The synergistic effects of prostaglandin and IL-1β on myometrial and cervical stromal cells at the onset of labor

Labor is a complex physiological process. As pregnancy reaches its culmination, the myometrium undergoes a transformation into a highly contractile and excitable state, becoming the driving force behind labor. Labor is carried out orderly by a series of preparations, of which the transition of myometrium cells from resting state to contraction state and the maturation and dilation of cervical cells are paramount [1,2]. Our previous study shows that the expression of 1626 genes and 135 proteins in myometrium changed after the initiation of labor [3]. The substantial transcriptional changes enriched biological processes involved in inflammation, gene expression, cell growth, cell communication, ion transport, muscle contraction, and other functions [3]. Parturition is an inflammatory event, without the presence of intrauterine infection, proinflammatory cytokines, chemokines, prostaglandins, and their receptors increase in expression near to parturition. Inflammatory events plays an important role in initiate of labor [[4], [5], [6], [7], [8]]. Macrophages and neutrophils infiltrate the maternal-fetal interface, enhancing the inflammatory microenvironment by releasing pro-inflammatory factors such as IL-1β and TNF-α, finally accelerating the labor onset [9,10]. IL-1β is regarded as an exceptionally early inflammatory mediator, pivotal for the initiation of labor, though its downstream regulatory mechanisms remain to be clarified.

Besides, prostaglandins (PGs) are also significant in regulating uterine contractions and maintaining cervical maturation [[11], [12], [13]]. PGs are divided into many subtypes, including PGE and PGF, both of which mainly acts on the cervix and myometrium, respectively. When the cervix expands progressively, the PGs level of amniotic fluid continues to increase, and the metabolites of PGs in maternal serum are also increased accordingly [14]. PGs have been clinically applied to induce labor in pregnancy, and PGs inhibitors are used to treat premature labor [15]. COX-2 is a rate-limiting enzyme for the synthesis of PGs. The COX-2 level is very low in the physiological state, but can be drastically stimulated during labor onset, such as IL-1β and oxytocin (OXT), thus promoting the secretion of PGs [16,17]. Therefore, PG is considered as one of the key factors during labor onset. However, the regulation mechanism is still not fully understood.

Although both IL-1β and PGs play an important role in the initiation of labor onset, the synergistic regulatory relationship between both is not yet clear. The purpose of this study is to investigate the changes of inflammatory factors in the myometrium during labor (the cervical tissue was not obtained due to ethical factors). Then, by using myometrium and cervical stromal cells to show how PGs are involved in the synergistic regulation of downstream proteins with IL-1β. So as to provide some theoretical basis for exploring the cause of labor.

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