Progesterone: A Unique Hormone with Immunomodulatory Roles in Pregnancy

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.

Dysregulated low-density granulocyte contributes to early spontaneous abortion

“…This study discovered that the Nets formation during pregnancy increased in peripheral blood and decidua, and this is consistent with the view that human pregnancy is associated with a mild pro-inflammatory state characterized by circulatory neutrophil activation (47). Nets formation during pregnancy was regulated in a multi-mode manner, such as HCG and CSF could promote NETosis, while progesterone restrained the NETotic process (48,49). In the mouse model of early pregnancy, abundant Nets formation at the maternal-fetal interface could lead to fetal death (14).…”

Sex-biased adaptive immune regulation in cancer development and therapy

“…Progesterone (P4) is an endogenous steroid sex hormone with increased secretion by the ovaries during menstruation and pregnancy ( DeMayo et al., 2002 ). P4 is primarily known to regulate female reproductive functions by stimulating the growth of blood vessels that supply the endometrium, preparing the uterine lining for implantation, and sustaining the endometrium during pregnancy ( Raghupathy and Szekeres-Bartho, 2022 ). Whereas males and females have no substantial quantitative difference in progesterone levels at baseline, P4 does have an important role in several male biological processes, including spermiogenesis ( Oettel and Mukhopadhyay, 2004 ).…”

Progesterone, cerclage, pessary, or acetylsalicylic acid for prevention of preterm birth in singleton and multifetal pregnancies – A systematic review and meta-analyses

“…14 Two levels based on some study limitations, inconsistency (I 2 27%), indirectness and serious imprecision. 15 Two levels based on serious inconsistency (I 2 72%), and indirectness (high PTB rate). 16 Two levels based on serious imprecision and no definition of gestational diabetes mellitus in three trials.…”

“…Progesterone is an essential hormone to maintain a pregnancy until term. It modulates the immune response (15) and is also suggested to reduce the production of prostaglandins, thereby inhibiting myometrial contractions and cervical ripening (16)(17)(18). The available administration routes are vaginal, oral, or intramuscular (im) injection.…”