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Home / Equine Research Bank / Int J Mol Sci / Estrogens Regulate Placental Angiogenesis in Horses.
International journal of molecular sciences2021; 22(22); 12116; doi: 10.3390/ijms222212116

Estrogens Regulate Placental Angiogenesis in Horses.

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 () 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 ( < 0.1). Moreover, the gene expression of 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 ( = 0.07). In addition, expression of a subset of angiogenic genes, such as , , and , were altered in the CAs of letrozole-treated mares. We further demonstrated that 17β-estradiol increases the expression of and 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.
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Publication Date: 2021-11-09 PubMed ID: 34829994PubMed Central: PMC8621320DOI: 10.3390/ijms222212116Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores how estrogens, a hormone family, regulate the growth and expansion of the vascular network in horse placentas, which is necessary for placental function. The researchers used an aromatase inhibitor, letrozole, to decrease estrogen levels during the first trimester of gestation, leading to a decrease in circulatory estrone sulfate and an increase in testosterone and androstenedione, which has affected fetal weight and influenced the expression of certain genes. The results also suggested a decrease in vessel numbers and alterations in the expression of angiogenic genes. In vitro testing further supported that 17β-estradiol, a form of estrogen, increases angiogenic activity of equine endothelial cells, indicating that estrogens are essential for placental vasculogenesis.

Objective and Hypothesis

  • The researchers aimed to investigate the role of estrogens in regulating placental angiogenesis, the process of forming new blood vessels, in horses.
  • The researchers hypothesized that the growth and expansion of the placental vascular network in horses is regulated by estrogens. These hormones have a high concentration in circulation during gestation.

Methodology

  • The researchers administered letrozole, an aromatase inhibitor, to horses during the first trimester of gestation (from day 30 to day 118). This drug is known to lower estrogen levels.
  • The impacts of letrozole on circulatory estrone sulfate, testosterone and androstenedione concentrations were measured.
  • The gene expressions of certain placental development-related genes were also examined.

Findings

  • Letrozole administration led to decreased circulatory estrone sulfate concentrations and increased circulatory testosterone and androstenedione concentrations.
  • The fetus weight was reduced, which suggests that lowered estrogen concentration might have an adverse impact on fetal development.
  • The expression of certain genes related to placental development was altered. For instance, the gene expression of was increased, and the expression of the androgen receptor was decreased.
  • Moreover, the number of vessels in the placental structures was found to have a tendency to decrease.
  • Some angiogenic genes expression was altered, suggesting that estrogen levels influence these genes and thus, angiogenesis.

Conclusion

  • In vitro experiments further demonstrated that 17β-estradiol, a type of estrogen, stimulates the expression of key genes and promotes the angiogenic activity of equine endothelial cells.
  • The results of the study support the hypothesis that estrogens regulate placental angiogenesis in horses. When estrogen levels were suppressed, an impaired placental vascular network was observed, suggesting an estrogen-dependent vasculogenesis mechanism in equine placentas during the first trimester.

Cite This Article

APA
Haneda S, Dini P, Esteller-Vico A, Scoggin KE, Squires EL, Troedsson MH, Daels P, Nambo Y, Ball BA. (2021). Estrogens Regulate Placental Angiogenesis in Horses. Int J Mol Sci, 22(22), 12116. https://doi.org/10.3390/ijms222212116

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 22
Issue: 22
PII: 12116

Researcher Affiliations

Haneda, Shingo
  • Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
Dini, Pouya
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
  • Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
Esteller-Vico, Alejandro
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
  • Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Scoggin, Kirsten E
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Squires, Edward L
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Troedsson, Mats H
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Daels, Peter
  • Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Nambo, Yasuo
  • Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Japan.
Ball, Barry A
  • Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.

MeSH Terms

  • Androstenedione / genetics
  • Angiopoietin-1 / genetics
  • Animals
  • Aromatase / genetics
  • Estrogens / genetics
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Horses / genetics
  • Horses / growth & development
  • Letrozole / pharmacology
  • Maternal-Fetal Relations / drug effects
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / genetics
  • Placenta / blood supply
  • Placenta / drug effects
  • Pregnancy
  • Pregnancy Trimester, First
  • Receptors, Androgen / genetics
  • Steroid 17-alpha-Hydroxylase / genetics
  • Testosterone / genetics
  • Vascular Endothelial Growth Factor A / genetics

Grant Funding

  • the Albert G. Clay Endowment and the Clay Visiting Scholar Fellowship of the University of Kentucky

Conflict of Interest Statement

The authors have no conflict of interest.

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Citations

This article has been cited 6 times.
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