The Role of Chemokines in Term and Premature Rupture of the Fetal Membranes: A Review1

Abstract

Several studies indicate that at the choriodecidual interface, where maternal and fetal tissues make contact, a network of signals is established during labor that includes infiltration of leukocytes and secretion of pro-inflammatory cytokines. In this review, we provide an overview of the inflammatory milieu present in the choriodecidua during membrane rupture, describe the recruitment and homing of leukocytes to the reproductive tissues, and detail specific actions of the key chemokines released by the choriodecidual cells. These data lend further support to the hypothesis that labor is an inflammatory response, wherein the infiltrated leukocytes in the choriodecidua interface could be contributing to the creation of a microenvironment leading to collagenolysis, which would promote the rupture of these tissues during labor. In addition to the available information describing biological actions of chemokines during various pathological conditions such as infection, preterm labor and preterm rupture of membranes suggest that these compounds play important roles in other gestational events such as cervical dilation and myometrial contractions. Even though we do not know the totality of biochemical signals that integrate the molecular dialogue between leukocytes and the various gestational tissues, it is becoming increasingly evident that this microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the fetal membranes. Therefore, chemokines should be considered as important regulatory molecules with the ability to initiate the events that characterize normal and pathological labor.

Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators

“…IL-8 is a potent chemotactic, mediating neutrophil chemotaxis and activation. Inducible by IL-1␤ and TNF-␣ (Mittal et al, 2010), it is thought that the main role of IL-8 is to maintain the incursion of neutrophils and perpetuate the inflammatory response (Gomez-Lopez et al, 2010). The findings of our current study demonstrate that IL-1␤ decreases Slit2 mRNA in myometrium and that Slit2 silencing is also associated with an increase in IL-8 mRNA expression and release, suggesting that Slit2 might play a regulatory role during inflammatory chemotaxis.…”

Pregnancy disorders appear to modify the risk for retinopathy of prematurity associated with neonatal hyperoxemia and bacteremia

“…In early sets of analyses, we adjusted for gestational age in two ways, by both week of gestation (23, 24, 25, 26, 27), and by groups of weeks (23–24, 25–26, 27). Similar qualitative results were obtained and we present the data adjusted for gestational age in groups of weeks.…”

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

“…For example, pro-inflammatory cytokines induce the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) in the chorioamniotic membranes and decidua, leading to the increase in local and amniotic fluid concentrations of prostaglandins [36-40] that contribute to the transition from myometrial quiescence to labor initiation [41]. These data suggest that cytokines and chemokines orchestrate the activation of decidual tissue during labor [20]. …”