; 2013

SLIMP

Early embryo-maternal factors involved in fetus-placental anomalies induced by perigestational alcohol consumption  Elisa Cebral, PhD. Laboratory of Reproduction and Maternal-Embryonic Physiopatology. IFIBYNE-CONICET. Biodiversity and Experimental Biology Department. FCEN, University of Buenos Aires, Buenos Aires, Argentina  Moderate alcohol consumption prior to gestation and up to mid-gestation in mice is able to cause, at term, embryo reabsortions, fetal external and skeletal malformations, and placental weight reduction and vascularization disruption. The complex regulatory signals and their interactions in the early embryo and trophoblast-decidual cells are potential targets for direct and/or indirect alcohol adverse effects. Early delayed differentiation, defective embryo growth, abnormal morphogenesis, inadequate trophoblast invasiveness, altered embryo-placental vascularization may be related to disruption of metabolic, cellular, nuclear and molecular pathways at gastrulation and organogenesis times. At days 7-8 of gestation, retarded differentiation, abnormal embryo tissues and alterations in maternal-fetal interface appeared associated with defective metalloproteinases (MMPs) expression and apoptotic mechanisms. At day 10, perigestational ethanol consumption induced neural tube defects and up-regulation of embryonic cadherin expressions, disruption of the regulatory nitric oxide (NO)-prostaglandin (PG) pathways, altered MMPs, oxidative stress, lipoperoxidation and protein nitration. In trophoblast-decidual tissues, besides these similar alcohol-effects, growth factors (VEGF) and expression of extracellular matrix components were also affected. Moreover perigestational alcohol exposure is able to produce embryo differentiation retardation, abnormal blastocyst growth and impaired trophoblast invasion earlier at days 4-5, suggesting that preimplantation embryos, and perhaps oocytes, have significantly susceptibility and strongly negatively influenced by ethanol intake. The maternal alcohol induced-genotoxicity may also contribute to the abnormal embryo-placental development. We propose links between changes in early embryo-placental NO-PG pathways, MMP expression/activity, growth factors, oxidative status and maternal genotoxicity with fetal-placental developmental damage at term after alcohol deprivation from mid-gestation times in the mouse model.