Estrogens Regulate Placental Angiogenesis in Horses

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 (<...

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Autores principales: Shingo Haneda, Pouya Dini, Alejandro Esteller-Vico, Kirsten E. Scoggin, Edward L. Squires, Mats H. Troedsson, Peter Daels, Yasuo Nambo, Barry A. Ball
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spelling oai:doaj.org-article:b5250dc5ce064502b62427bb1f23a4052021-11-25T17:53:30ZEstrogens Regulate Placental Angiogenesis in Horses10.3390/ijms2222121161422-00671661-6596https://doaj.org/article/b5250dc5ce064502b62427bb1f23a4052021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12116https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067A 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 (<i>Equus caballus</i>) 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 (<i>p</i> < 0.1). Moreover, the gene expression of <i>CYP17A1</i> 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 (<i>p</i> = 0.07). In addition, expression of a subset of angiogenic genes, such as <i>ANGPT1</i>, <i>VEGF</i>, and <i>NOS2</i>, were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of <i>ANGPT1</i> and <i>VEGF</i> 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.Shingo HanedaPouya DiniAlejandro Esteller-VicoKirsten E. ScogginEdward L. SquiresMats H. TroedssonPeter DaelsYasuo NamboBarry A. BallMDPI AGarticlechorioallantoisplacentaletrozoleangiogenesisplacental developmentestrogenBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12116, p 12116 (2021)
institution DOAJ
collection DOAJ
language EN
topic chorioallantois
placenta
letrozole
angiogenesis
placental development
estrogen
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle chorioallantois
placenta
letrozole
angiogenesis
placental development
estrogen
Biology (General)
QH301-705.5
Chemistry
QD1-999
Shingo Haneda
Pouya Dini
Alejandro Esteller-Vico
Kirsten E. Scoggin
Edward L. Squires
Mats H. Troedsson
Peter Daels
Yasuo Nambo
Barry A. Ball
Estrogens Regulate Placental Angiogenesis in Horses
description 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 (<i>Equus caballus</i>) 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 (<i>p</i> < 0.1). Moreover, the gene expression of <i>CYP17A1</i> 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 (<i>p</i> = 0.07). In addition, expression of a subset of angiogenic genes, such as <i>ANGPT1</i>, <i>VEGF</i>, and <i>NOS2</i>, were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of <i>ANGPT1</i> and <i>VEGF</i> 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.
format article
author Shingo Haneda
Pouya Dini
Alejandro Esteller-Vico
Kirsten E. Scoggin
Edward L. Squires
Mats H. Troedsson
Peter Daels
Yasuo Nambo
Barry A. Ball
author_facet Shingo Haneda
Pouya Dini
Alejandro Esteller-Vico
Kirsten E. Scoggin
Edward L. Squires
Mats H. Troedsson
Peter Daels
Yasuo Nambo
Barry A. Ball
author_sort Shingo Haneda
title Estrogens Regulate Placental Angiogenesis in Horses
title_short Estrogens Regulate Placental Angiogenesis in Horses
title_full Estrogens Regulate Placental Angiogenesis in Horses
title_fullStr Estrogens Regulate Placental Angiogenesis in Horses
title_full_unstemmed Estrogens Regulate Placental Angiogenesis in Horses
title_sort estrogens regulate placental angiogenesis in horses
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/b5250dc5ce064502b62427bb1f23a405
work_keys_str_mv AT shingohaneda estrogensregulateplacentalangiogenesisinhorses
AT pouyadini estrogensregulateplacentalangiogenesisinhorses
AT alejandroestellervico estrogensregulateplacentalangiogenesisinhorses
AT kirstenescoggin estrogensregulateplacentalangiogenesisinhorses
AT edwardlsquires estrogensregulateplacentalangiogenesisinhorses
AT matshtroedsson estrogensregulateplacentalangiogenesisinhorses
AT peterdaels estrogensregulateplacentalangiogenesisinhorses
AT yasuonambo estrogensregulateplacentalangiogenesisinhorses
AT barryaball estrogensregulateplacentalangiogenesisinhorses
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