Sex Difference of Fetal-Originated Disease

Adverse conditions during pregnancy can lead to the development of fetal multi-organ function in a sex-specific manner, mediated by the maternal-placenta-fetal biological unit. This can result in sex differences in both birth outcomes and susceptibility to adult diseases. The susceptibility to fetal-originated disease caused by adverse prenatal environments is closely related not only to the sex-specific development of the fetal hypothalamic-pituitary-adrenal axis and its regulatory center, the hippocampus but also to the way in which the placenta regulates fetal development. This chapter focuses on the sex differences in fetal-originated disease, specifically fetal-originated metabolic and psychoneurotic diseases. It provides a comprehensive summary of the sex differences in the developmental programming of the hypothalamic-pituitary-adrenal axis and hippocampus as well as the placental adaptive changes in offspring under prenatal adverse environments. This chapter is important for understanding the sex differences in fetal birth outcomes and the long-term consequences thereof. It lays the groundwork for exploring personalized diagnosis and early prevention and treatment strategies for fetal-originated disease.