Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF_2α Pathway in the Mare Endometrium

• Main Authors: Maria Rosa Rebordão, Ana Amaral, Carina Fernandes, Elisabete Silva, Karolina Lukasik, Anna Szóstek-Mioduchowska, Pedro Pinto-Bravo, António Galvão, Dariusz J. Skarzynski, Graça Ferreira-Dias
• Format: Article
• Language: English
• Published: MDPI AG 2021-09-01
• Series: Animals
• Subjects: neutrophil extracellular traps; fibrosis; endometrium; endometrosis; horse; PGF_2α
• Online Access: https://www.mdpi.com/2076-2615/11/9/2615

Endometrosis, a fibrotic disease of mare endometrium, impairs uterine function. Prostaglandins (PG), despite modulating reproductive physiological functions, may also cause local pathological collagen deposition (fibrogenesis). We have previously shown that neutrophil extracellular traps (NETs) may also favor mare endometrosis. The aim of this study was to investigate the effect of enzymes present in NETs on PGF_2α-pathway activation. Kenney and Doig’s type I/IIA and IIB/III mare endometria, from follicular phase (FLP) and mid-luteal (MLP) phase, were cultured in vitro in the presence of NETs enzymes (elastase, cathepsin-G or myeloperoxidase). Production of PGF_2α (EIA) and transcription (qPCR) of its synthases (<i>PTGS2</i>, <i>AKR1C3</i>) and receptor (<i>PTGFR</i>) genes were evaluated. PGF_2α and <i>PTGFR</i> were influenced by endometrial category and estrous cycle phase. In FLP endometrium, NETs enzymes induced both high PGF_2α production and/or <i>PTGFR</i> transcription. In MLP type I/IIA tissues, down-regulation of <i>PTGFR</i> transcripts occurred. However, in MLP type IIB/III endometrium, high levels of <i>PTGFR</i> transcripts were induced by NETs enzymes. As PGF2α-pathway activation facilitates fibrogenesis in other tissues, PGF2α may be involved in endometrosis pathogenesis. In the mare, the endocrine microenvironment of healthy and pathological endometrium might modulate the PGF_2α pathway, as well as fibrosis outcome on endometrium challenged by NETs enzymes.