Effects of gestational age on prostaglandin production and its regulation in human myometrial cells

The objective of this study was to evaluate the effects of known stimulants of prostaglandin production on cultured myometrial cells from women who are at various gestational ages. To evaluate this, myometrial segments were obtained from 12 patients at 27-40 weeks gestation at cesarean delivery. Myometrial cells were then isolated and grown to confluence in culture. Incubations were conducted in quadruplicate for 16 hours with interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA), or ionomycin. Prostaglandins E2, F2 alpha, and 6-keto F1 alpha (the stable metabolite of prostacyclin) were measured by radioimmunoassay and cellular protein determined. The results revealed that cultured myometrial cells produced prostaglandins in response to IL-1 beta, TNF-alpha, EGF, PMA, and ionomycin at all gestational ages tested at a significantly increased rate (P < 0.05 vs controls at and above 10 ng/ml of IL-1 beta, TNF alpha, and EGF; 1 microM for PMA, and 5 microM for ionomycin). The major prostaglandin produced in response to each stimulant was 6-keto-PGF1 alpha. Cultured human myometrial cells respond to known stimulants of prostaglandin production throughout the third trimester of pregnancy in the absence of labor. The myometrium may therefore be a source of prostaglandins that influences uterine activity.