Decidualization and maintenance of a functional prostaglandin system in human endometrial cell lines following transformation with SV40 large T antigen

Abstract

Prostaglandins (PGs) are key regulators of reproductive function and associated pathologies. We have established stable endometrial stromal and epithelial cell lines with SV40 large T antigen (TAG) as a model to study PG action in the human endometrium. Two clones for each cell type were selected for rapid growth, PG production and response to interleukin-1beta (IL-1beta). The resulting stromal (HIESC) and epithelial (HIEEC) cells retain their characteristics for at least 40 population doublings (PDs). The selected clones express progesterone (PR) and estrogen receptor-alpha (ER-alpha) at both mRNA and protein levels. By contrast, with the existing known human endometrial cell lines Ishikawa and KLE, HIESC and HIEEC increase their production of PGF2alpha and PGE2 and cyclooxygenase (COX)-2 protein expression in response to IL-1beta. The latter cells also express the main biosynthetic enzymes involved in PG production, cytosolic phospholipase A2 (PLA2), COX-1 and COX-2, PGF synthase and PGE synthase and the corresponding EP2, EP3, EP4 and FP receptors. The selective COX-2 inhibitor NS-398 completely inhibits the increased production of PGs induced by IL-1beta in both cell types, whereas dexamethasone (DEX) exerts a stronger inhibition in HIESC than in HIEEC. The latter observation may be related to the higher expression of COX-1 measured in HIEEC. On the basis of the present characterization and previous determination of corresponding primary cell cultures, HIESC and HIEEC appear appropriate to study the contribution of PGs in the regulation of human endometrium function and associated pathologies.