Harmful and beneficial effects of inflammatory response on reproduction: sterile and pathogen-associated inflammation

Abstract

In reproduction, inflammatory processes play important roles in the development of many pregnancy complications such as preterm labor/birth, recurrent pregnancy loss, recurrent implantation failure, and preeclampsia. Inflammation can be initiated by both microbial and non-microbial causes. Bacterial infection in the feto-maternal interface and uterus can provoke preterm labor/birth, miscarriage, and chronic endometritis. By contrast, inflammation without infection, or 'sterile inflammation,' can also lead to many kinds of complications, such as preterm labor/birth, miscarriage, or preeclampsia. Aberrant inflammation is facilitated by immune cells such as macrophages, dendritic cells, natural killer cells, and invariant natural killer T cells. In addition, cytokines, chemokines, and several kinds of inflammatory mediators are involved. On the other hand, appropriate inflammation is required for a successful offspring during the progression of the entire pregnancy. Herein, we discuss the relation between pregnancy and inflammation with immunological alterations. Understanding the role of inflammation in complications during pregnancy may establish new perspectives of the progress of normal pregnancy as well as treatments during pregnancy complications.

Mast Cell Activation Syndrome in COVID-19 and Female Reproductive Function: Theoretical Background vs. Accumulating Clinical Evidence

“…The release of key mediators during the activation and degranulation of MCs, including COVID-19-related MC activation, may significantly affect the course of many physiological and pathological reproductive processes in the human body, primarily influencing the permeability of vessels and vascular tone and indirectly modulating electrolyte and water balance or contents of the extracellular matrix [ 12 , 13 ]. Interestingly, the majority of the key physiological processes in the female reproductive tract, including menstruation, follicle development, ovulation, implantation, pregnancy, labor, and postpartum remodeling, consist of a readily visible inflammatory background [ 14 ]. Research successively provides new data.…”

Role of Inflammaging on the Reproductive Function and Pregnancy

“…Many studies have investigated the association of recurrent pregnancy loss (RPL) with immune dysfunction and inflammatory imbalance. Chronic inflammatory response may play an important role in the pathogenesis of miscarriage and implantation failure [ 90 ]. Many studies have reported high level of pro-inflammatory cytokines and chemokines, such as IL-6 [ 91 ], IL-8 [ 92 ], IL-10 [ 93 ], IL-18 [ 94 ], and TNF-α [ 95 ], in blood and decidua of women with RPL.…”

“…Chronic inflammation triggers Th1 polarization of immune cells and downregulation of Th2 response weakening the maternal immune tolerance to embryo implantation and increasing the risk of miscarriage [ 96 ]. Impaired regulatory T cells (Treg) function, together with low prevalence of natural killer (NK) and dendritic cells (DC) have been widely observed in the decidua of women with RPL [ 90 , 97 ]. As a result of innate immune dysfunction, chronic senescent cells accumulate in the decidua leading to SASP response has deleterious effects on implantation [ 84 ].…”

Targeting the Toll-like receptor pathway as a therapeutic strategy for neonatal infection

“…Sterile inflammation is classified as inflammation in the absence of infection; immune cells and their signaling molecules are responsible for this inflammation and can impact the onset of preterm labor or birth. Important endogenous molecules such as alarmins (HMGB1, HSP) released by damaged cells and PRRs induce sterile inflammation and may play important roles in the development of innate immunity during early life (24). The nature of the immune stimulation and the timing, severity, and duration of TLR activation will determine the response to infection and the long-term outcomes.…”