A Potential Role and Contribution of Androgens in Placental Development and Pregnancy

Abstract

Successful pregnancy requires the establishment of a highly regulated maternal–fetal environment. This is achieved through the harmonious regulation of steroid hormones, which modulate both maternal and fetal physiology, and are critical for pregnancy maintenance. Defects in steroidogenesis and steroid signaling can lead to pregnancy disorders or even fetal loss. The placenta is a multifunctional, transitory organ which develops at the maternal–fetal interface, and supports fetal development through endocrine signaling, the transport of nutrients and gas exchange. The placenta has the ability to adapt to adverse environments, including hormonal variations, trying to support fetal development. However, if placental function is impaired, or its capacity to adapt is exceeded, fetal development will be compromised. The goal of this review is to explore the relevance of androgens and androgen signaling during pregnancy, specifically in placental development and function. Often considered a mere precursor to placental estrogen synthesis, the placenta in fact secretes androgens throughout pregnancy, and not only contains the androgen steroid nuclear receptor, but also non-genomic membrane receptors for androgens, suggesting a role of androgen signaling in placental function. Moreover, a number of pregnancy disorders, including pre-eclampsia, gestational diabetes, intrauterine growth restriction, and polycystic ovarian syndrome, are associated with abnormal androgen levels and androgen signaling. Understanding the role of androgens in the placenta will provide a greater understanding of the pathophysiology of pregnancy disorders associated with androgen elevation and its consequences.

The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses

“…All except one of these seven replicated metabolites were androgenic steroids and, therefore, were highly correlated. Steroids are important for numerous functions during gestation, particularly for normal placental function [ 40 ]. Here we present evidence of a potential causal effect (associated in metabolomic analyses with consistent direction of effect in the MR analyses) of positive associations between maternal gestational androgenic steroid metabolites and offspring CHDs.…”

Steroidomics of Pregnant Women at Advanced Age

“…On the other hand, we expanded to more types of hormones, especially the distribution of androgens. There were few studies focused on androgen levels in P and the differences in their synthesis and secretion ( 14 ). The results of our study are consistent with those in Yoshida’s report ( 15 ), which also used the MS.…”

“…Androgens are known to secrete at a woman’s ovaries, adrenal glands, and placenta, the main source during pregnancy. Recent studies reported that androgen levels of pregnant women increased in maternal plasma compared with those in non-pregnant women ( 19 ), as precursors for E2 synthesis, DHEA and T, play essential roles in pregnancy ( 14 ). It is particularly noteworthy that androgen levels increase further when women have pregnancy complications related to placental dysfunction.…”

The relationship of maternal gestational mass spectrometry-derived metabolites with offspring congenital heart disease: results from multivariable and Mendelian randomization analyses

“…All except 1 of these 7 replicated metabolites were androgenic steroids and so were highly correlated. Steroids are important for numerous functions during gestation, particularly for normal placental function 40 . Here we present evidence of a potential causal effect (associated in metabolomic analyses with consistent direction of effect in MR analyses) of positive associations between maternal gestational androgenic steroid metabolites and offspring CHDs.…”