In vivo and in vitro models for implantation studies in maternal alcohol ingestion. Role of matrix metalloproteinases and cell adhesion molecules

CEBRAL, E

Puerto Varas

Simposio; SLIMP-Maternal-Fetal Interaction; 2017

SLIMP

During the implantation, complex events of trophoblast invasion and penetration take place into maternal uterus to conduct normal embryonic development at post-implantation stages. In preimplantation, cavitation, expansion and hatching of the blastocyst as well as the correct expression and assembly of cell adhesion molecules, are requirements for the beginning of the implantation. During the implantation window, the trophoblast differentiation and invasiveness becomes relevant to lead the complete penetration of the embryo into the maternal tissue (day 8 of gestation).Throughout implantation, the matrix metalloproteases (MMPs), the key regulatory mediators in the placental cells, are involved in regulating trophoblast invasion to maintain a normal utero-placental homeostasis and to determine the proper embryo development and fetal survival at term. Dysregulation of these mechanisms may lead to early embryo loss. In vitro implantation as well as the ectoplacental cone explants and culture are useful to study the implantation loss, the inadequate trophoblast invasiveness and the maternal-fetal interaction defects, addressing the quantity and quality of adaptive and/or altered processes at periimplantation stages. Complications of pregnancy and embryo loss due to perigestational alcohol consumption up to early pregnancy were reported previously by us. Alcohol 10 % exposure before gestation and up to day 4 of gestation induced disassembly and altered expression of E-cadherin and ZO-1 leading to abnormal cavitation and expansion of the blastocysts. At day 5 of gestation, the reduced number of hatched-implantative embryos resulted in delayed embryo development at advanced implantation stages (24 and 48 h of in vitro culture). During in vitro implantation, the trophoblast invasiveness was dysregulated, which can lead to deficient expansion of the ectoplacental cone (EC) in vivo (day 8 of gestation). In parallel with the reduced expansion of EC at 24 and 48 h of in vitro EC-culture, the in vivo studies revealed diminished EC-MMP-9 gene and protein expression. Instead, the increase of MMP-2 expression in the proliferative zone of the EC was detected with diminish E-cadherin in trophoblast cells and maternal-fetal interface. Perigestational alcohol consumption produces imbalances of MMP-2 and -9 expressions in trophoblast cells during peri-implantation stages probably conducting to the embryo resortion seen at early organogenesis (day 10 of gestation) and/or abnormal placenta at term.