Periconceptional influences on offspring sex ratio and placental responses.

Maternal diet and secondary factors can strikingly influence fetal outcomes, including biasing offspring sex ratio and altering the molecular biological responses of the conceptus, namely within the placenta. Alterations in the in utero environment might also lead to profound developmental origin of health and disease (DOHaD) outcomes into adulthood, including increased risk for cardiovascular disease, obesity and cancer, with males in general being at greater risk for these diseases. Female mice maintained on a very high fat (VHF) diet birth more sons than those on a chow-based and low fat (LF), high carbohydrate diet, with the latter group producing more daughters. However, neither the underlying mechanisms that contribute to this shift in offspring sex ratio nor when they occur during pregnancy have been resolved. In this review, we consider the evidence that maternal diet and other factors influence secondary sex ratio in a variety of species, including humans, and discuss when this skewing might occur. Additionally, we examine how fetal sex and maternal diet influences gene expression patterns in the mouse placenta, which serves as the primary nutrient acquisition and communication organ between the mother and her developing pups. These adaptations to diet observed as changes in gene expression are likely to provide insight into how the placenta buffers the fetus proper from environmental shifts in nutrient availability during pregnancy and whether male and female conceptuses respond differently to such challenges.