{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:53:00Z","timestamp":1787237580557,"version":"build-2736575974"},"reference-count":54,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Albert G. Clay Endowment and the Clay Visiting Scholar Fellowship of the University of Kentucky","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A sufficient vascular network within the feto-maternal interface is necessary for placental function. Several pregnancy abnormalities have been associated with abnormal vascular formations in the placenta. We hypothesized that growth and expansion of the placental vascular network in the equine (Equus caballus) placenta is regulated by estrogens (estrogen family hormones), a hormone with a high circulating concentration during equine gestation. Administration of letrozole, a potent and specific inhibitor of aromatase, during the first trimester (D30 to D118), decreased circulatory estrone sulfate concentrations, increased circulatory testosterone and androstenedione concentrations, and tended to reduce the weight of the fetus (p &lt; 0.1). Moreover, the gene expression of CYP17A1 was increased, and the expression of androgen receptor was decreased in the D120 chorioallantois (CA) of letrozole-treated mares in comparison to that of the control mares. We also found that at D120, the number of vessels tended to decrease in the CAs with letrozole treatment (p = 0.07). In addition, expression of a subset of angiogenic genes, such as ANGPT1, VEGF, and NOS2, were altered in the CAs of letrozole-treated mares. We further demonstrated that 17\u03b2-estradiol increases the expression of ANGPT1 and VEGF and increases the angiogenic activity of equine endothelial cells in vitro. Our results from the estrogen-suppressed group demonstrated an impaired placental vascular network, suggesting an estrogen-dependent vasculogenesis in the equine CA during the first trimester.<\/jats:p>","DOI":"10.3390\/ijms222212116","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T12:46:23Z","timestamp":1636461983000},"page":"12116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Estrogens Regulate Placental Angiogenesis in Horses"],"prefix":"10.3390","volume":"22","author":[{"given":"Shingo","family":"Haneda","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5553-5967","authenticated-orcid":false,"given":"Pouya","family":"Dini","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA"},{"name":"Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Esteller-Vico","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA"},{"name":"Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1348-641X","authenticated-orcid":false,"given":"Kirsten E.","family":"Scoggin","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward L.","family":"Squires","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats H.","family":"Troedsson","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0307","authenticated-orcid":false,"given":"Peter","family":"Daels","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Nambo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0502-0276","authenticated-orcid":false,"given":"Barry A.","family":"Ball","sequence":"additional","affiliation":[{"name":"Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3233\/JAD-160303","article-title":"The role of capillaries in the lesser ailments of old age and in Alzheimer\u2019s disease and vascular dementia: The potential of pro-therapeutic angiogenesis","volume":"54","author":"Ambrose","year":"2016","journal-title":"J. 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