Rebordão Maria Rosa, Amaral Ana, Lukasik Karolina, Szóstek-Mioduchowska Anna, Pinto-Bravo Pedro, Galvão António, Skarzynski Dariusz J, Ferreira-Dias Graça
CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal; Coimbra College of Agriculture, Polytechnic Institute of Coimbra, Coimbra, Portugal.
CIISA - Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
Theriogenology. 2018 Jun;113:8-18. doi: 10.1016/j.theriogenology.2018.02.001. Epub 2018 Feb 7.
Neutrophil extracellular traps (NETs) are DNA complexes carrying nuclear and cytoplasmic proteins, such as elastase (ELA), cathepsin-G (CAT) and myeloperoxidase (MPO). Mare endometrosis is a chronic degenerative process characterized by excessive collagen in endometrium. While NETs fight bacteria that cause endometritis, they may trigger endometrial fibrogenesis. The aim was to evaluate the in vitro effect of some NETs components on mare endometrial fibrogenesis and determine its relationship with histopathology or estrous cycle. Endometrial explants were incubated with NETs components (ELA, CAT, MPO or oxytocin). Collagen type I (COL1) protein and type I and III (COL3) gene transcription were evaluated in follicular and mid-luteal phases endometria (Kenney and Doig type I/IIA and IIB/III). Increased COL1 occurred with all NETs proteins, although endometrial response to each NETs protease depended on estrous cycle and/or endometrial category. Since ELA enhanced COL1 production, NETs persistence might be linked to endometrosis. Estrous cycle influenced COL1 protein concentration and COL3 transcripts, suggesting that follicular phase may favor endometrial collagen production. However, luteal phase endometria with moderate or severe lesions may be also susceptible to fibrotic effects of NETs constituents. These data propose that NETs involvement in chronic endometritis in mares may act as putative endometrial fibrogenic mediators.
中性粒细胞胞外诱捕网（NETs）是携带核蛋白和胞质蛋白的DNA复合物，如弹性蛋白酶（ELA）、组织蛋白酶G（CAT）和髓过氧化物酶（MPO）。母马子宫内膜炎是一种慢性退行性病变，其特征是子宫内膜中胶原蛋白过多。虽然NETs可对抗引起子宫内膜炎的细菌，但它们可能引发子宫内膜纤维化。本研究旨在评估某些NETs成分对母马子宫内膜纤维化的体外作用，并确定其与组织病理学或发情周期的关系。将子宫内膜外植体与NETs成分（ELA、CAT、MPO或催产素）一起孵育。在卵泡期和黄体中期子宫内膜（肯尼和多伊格I/IIA型和IIB/III型）中评估I型胶原蛋白（COL1）蛋白以及I型和III型（COL3）基因转录情况。所有NETs蛋白均导致COL1增加，不过子宫内膜对每种NETs蛋白酶的反应取决于发情周期和/或子宫内膜类别。由于ELA增强了COL1的产生，NETs的持续存在可能与子宫内膜炎有关。发情周期影响COL1蛋白浓度和COL3转录本，表明卵泡期可能有利于子宫内膜胶原蛋白的产生。然而，具有中度或重度病变的黄体期子宫内膜也可能易受NETs成分的纤维化影响。这些数据表明，NETs参与母马慢性子宫内膜炎可能充当假定的子宫内膜纤维化介质。
