{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T03:07:19Z","timestamp":1771297639280,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/ CVT\/276\/2013; UIDB\/00276\/2020; PTDC\/CVT-REP\/4202\/2014"],"award-info":[{"award-number":["UID\/ CVT\/276\/2013; UIDB\/00276\/2020; PTDC\/CVT-REP\/4202\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014434","name":"Narodowa Agencja Wymiany Akademickiej","doi-asserted-by":"publisher","award":["No. PPN\/BIL\/2018\/1\/00250\/U\/0001"],"award-info":[{"award-number":["No. PPN\/BIL\/2018\/1\/00250\/U\/0001"]}],"id":[{"id":"10.13039\/501100014434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>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 PGF2\u03b1-pathway activation. Kenney and Doig\u2019s 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 PGF2\u03b1 (EIA) and transcription (qPCR) of its synthases (PTGS2, AKR1C3) and receptor (PTGFR) genes were evaluated. PGF2\u03b1 and PTGFR were influenced by endometrial category and estrous cycle phase. In FLP endometrium, NETs enzymes induced both high PGF2\u03b1 production and\/or PTGFR transcription. In MLP type I\/IIA tissues, down-regulation of PTGFR transcripts occurred. However, in MLP type IIB\/III endometrium, high levels of PTGFR transcripts were induced by NETs enzymes. As PGF2\u03b1-pathway activation facilitates fibrogenesis in other tissues, PGF2\u03b1 may be involved in endometrosis pathogenesis. In the mare, the endocrine microenvironment of healthy and pathological endometrium might modulate the PGF2\u03b1 pathway, as well as fibrosis outcome on endometrium challenged by NETs enzymes.<\/jats:p>","DOI":"10.3390\/ani11092615","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T10:59:12Z","timestamp":1630925952000},"page":"2615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Enzymes Present in Neutrophil Extracellular Traps May Stimulate the Fibrogenic PGF2\u03b1 Pathway in the Mare Endometrium"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4389-445X","authenticated-orcid":false,"given":"Maria Rosa","family":"Rebord\u00e3o","sequence":"first","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Polytechnic Institute of Coimbra, College of Agriculture, 3045-601 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-262X","authenticated-orcid":false,"given":"Ana","family":"Amaral","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"given":"Carina","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2332-7642","authenticated-orcid":false,"given":"Elisabete","family":"Silva","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2476-8818","authenticated-orcid":false,"given":"Karolina","family":"Lukasik","sequence":"additional","affiliation":[{"name":"Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, Poland"}]},{"given":"Anna","family":"Sz\u00f3stek-Mioduchowska","sequence":"additional","affiliation":[{"name":"Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9442-7539","authenticated-orcid":false,"given":"Pedro","family":"Pinto-Bravo","sequence":"additional","affiliation":[{"name":"Polytechnic Institute of Coimbra, College of Agriculture, 3045-601 Coimbra, Portugal"}]},{"given":"Ant\u00f3nio","family":"Galv\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-3560","authenticated-orcid":false,"given":"Dariusz J.","family":"Skarzynski","sequence":"additional","affiliation":[{"name":"Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of PAS, 10-748 Olsztyn, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-6513","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Ferreira-Dias","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centro de Investiga\u00e7\u00e3o Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00430-009-0121-x","article-title":"The clinical value of neutrophil extracellular traps","volume":"198","author":"Margraf","year":"2009","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1083\/jcb.201203170","article-title":"Neutrophil extracellular traps: Is immunity the second function of chromatin?","volume":"198","author":"Brinkmann","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1214e6","DOI":"10.1182\/blood-2011-07-364604","article-title":"Killing by neutrophil extracellular traps: Fact or folklore?","volume":"119","author":"Menegazzi","year":"2012","journal-title":"Blood"},{"key":"ref_5","first-page":"pe11","article-title":"Unconventional roles of the NADPH oxidase: Signaling, ion homeostasis, and cell death","volume":"379","author":"Steinberg","year":"2007","journal-title":"Sci. STKE"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1189\/jlb.0910538","article-title":"The paradox of the neutrophil\u2019s role in tissue injury","volume":"89","author":"Segel","year":"2011","journal-title":"J. Leukoc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/1476-9255-7-45","article-title":"Protein targets of inflammatory serine proteases and cardiovascular disease","volume":"7","author":"Sharony","year":"2010","journal-title":"J. Inflamm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/hr.2010.58","article-title":"Neutrophil elastase inhibitor prevents ischemic brain damage via reduction of vasogenic edema","volume":"33","author":"Ikegame","year":"2010","journal-title":"Hypertens. