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- Enzymes present in neutrophil extracellular traps may stimulate the fibrogenic PGF(2 alpha) pathway in the mare endometriumPublication . Rebordão, Maria Rosa; Amaral, Ana; Fernandes, Carina; Silva, E; Lukasik, Karolina; Szóstek-Mioduchowska, Anna; Bravo, Pedro; Galvão, António; Skarzynski, Dariusz J.; Ferreira-Dias, GraçaEndometrosis is a fibrotic disease in mare endometrium whose pathological mechanisms remain obscure. Prostaglandin (PG)F2α, despite modulating reproductive physiological processes, may also provoke local pathological collagen deposition (fibrogenesis). Neutrophil extracellular traps (NETs) released during inflammation have been linked to fibrogenesis in several tissues. We have previously shown that enzymes found in NETs increase in vitro collagen production in mare endometrium. In this study, activation of PGF2α-pathway in equine endometrial explants challenged in vitro by enzymes found in NETs is shown. Our results indicate that both endocrine microenvironment (estrous cycle phase) and healthy or pathological conditions of endometrial tissues play an important role in PGF2α-pathway activation. In the endometrium of the follicular phase, we have observed both high production of PGF2α and/or PGF2α receptor gene transcription under the action of enzymes found in NETs, both conditions associated with fibrogenesis in other tissues. Nevertheless, transcription of the PGF2α receptor gene does not appear to be hormone-dependent, albeit their levels seem to be dependent on endometrial category in the mid-luteal phase. This study suggests that enzymes existing in NETs may instigate changes on PGF2α mediators, which may become an additional mechanism of fibrogenesis in mare endometrium.