It is well established that a poor in utero environment may contribute to increased risk of developing adult disease. The period around the conception is now recognised as a window of particular susceptibility as women are often unaware they are pregnant and continue to engage in risky behaviours. WHO and NHMRC guidelines state “Not drinking is the safest option for pregnant women and women planning a pregnancy” but almost 50% of pregnancies in Australia are unplanned and up to 70% of women are drinking in the time leading up to conception. Our research program has developed a rodent model of periconceptional alcohol exposure and utilised this to explore the phenotypic outcomes and the underlying mechanisms involved.
Alcohol around conception resulted in fetal growth restriction and offspring with insulin resistance, increased fat deposition and impaired renal and cardiac function. Similar to other models of exposure to alcohol during periods of brain development, our model resulted in neuro-behavioural deficits including anxiety like behaviour and a depressive phenotype. Investigation of the early embryo suggested that the alcohol exposure caused sex-specific changes to the growth and differentiation of the pre-implantation embryo including changes to DNA methylation. This contributed to poor placental development and changes to the regulation of the hypothalamic-pituitary-adrenal axis including the isoforms of the glucocorticoid receptor. This work highlights that maternal alcohol consumption, even prior to blastocyst implantation and placental formation, can result in long lasting deficits in the offspring.