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jcf.2015.03.003","article-title":"Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy","volume":"14","author":"Cantin","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1089\/ars.2014.6108","article-title":"Myeloperoxidase\u2013Hepatocyte\u2013Stellate Cell Cross Talk Promotes Hepatocyte Injury and Fibrosis in Experimental Nonalcoholic Steatohepatitis","volume":"23","author":"Pulli","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4359","article-title":"Neutrophil extracellular traps promote differentiation and function of fibroblasts","volume":"233","author":"Chrysanthopoulou","year":"2014","journal-title":"J. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S0024-3205(02)02299-3","article-title":"Complex cytokine regulation of tissue fibrosis","volume":"72","author":"Atamas","year":"2002","journal-title":"Life Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1038\/nm.2066","article-title":"Prostaglandin F2\u03b1 receptor signaling facilitates bleomycin induced pulmonary fibrosis independently of transforming growth factor-\u03b2","volume":"15","author":"Oga","year":"2009","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/ATVBAHA.110.207449","article-title":"Prostaglandins and inflammation","volume":"31","author":"Ricciotti","year":"2011","journal-title":"Arter. Thromb Vasc Biol."},{"key":"ref_15","first-page":"65","article-title":"A postgenomic integrated view of prostaglandins in reproduction: Implications for other body systems","volume":"59","author":"Fortier","year":"2008","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.bbrc.2005.08.152","article-title":"Coupling between cyclooxygenases and terminal prostanoid synthases","volume":"338","author":"Ueno","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.pharmthera.2004.06.003","article-title":"Pharmacology and signaling of prostaglandin receptors: Multiple roles in inflammation and immune modulation","volume":"103","author":"Hata","year":"2004","journal-title":"Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Aihara, K., Handa, T., Oga, T., Watanabe, K., Tanizawa, K., Ikezoe, K., Taguchi, Y., Sato, H., Chin, K., and Nagai, S. (2013). Clinical relevance of plasma prostaglandin F2\u03b1 metabolite concentrations in patients with idiopathic pulmonary fibrosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066017"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2492\/inflammregen.33.109","article-title":"erRoles of eicosanoids in pulmonary fibrosis","volume":"33","author":"Oga","year":"2013","journal-title":"Inflamm. Regen."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1038\/nm1209-1360","article-title":"Beyond TGF-\u03b2: A prostaglandin promotes fibrosis","volume":"15","author":"Olman","year":"2009","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.biocel.2012.03.013","article-title":"The Prostaglandin F2\u03b1 facilitates collagen synthesis in cardiac fibroblasts via an F-prostanoid receptor\/protein kinase C\/Rho kinase pathway independent of transforming growth factor \u03b21","volume":"44","author":"Ding","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s00109-013-1119-9","article-title":"FP-receptor gene silencing ameliorates myocardial fibrosis and protects from diabetic cardiomyopathy","volume":"92","author":"Ding","year":"2014","journal-title":"J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/art.37767","article-title":"Alpha2-Antiplasmin Regulates the Development of dermal fibrosis in mice by Prostaglandin F2\u03b1 synthesis through adipose triglyceride Lipase\/Calcium-independent phospholipase","volume":"65","author":"Kanno","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1002\/art.37996","article-title":"Stimulation of fibrotic processes by the infrapatellar fat pad in cultured synoviocytes from patients with osteoarthritis: A possible role for prostaglandin f2\u03b1","volume":"65","author":"Wei","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.anireprosci.2008.03.019","article-title":"The equine endometrosis: New insights into the pathogenesis","volume":"111","author":"Hoffmann","year":"2009","journal-title":"Anim. Reprod. Sci."},{"key":"ref_26","first-page":"1717","article-title":"Complimentary Diagnostic Tools for Endometrosis in Biopsies of Mares with Clinical Subfertility","volume":"48","author":"Rojas","year":"2020","journal-title":"Acta Sci. Vet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jri.2014.08.003","article-title":"Neutrophil extracellular traps formation by bacteria causing endometritis in the mare","volume":"106","author":"Carneiro","year":"2014","journal-title":"J. Reprod. