Fetal Sex Does Not Influence Rates of Gastrulation-Stage Alcohol-Induced Craniofacial Malformations in C57BL/6J Mice

Prenatal alcohol exposure during mouse gastrulation (embryonic day [E] 7 in mice, corresponding to ~3rd week of human pregnancy) impairs eye, facial, and cortical development, recapitulating birth defects characteristic of Fetal Alcohol Syndrome (FAS). However, the impact of sex on the prevalence or severity of craniofacial features associated with FAS is currently unknown. The current study administered either alcohol (2.9g/kg, two i.p. doses, four hours apart) or vehicle control to pregnant C57BL/6J females on E7 and assessed fetal morphology at E17. Whereas sex did not affect fetal size in vehicle-treated litters, alcohol-exposed females were smaller than both control females and alcohol-treated males. Alcohol exposure increased the incidence of eye defects to a similar degree in males and females. Together, this suggests that females might be more sensitive to the general developmental effects of alcohol, but not to the effects of alcohol specifically on the craniofacies. We also established a developmental transcriptional baseline via whole transcriptomic analysis of untreated E7 embryos, and found 214 differentially expressed genes in females vs. males, including those in pathways related to cilia and mitochondria structure and function, histone demethylase activity, and pluripotency.