The effects of oxygen concentration on in vitro output of prostaglandin E2 and interleukin-6 from human fetal membranes

Abstract

Labour at all gestational ages has clear biochemical parallels with an inflammatory response, typified by the increased output of prostaglandins (PGs) and cytokines within the pregnant uterus. The main sources are the fetal membranes, including the amnion, chorion and decidua, and it is well established that stimuli [bacteria, bacterial endotoxins, interleukin (IL)-1β, corticotrophin releasing hormone and platelet activating factor], as well as negative regulators (progesterone and IL-10), control the net output of PGs and cytokines in vitro. In this study, we have investigated the effect of oxygen tension on fetal membrane biology, as a reconsideration of the literature suggests that fetal membranes are normally exposed to ∼3% O2 (∼20 mmHg) in vivo, rather than the 20% O2 (150 mmHg) used for in vitro culture. The output of prostaglandin E2 from non-activated fetal membranes in response to IL-1β was decreased by ∼80% at 16 and 24 h of culture, whereas the inhibition of IL-6 production was time-dependent, reaching 90% after 16 h and 50% after 24 h. Tissues obtained after labour (or after the activation of inflammatory processes leading to labour) were not inhibited by the low levels of oxygen, indicating that only before the onset of labour does oxygen regulate fetal membrane biology. The data identify oxygen as a regulator of fetal membrane inflammatory functions during human pregnancy, and its mechanism of action requires further study. © 2007 Oxford University Press.