Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium
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...
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MDPI AG
2021-09-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Maria Rosa Rebordão |
| collection | DOAJ |
| description | 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<sub>2α</sub>-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<sub>2α</sub> (EIA) and transcription (qPCR) of its synthases (<i>PTGS2</i>, <i>AKR1C3</i>) and receptor (<i>PTGFR</i>) genes were evaluated. PGF<sub>2α</sub> and <i>PTGFR</i> were influenced by endometrial category and estrous cycle phase. In FLP endometrium, NETs enzymes induced both high PGF<sub>2α</sub> 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<sub>2α</sub> pathway, as well as fibrosis outcome on endometrium challenged by NETs enzymes. |
| first_indexed | 2024-03-10T07:58:35Z |
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| institution | Directory Open Access Journal |
| issn | 2076-2615 |
| language | English |
| last_indexed | 2024-03-10T07:58:35Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-e926bdc011fa4701a8d70d916273e2f92023-11-22T11:42:51ZengMDPI AGAnimals2076-26152021-09-01119261510.3390/ani11092615Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare EndometriumMaria Rosa Rebordão0Ana Amaral1Carina Fernandes2Elisabete Silva3Karolina Lukasik4Anna Szóstek-Mioduchowska5Pedro Pinto-Bravo6António Galvão7Dariusz J. Skarzynski8Graça Ferreira-Dias9CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalDepartment of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, PolandDepartment of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, PolandPolytechnic Institute of Coimbra, College of Agriculture, 3045-601 Coimbra, PortugalDepartment of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, PolandDepartment of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, PolandCIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, 1300-477 Lisboa, PortugalEndometrosis, 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<sub>2α</sub>-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<sub>2α</sub> (EIA) and transcription (qPCR) of its synthases (<i>PTGS2</i>, <i>AKR1C3</i>) and receptor (<i>PTGFR</i>) genes were evaluated. PGF<sub>2α</sub> and <i>PTGFR</i> were influenced by endometrial category and estrous cycle phase. In FLP endometrium, NETs enzymes induced both high PGF<sub>2α</sub> 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<sub>2α</sub> pathway, as well as fibrosis outcome on endometrium challenged by NETs enzymes.https://www.mdpi.com/2076-2615/11/9/2615neutrophil extracellular trapsfibrosisendometriumendometrosishorsePGF<sub>2α</sub> |
| spellingShingle | 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 Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium Animals neutrophil extracellular traps fibrosis endometrium endometrosis horse PGF<sub>2α</sub> |
| title | Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium |
| title_full | Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium |
| title_fullStr | Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium |
| title_full_unstemmed | Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium |
| title_short | Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF<sub>2α</sub> Pathway in the Mare Endometrium |
| title_sort | enzymes present in neutrophil extracellular traps may stimulate the fibrogenic pgf sub 2α sub pathway in the mare endometrium |
| topic | neutrophil extracellular traps fibrosis endometrium endometrosis horse PGF<sub>2α</sub> |
| url | https://www.mdpi.com/2076-2615/11/9/2615 |
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