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.theriogenology.2012.03.024","article-title":"mRNA transcription of prostaglandin synthases and their products in the equine endometrium in the course of fibrosis","volume":"78","author":"Siemieniuch","year":"2012","journal-title":"Theriogenology"},{"key":"ref_29","unstructured":"Ginther, O.J. (1992). Characteristics of the ovulatory season. Reproductive Biology of the Mare: Basic and Applied Aspects, Equiservices. [2nd ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1071\/RD06159","article-title":"Caspase-3 mediated apoptosis and cell proliferation in the equine endometrium during the oestrous cycle","volume":"19","author":"Monteiro","year":"2007","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.theriogenology.2007.05.050","article-title":"Relationships between uterine culture, ccytology and pregnancy rates in a Thoroughbred practice","volume":"68","author":"Riddle","year":"2007","journal-title":"Theriogenology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Urban, C., Ermert, D., Schmid, M., Abu-Abed, U., Goosmann, C., Nacken, W., Brinkmann, V., Jungblut, P.R., and Zychlinsky, A. (2009). Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000639"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1165\/rcmb.2011-0380OC","article-title":"Influence of DNA on the activities and inhibition of neutrophil serine proteases in cystic fibrosis sputum","volume":"47","author":"Dubois","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.biocel.2008.03.003","article-title":"Proteases and Cystic Fibrosis","volume":"40","author":"Voynow","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/sj.bjp.0704089","article-title":"Endothelium-dependent relaxation induced by cathepsin G in porcine pulmonary arteries","volume":"133","author":"Glusa","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.bbrc.2004.10.049","article-title":"Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: An additional mechanism to subendothelium oxidation","volume":"325","author":"Boudjeltia","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.theriogenology.2014.01.011","article-title":"High concentrations of myeloperoxidase in the equine uterus as an indicator of endometritis","volume":"81","author":"Ponthier","year":"2014","journal-title":"Theriogenology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.theriogenology.2005.05.034","article-title":"Endometritis in the mare: A diagnostic study comparing cultures from swab and biopsy","volume":"64","author":"Nielsen","year":"2005","journal-title":"Theriogenology"},{"key":"ref_39","unstructured":"Morrow, D.A. (1986). Equine endometrial biopsy. Current Therapy Theriogenology, WB Saunders."},{"key":"ref_40","first-page":"79","article-title":"Impairment of the interleukin system in equine endometrium during the course of endometrosis","volume":"89","author":"Lukasik","year":"2013","journal-title":"Biol. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1600-0897.2007.00548.x","article-title":"Endometrial explant culture for characterizing equine endometritis","volume":"59","author":"Nash","year":"2008","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1530\/JOE-13-0185","article-title":"Ovarian steroids affect prostaglandin production in equine endometrial cells in vitro","volume":"220","author":"Skarzynski","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_43","first-page":"618021","article-title":"Culture of breast tumor explants as a multicellular system for the screening of natural compounds with antineoplastic potential","volume":"2015","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.theriogenology.2016.08.028","article-title":"Expression of prostaglandin synthases, ovarian steroids and oxytocin receptors in equine endometrium during luteal maintenance induced by chronic administration of oxytocin","volume":"87","author":"Pinheiro","year":"2017","journal-title":"Theriogenology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.domaniend.2006.03.007","article-title":"Endometrial nitric oxide production and nitric oxide synthases in the equine endometrium: Relationship with microvascular density during the estrous cycle","volume":"32","author":"Mateus","year":"2007","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1095\/biolreprod.110.084699","article-title":"Is the Fas\/Fas ligand system involved in equine corpus luteum functional regression?","volume":"83","author":"Skarzynski","year":"2010","journal-title":"Biol. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e1148","DOI":"10.1093\/nar\/gks596","article-title":"Primer3\u2014New capabilities and interfaces","volume":"40","author":"Untergasser","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.theriogenology.2018.02.001","article-title":"Constituents of neutrophil extracellular traps induce in vitro collagen formation in mare endometrium","volume":"113","author":"Amaral","year":"2018","journal-title":"Theriogenology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/cmb.2005.12.1047","article-title":"Comprehensive algorithm for quantitative real-time polymerase chain reaction","volume":"12","author":"Zhao","year":"2005","journal-title":"J. Comput. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1136\/thorax.57.9.830","article-title":"Chronic obstructive pulmonary disease-part 2: Pathology and biochemistry of emphysema","volume":"57","author":"Hogg","year":"2002","journal-title":"Thorax"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.theriogenology.2020.04.040","article-title":"Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts","volume":"153","author":"Baclawska","year":"2020","journal-title":"Theriogenology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/rda.13258","article-title":"Elastase inhibition affects collagen transcription and prostaglandin secretion in mare endometrium during the estrous cycle","volume":"53","author":"Amaral","year":"2018","journal-title":"Reprod. Domest. Anim."