Progesterone-Related Immune Modulation of Pregnancy and Labor

Abstract

Pregnancy involves a complex interplay between maternal neuroendocrine and immunological systems in order to establish and sustain a growing fetus. It is thought that the uterus at pregnancy transitions from quiescent to laboring state in response to interactions between maternal and fetal systems at least partly via altered neuroendocrine signaling. Progesterone (P4) is a vital hormone in maternal reproductive tissues and immune cells during pregnancy. As such, P4 is widely used in clinical interventions to improve the chance of embryo implantation, as well as reduce the risk of miscarriage and premature labor. Here we review research to date that focus on the pathways through which P4 mediates its actions on both the maternal reproductive and immune system. We will dissect the role of P4 as a modulator of inflammation, both systemic and intrinsic to the uterus, during human pregnancy and labor.

Steroids, Pregnancy and Fetal Development

“…Both, progesterone and glucocorticoids, are significantly involved in the regulation of immune responses (4,7,11). The structural similarities between glucocorticoids and progesterone raise the intriguing concept of mutual, interrelated as well as individual pathways elicited by these hormones.…”

“…The genomic effects of progesterone and glucocorticoids are mediated by the intracellular progesterone and glucocorticoid receptors (PR and GR), which belong to a subfamily of the nuclear receptor superfamily (4,7,12). Upon binding to ligands, PR and GR translocate to the cell nuclei, where they interact with specific regions of the DNA to act as transcription factors that modulate gene expression (7,11,12).…”

“…Besides the PR, progesterone can elicit non-genomic actions by binding to G-protein coupled membrane progestin receptors (membrane progesterone receptors: mPR) and the so-called progesterone receptor membrane components (PGRMC) [reviewed in (4)]. Among them, mPRalpha/PAQR7 and mPRbeta/PAQR8 as well as PGRCM1 and 2 are present in T cells (20,29) and mPRalpha is expressed in particular fractions of circulating Tregs (42).…”

“…Progesterone is essential for the establishment and continuation of pregnancy (3). Progesterone not only plays multiple immunomodulatory functions (4), but also it supports uterine receptivity and quiescence (3,5). Additionally to sex steroids, maternal glucocorticoids dramatically increase over the course of pregnancy in order to meet the increasing energy demands (6).…”

Towards an understanding of women's brain aging: the immunology of pregnancy and menopause

“…Hence, similar to the dose-dependent effects of E2 on the immune system [190], adequate and balanced levels of androgens may contribute to preventing negative health outcomes in women after menopause. Similarly to E2 and androgens, high levels of progesterone may also suppress the activity of RA and MS via the inhibition of Th1 pathways [206,207]. On a neural level, one study demonstrated that a single 100 mg progesterone implant, increasing levels to those of pregnancy, mitigated demyelination and microglia reaction in a focal demyelination mouse model [208].…”