Impact of Estrogen and Progesterone on Immune Cells and Host–Pathogen Interactions in the Lower Female Reproductive Tract

Abstract

Microbial infections are a threat to women’s reproductive health. Although reproductive cycles and pregnancy are controlled by sex hormones, the impact of hormones on host–pathogen interactions and immune function in the female reproductive tract are understudied. Furthermore, the changing endocrine environment throughout pregnancy may influence how and when women are susceptible to ascending infection. Because most intrauterine microbial infections originate in the lower reproductive tract, it is vital that future studies determine how different hormonal conditions influence the lower reproductive tract’s susceptibility to infection to understand temporal components of infection susceptibilities across pregnancy. These studies should also extend to nonpregnant women, as it is critical to establish how hormonal fluctuations across the menstrual cycle and hormonal contraceptives may influence disease susceptibility. This review summarizes current knowledge of how estrogen and progesterone impact vaginal and cervical mucosal immunity, barrier function, and interactions with microbial communities.

Global perspectives on the burden of sexually transmitted diseases: A narrative review

“…By fostering social cohesion, building support networks, and promoting community-led approaches to health promotion and advocacy, stakeholders can empower communities to address the social determinants of health, challenge stigma and discrimination, and create environments that promote sexual health and well-being for all individuals. [ 60 ] This may involve supporting community-based organizations, providing training and capacity-building opportunities, and facilitating collaboration and knowledge sharing among diverse stakeholders.…”

Innate and Adaptive Immune Systems in Physiological and Pathological Pregnancy

“…These novel therapeutics and/or different perspectives of existing therapeutics will offer new options for the optimal health of the pregnant individual and fetus. Hormonal control of the maternal immune system also needs to be taken into account, as reviewed here [ 23 , 24 , 25 ], as some specific cell subtypes can be altered such as antigen presentation by ILCs [ 223 ].…”

“…Much remains to be learned about how the innate and adaptive immune systems work together throughout gestation in both physiological and pathological pregnancy. Furthermore, levels of hormones are known to change tremendously during pregnancy and their impact on the immune system have recently been reviewed extensively [ 23 , 24 , 25 ]. Therefore, this will not be a focus of the current review.…”

Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR

“…To address this critical lack of knowledge, we carried out a series of structural, biochemical, and cellular experiments to elucidate the binding and induction mechanisms of MtrR by female and male steroidal hormones as they are physiologically relevant molecules that would confront gonococci during infection. In the female reproductive tract, gonadol hormones are responsible for the coordination of immune cell function, vaginal microbiome, and epithelial cell architecture during menstration to optimize maternal protection against pathogen infection and also fetal implantation and survival 26 – 28 . This results in a “window of vulnerability” where the immune protection is dampened in the reproductive tract in order to optimize sperm and fetal survival, which can be taken advantage of by pathogens 26 , 27 .…”

“…In the female reproductive tract, gonadol hormones are responsible for the coordination of immune cell function, vaginal microbiome, and epithelial cell architecture during menstration to optimize maternal protection against pathogen infection and also fetal implantation and survival 26 – 28 . This results in a “window of vulnerability” where the immune protection is dampened in the reproductive tract in order to optimize sperm and fetal survival, which can be taken advantage of by pathogens 26 , 27 . Thus, pathogens can utilize hormones to regulate gene expression involved in cytotoxic stress defenses allowing host infection 26 , 29 – 34 .…”