Fetal sex and preterm birth.

Rates of preterm birth vary between different populations and ethnic groups. Epidemiologic studies have suggested that the incidence of preterm birth is also higher in pregnancies carrying a male fetus; the male:female difference is greater in earlier preterm pregnancy. Placental or chorion trophoblast cells from pregnancies with a male fetus produced more pro-inflammatory TNFα in response to LPS stimulation and less anti-inflammatory IL-10 and granulocyte colony stimulating factor (G-CSF) than cells from pregnancies with a female fetus, more prostaglandin synthase (PTGS-2) and less prostaglandin dehydrogenase (PGDH). These results suggest that in the presence of a male fetus the trophoblast has the potential to generate a more pro-inflammatory environment. Maturation of the fetal hypothalamic-pituitary-adrenal axis and expression of placental genes, particularly 11β hydroxysteroid dehydrogenase-2 are also expressed in a sex dependent manner, consistent with the sex-biasing influences on gene networks. Sex differences in these activities may affect clinical outcomes of pre- and post-dates pregnancies and fetal/newborn wellbeing. These factors need consideration in studies of placental function and in the development of personalized strategies for the diagnosis of preterm labor and postnatal health.