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.domaniend.2018.10.004","article-title":"Impairment of the antifibrotic prostaglandin E2 pathway may influence neutrophil extracellular traps\u2013induced fibrosis in the mare endometrium","volume":"67","author":"Amaral","year":"2019","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"11639","DOI":"10.1021\/acs.jmedchem.0c00834","article-title":"Potent and Selective Human Prostaglandin F (FP) Receptor Antagonist (BAY-6672) for the Treatment of Idiopathic Pulmonary Fibrosis (IPF)","volume":"63","author":"Beck","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/S0002-9440(10)64092-8","article-title":"Cyclooxygenase-2 deficiency results in a loss of the anti-proliferative response to transforming growth factor in human fibrotic lung fibroblasts and promotes bleomycin-induced pulmonary fibrosis in mice","volume":"158","author":"Keerthisingam","year":"2001","journal-title":"Am. J. Pathol."},{"key":"ref_56","first-page":"208103","article-title":"Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids","volume":"2014","author":"Hojo","year":"2014","journal-title":"Mediat. Inflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1095\/biolreprod25.3.581","article-title":"Prostaglandin F2alpha in the equine endometrium: Steroid modulation and production capacities during the estrous cycle and early pregnancy","volume":"25","author":"Vernon","year":"1981","journal-title":"Biol. Reprod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.jevs.2012.11.010","article-title":"Equine breeding-induced endometritis: A review","volume":"33","author":"Woodward","year":"2013","journal-title":"J. Equine Vet. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/biolreprod\/52.monograph_series1.515","article-title":"Onset and duration of uterine inflammatory response of mares after insemination with fresh semen","volume":"1","author":"Katila","year":"1995","journal-title":"Biol. Reprod. Monogr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1530\/REP-12-0452","article-title":"Endometrial inflammatory markers of the early immune response in mares susceptible or resistant to persistent breeding-induced endometritis","volume":"145","author":"Woodward","year":"2013","journal-title":"Reproduction"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S0093-691X(99)00210-1","article-title":"Dynamics of prostaglandin secretion, intrauterine fluid and uterine clearance in reproductively normal mares and mares with delayed uterine clearance","volume":"52","author":"Cadario","year":"1999","journal-title":"Theriogenology"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Christoffersen, M., Woodward, E., Bojesen, A.M., Jacobsen, S., Petersen, M.R., Troedsson, M.H., and Lehn-Jensen, H. (2012). Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis. BMC Vet. Res., 29.","DOI":"10.1186\/1746-6148-8-41"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.anireprosci.2009.11.008","article-title":"Markers of the uterine innate immune response of the mare","volume":"119","author":"Nash","year":"2010","journal-title":"Anim. Reprod. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1095\/biolreprod.112.100776","article-title":"Plasma clearance and half-life of prostaglandin F2alpha: A comparison between mares and heifers","volume":"87","author":"Shrestha","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1530\/REP-15-0617","article-title":"Evidence for a PGF2\u03b1 auto-amplification system in the endometrium in mares","volume":"151","author":"Kozai","year":"2016","journal-title":"Reproduction"},{"key":"ref_66","first-page":"e115","article-title":"Prostaglandin E and F receptors in the uterus","volume":"1","author":"Blesson","year":"2014","journal-title":"Recept. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1071\/RD13381","article-title":"Effect of pregnancy on endometrial expression of luteolytic pathway components in the mare","volume":"27","author":"Stout","year":"2015","journal-title":"Reprod. Fertil. Dev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"36","DOI":"10.21836\/PEM20160106","article-title":"Dual effect of hormones on mare reproductive physiology and dysfunction","volume":"32","author":"Amaral","year":"2016","journal-title":"Pferdeheilkunde Equine Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jevs.2016.01.008","article-title":"A Review on the Use of Prostaglandin F2\u03b1 for Controlling the Estrous Cycle in Mares","volume":"40","author":"Coffman","year":"2016","journal-title":"J. Equine Veter- Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s00204-018-2372-z","article-title":"In vitro-to-in vivo extrapolation (IVIVE) by PBTK modeling for animal-free risk assessment approaches of potential endocrine-disrupting compounds","volume":"93","author":"Fabian","year":"2019","journal-title":"Arch. 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