Myometrial prostaglandin E₂ synthetic enzyme mRNA expression: Spatial and temporal variations with pregnancy and labour

We have investigated the hypothesis that the expression of the enzymes involved in PGE₂ synthesis in the human uterus is co-ordinated. We have studied (i) the mRNA expression of the enzymes involved in PGE₂ synthesis [phospholipases (cPLA₂ and sPLA₂), prostaglandin H synthase (PGHS)-2 and PG E synthases (PGES-1 and -2)] and their relationship to the expression of inflammatory cytokines in samples of myometrium obtained from pregnant women undergoing caesarean section (LSCS) either before or after the onset of labour at or before term; and (ii) the effect of IL-1β, IL-6, TNF-α, PGE₂ and stretch on PGE₂ enzyme mRNA expression. We found that cPLA₂, sPLA₂ and PGHS-2 mRNA expression were greater in labour samples; cPLA₂, sPLA₂, PGHS-2, PGES-1 and -2 mRNA expression were greater in lower - than upper-segment samples; and there was no effect of gestational age. PGHS-2 mRNA levels correlated with those of PGES-1, cPLA₂, IL-1β and IL-8; PGES-1 mRNA levels correlated with those of IL-1β, IL-8 and cPLA₂. In primary cultures of uterine myocytes, cPLA₂ mRNA expression was increased by IL-1β and IL-6; PGHS-2 mRNA expression was increased by IL-1β, PGE₂ and stretch; and PGES-1 mRNA expression was increased by IL-1β only. These data show that labour is associated with increased expression of the enzymes involved in PGE₂ synthesis and their expression is greater in the lower uterine segment. The presence of associations between the levels of PGE₂ enzyme mRNA expression and the effects of IL-1β suggest that their expression is co-ordinated and that IL-1β is the responsible factor.