Embryo-trophoblast development after perigestational alcohol exposure in the CD-1 mouse.

ELISA CEBRAL

Mar del Plata

Simposio; SLIMP and V LASRI. Maternal-Fetal Interaction: From Fertilization to the Next Generation.; 2015

SLIMP

Previously we established a mouse semi-chronic moderate alcohol intake paradigm, previous to- and up to mid gestation, for the study of prenatal origin and inducer factors of Fetal Alcohol Syndrome (FAS). In this model, perigestational alcohol exposure up to day 10 of gestation, increases the risk of embryo resorption, delays the development, leads to microcephaly and early defects of neural tube closure and produces placental vascularization defects in organogenesis, by altering different celular and molecular pathways. However, the susceptibility and induction pattern of embryo-trophoblast abnormalities at earlier stages of development, of exposed CD-1 females (TF), were not known. The aim was to investigate the effects and molecular mechanisms of perigestational alcohol intake up to peri-implantational stages, in CD-1 mouse. Maternal alcohol 10% administration up to day 4, 5 or 8 of gestation, led to delayed differentiation, increased abnormal embryos, decreased growth by deregulating the cell division, and induced high incidence of nuclear abnormalities and apoptosis. During implantation (in vitro culture) the embryos with reduced growth (?smaller embryos?) from TF, evidenced over-increased outgrowth at 72 h of culture, suggesting a stimulation of trophoblast invasiveness induced by alcohol exposure. However, on day 8 of gestation, the ectoplacental cone (in vivo studies), showed no proliferative zone and reduced expanded zone, consistent with the diminished viability of cultured cones (in vitro studies). Thus, in TF, the dynamics of trophoblast expansion, through implantation to gastrulation, varied and resulted deregulated, suggesting that the observed increased MMP-2 protein expression in the proliferative zone as well as the decreased MMP-9 gene and protein expression in the cone, may be altered mechanisms of growth and early trophoblast invasiveness. The perigestational alcohol CD-1 intake up to periimplantational stages induces early embryo-trophoblast defects that can lead to gestational loss, fetal anomalies and morphofunctional alterations of the placenta, at term.