Introduction Prematurity remains a leading cause of neonatal morbidity and mortality. A better understanding of what triggers spontaneous preterm labour (PTL) may allow the development of novel therapies to arrest the process. Labour is associated with inflammatory processes, but little is known about the nature or timing of these events. We hypothesized that macrophage infiltration of uterine tissues is an early event in the labour process.
Method Rat models were used to examine the timing of inflammatory events. Multiple sections of pregnant uteri on day (d) 21, 22 (am and pm), 23 (term labour) and d1 and 4 postpartum were collected. Uteri were also collected from two models of PTL induced by mifepristone (d16 and 19). Macrophages were identified in fixed uterine sections by immunohistochemistry and quantified by image analysis.
Results Macrophage numbers were significantly increased in both decidua and myometrium during labour (p<0.05). Importantly decidual macrophage infiltration occurred 12 h prior to labour (d22pm vs d21; p<0.05), while myometrial infiltration occurred during labour (d23 vs d22pm; p<0.05). Macrophages were more abundant (5-fold higher) in the decidua than myometrium. Elevated macrophage numbers were detected in the decidua in both PTL models (p<0.05), with a similar trend in myometrium.
Conclusions These studies confirm that decidual inflammatory events precede labour, and occur prior to myometrial macrophage infiltration, supporting a role for the decidua in triggering labour. Intervening in the labour process at an early stage, for example blocking decidual inflammation, may allow the development of a more successful treatment to prevent PTL.
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