As a healthy placenta is essential for fetal growth, placental abnormalities can cause pathologies such as fetal growth restriction (FGR). Placenta growth is known to be affected by stressors, such as alcohol, during later stages of gestation; however, few studies have focussed on maternal exposure to stressors around the time of conception. Now, Karen Moritz and colleagues investigate the effects of periconceptional alcohol exposure (PC-EtOH) on the early stages of rat trophoblast formation and placentation. The authors show a number of sex-specific responses to early alcohol exposure; female embryos in particular have defects in trophoblast giant cell differentiation, which is later associated with reduced placental invasion and vascularisation. Although the underlying mechanisms are yet to be fully determined, the researchers describe links to alcohol-responsive epigenetic changes. For example, X-chromosome inactivation is perturbed and DNA methylation is increased in PC-EtOH embryos. Furthermore, they show that maternal choline, part of the one-carbon metabolism pathway that facilitates methylation, is reduced by PC-EtOH, which might explain the aberrant expression of imprinted genes. Taken together, this study describes sex-specific effects in the early embryo and placental growth in response to alcohol exposure, and provides new insight for the study of FGR.