Estrogens regulate placental angiogenesis in horses

Shingo Haneda, Pouya Dini, Alejandro Esteller-Vico, Kirsten E. Scoggin, Edward L. Squires, Mats H. Troedsson, Peter Daels, Yasuo Nambo, Barry A. Ball

Research output: Contribution to journalArticlepeer-review

Abstract

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 hor-mone 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 con-centrations, and tended to reduce the weight of the fetus (p <0.1). Moreover, the gene expression of CYP17A1 was increased, and the expression of androgen receptor was decreased in the D120 chori-oallantois (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 17β-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.

Original languageEnglish
Article number12116
JournalInternational Journal of Molecular Sciences
Volume22
Issue number22
DOIs
StatePublished - Nov 1 2021

Bibliographical note

Funding Information:
This work was supported by the Albert G. Clay Endowment and the Clay Visiting Scholar Fellowship of the University of Kentucky.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • 17β-estradiol
  • Angiogenesis
  • Chorioallantois
  • Equine
  • Estrogen
  • Letrozole
  • Placenta
  • Placental development
  • Pregnancy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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