Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy.

Raj Raghupathy,Julia Szekeres-Bartho

doi:10.3390/ijms23031333

Raj Raghupathy, Julia Szekeres-Bartho

Open Access

https://doi.org/10.3390/ijms23031333

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Abstract

Progesterone is well known for its numerous endocrinologic roles in pregnancy but is also endowed with fascinating immunomodulatory capabilities. It can downregulate the induction of inflammatory reactions, the activation of immune cells and the production of cytokines, which are critical mediators of immune responses. These features appear to be critical to the success of pregnancy, given the ability of maternal immune reactivity to interfere with pregnancy and to contribute to several pregnancy complications. This review summarizes the contribution of maternal immune effectors in general, and cytokines in particular, to pregnancy complications such as recurrent miscarriage, pre-eclampsia and preterm labor; it describes the promise offered by supplementation with progesterone and the oral progestogen dydrogesterone, as well as the progesterone-induced blocking factor in the prevention and/or treatment of these serious complications.

Highlights

Progesterone plays an impressive range of extremely important endocrinologic roles such as stimulating the growth of blood vessels that supply the endometrium, stimulating the endometrium to secrete nutrients that nurture the early embryo, preparing the uterine lining for implantation of the embryo and sustaining the endometrium throughout pregnancy
The crucial role of progesterone in immune crosstalk in the placenta was highlighted in a recent study, which showed that Brucella abortus infection in pregnant mice resulted in the suppression of progesterone production by the placenta, but that the administration of progesterone resulted in reduced production of inflammatory cytokines by trophoblast cells and reduced placental inflammation and increased viability of embryos [30]
We subsequently demonstrated that mitogen-stimulated peripheral lymphocytes from women with unexplained recurrent spontaneous miscarriage (RSM) produce significantly elevated levels of the pro-inflammatory cytokines IL-2, IFN-γ and tumor necrosis factor (TNF)-α, while on the contrary, women with a history of healthy pregnancy produce significantly greater levels of the anti-inflammatory Th2 cytokines IL-4, IL-5 and IL-10 [47,48]

Summary

Introduction

Progesterone plays an impressive range of extremely important endocrinologic roles such as stimulating the growth of blood vessels that supply the endometrium, stimulating the endometrium to secrete nutrients that nurture the early embryo, preparing the uterine lining for implantation of the embryo and sustaining the endometrium throughout pregnancy. The crucial role of progesterone in immune crosstalk in the placenta was highlighted in a recent study, which showed that Brucella abortus infection in pregnant mice resulted in the suppression of progesterone production by the placenta, but that the administration of progesterone resulted in reduced production of inflammatory cytokines by trophoblast cells and reduced placental inflammation and increased viability of embryos [30]. These observations clearly highlight the important immunoregulatory roles played by progesterone at the level of the placenta

Cytokines and Pregnancy Complications

Recurrent Spontaneous Miscarriage

Pre-Eclampsia

Findings

Preterm Delivery