Review: Understanding the role of androgens and placental AR variants: Insight into steroid-dependent fetal-placental growth and development.

The role of steroids throughout pregnancy and their effect on placental physiology is well established, especially for estrogens, progestogens, and glucocorticoids; however, the role of androgens - particularly within the context of placental physiology - remains largely unexplored. Androgens are often defined as the male sex-steroids and are fundamental for the defeminisation and masculinisation of male fetuses. Therefore, the placenta may adapt to these steroids in a sex-specific manner, with males being more receptive to changes in these steroids concentrations, when compared with females; however, their involvement in female intrauterine development has been investigated in several studies and may suggest females have a level of responsiveness to these steroids. While the former may be true, studies have reported sex-specific differences in the expression and activity of factors involved in androgen biosynthesis and bioavailability, with males consistently demonstrating greater degrees of altered protein and gene expression when compared with females. Understanding the placental androgen axis is essential as many pregnancy comorbidities are associated with elevated concentrations of androgens and perturbed intrauterine development or growth. Indeed, it appears that specific pathophysiologies of pregnancy can modulate the activity of key factors involved in the placental androgen axis and this may contribute to the etiology of sex-specific developmental outcomes from certain pregnancy complications. This review will provide insight into what is currently known regarding androgen signalling and the human placenta, and how this complex system may regulate sex-specific growth and developmental outcomes in normal and adverse pregnancies.