The Placenta's Role in Sexually Dimorphic Fetal Growth Strategies

Fetal sex affects the risk of pregnancy complications and the long-term effects of prenatal environment on health. Some have hypothesized that growth strategies differ between the sexes, whereby males prioritize growth whereas females are more responsive to their environment. This review evaluates the role of the placenta in such strategies, focusing on (1) mechanisms underlying sexual dimorphism in gene expression, (2) the nature and extent of sexual dimorphism in placental gene expression, (3) sexually dimorphic responses to nutrient supply, and (4) sexual dimorphism in morphology and histopathology. The sex chromosomes contribute to sex differences in placental gene expression, and fetal hormones may play a role later in development. Sexually dimorphic placental gene expression may contribute to differences in the prevalence of complications such as preeclampsia, although this link is not clear. Placental responses to nutrient supply frequently show sexual dimorphism, but there is no consistent pattern where one sex is more responsive. There are sex differences in the prevalence of placental histopathologies, and placental changes in pregnancy complications, but also many similarities. Overall, no clear patterns support the hypothesis that females are more responsive to the maternal environment, or that males prioritize growth. While male fetuses are at greater risk of a variety of complications, total prenatal mortality is higher in females, such that males exposed to early insults may be more likely to survive and be observed in studies of adverse outcomes. Going forward, robust statistical approaches to test for sex-dependent effects must be more widely adopted to reduce the incidence of spurious results.