Many women of reproductive age consume alcohol, often at binge levels. Coupled with high rates of unplanned pregnancy (~50%), exposure of the early embryo to prenatal alcohol is inevitable in many pregnancies. Additionally, ~40% of Australian women continue to consume alcohol throughout pregnancy, albeit at lower levels. Impacts on the development, morphology and function of the placenta likely underlie the increased risk of pregnancy complications and long-term adverse outcomes associated with prenatal alcohol exposure. Typically, adaptations by the placenta to pregnancy complications are sex-specific.
Our recent systematic review and meta-analysis, across 33 included clinical studies, has shown that prenatal alcohol exposure increases the likelihood of placental abruption and is associated with decreased placental weight; and altered placental vasculature, DNA methylation and molecular pathways. However, only a single study examined placentas by fetal sex, confirming sex-specific outcomes.
We have utilised our unique rat model of periconceptional ethanol exposure, from 4 days prior to mating until embryonic-day 4 (E4), to further explore potential sex-specific changes in the placenta. The periconceptional period is a critical time when exposure to an adverse environment can impact the pregnancy and program long-term disease in offspring. This model results in female-specific alterations in trophoblast outgrowth capacity in the early embryo at E5, as well as reduced maternal blood space volume in the placenta at E15. There is also evidence of global hypermethylation in the blastocyst, indicative of inappropriate epigenetic reprogramming, along with reduced maternal plasma choline levels and altered components of the one-carbon metabolism pathway in the E20 placenta. Placental efficiency was reduced and there was increased accumulation of glycogen in late gestation female placentas. Our results highlight that alcohol should not be consumed by women during pregnancy or when planning a pregnancy, and that public health campaigns should target prevention prior to conception.