Impairment of the antifibrotic prostaglandin Epathway may influence neutrophil extracellular traps-induced fibrosis in the mare endometrium.

Abstract

Prostaglandin E(PGE) has contradictory effects in many organs. It may have proinflammatory, anti-inflammatory, or anti-fibrotic roles, depending on the type of receptors to which it binds. By signaling through its receptors EP2 and EP4, PGEmediates anti-inflammatory and anti-fibrotic actions. In spite of chronic endometrial fibrosis (endometrosis) being a major cause of mare infertility, its pathogenesis is not fully understood. We have shown that contact of mare endometrium in vitro with neutrophil extracellular traps (NETs) proteases favors endometrial collagen type I production. Therefore, we investigated the involvement of the PGEpathway in collagen deposition in mare endometrium, challenged in vitro with proteases present in NETs. Mare endometria (Kenney and Doig categories I/IIA and IIB/III), obtained in the follicular phase (FLP) and mid-luteal phase (MLP), were incubated for 24 h with components found in NETs (elastase, cathepsin-G, and myeloperoxidase). Secretion of PGEand transcripts for specific PGE synthase (PGES) and PGEreceptors (EP2 and EP4) were evaluated. Impaired PGEproduction and low EP2 transcript abundance depended on the endometrial category and estrous cycle phase. Impairment of PGEand/or EP2 might play a role in FLP (category IIB/III) and MLP (I/IIA) endometrial fibrogenesis because of the reduction in its antifibrotic capacity. In conclusion, priming of the endometrium with endogenous ovarian steroids might inhibit the antifibrotic PGEpathway either in healthy or pathologic tissues with collagen formation after NETs proteases action.