Oral Presentation ESA-SRB Conference 2015

Periconceptional alcohol exposure - uterine and blastocyst contributions to offspring health (#152)

Karen Moritz 1
  1. University of Queensland, St Lucia, Qld, Australia

Perturbations around the time of conception have long lasting effects on adult health of the offspring. ~ 80% of Australian women drink alcohol around the time of conception but cease upon pregnancy recognition. We have developed a model of periconceptional alcohol exposure (PCE) in which rats are exposed to alcohol for the 4 days prior to conception until day 4 of gestation. PCE resulted in fetal growth restriction and offspring with severe adult insulin resistance, increased fat deposition, as well as renal and cardiac dysfunction. We have examined the placenta in late gestation and found striking sex-specific alterations in placental morphology suggesting impaired placental development may contribute to disease outcomes. The placenta is composed of both maternal and blastocyst derived tissues and optimal placental formation is dependent upon orchestrated interactions between embryonic trophoblast cells and endometrial cells of a receptive uterus.  Our recent studies have focussed on the effects of alcohol on the maternal uterine environment and the blastocyst. At E5, following PCE, we have demonstrated altered expression of markers of receptivity including elevated expression of uterine sensitization-associated gene-1 (Usag-1) suggesting the uteri of the dams exposed to PCE become receptive earlier than control dams and may not optimally synchronize with arrival of the blastocyst in the uterus.  Studies on the blastocyst have determined that PCE does not affect cell number. However, using trophoblast stem (TS) cell cultures, we found alcohol could directly affects the ability of trophoblast cells to proliferate, differentiate and interact with the maternal endometrium as evidenced by decreased expression of several trophoblast subtype-specific markers. Finally, we have determined that PCE results in widespread changes in genes that regulate epigenetic status including the DNA methyltransferases (DNMTs) in fetal organs in later gestation. Together these studies suggest that alcohol around conception has multiple effects on early developmental processes including uterine receptivity, placental development and methylation patterns which combine, contribute to the growth restriction and long term disease outcomes.