Endocrine changes, fetal growth, and uterine artery hemodynamics after chronic estrogen suppression during the last trimester of equine pregnancy.
Abstract: Equine pregnancy is characterized by very high circulating concentrations of estrogens. The physiological roles of estrogens during equine gestation are largely unknown, although some studies suggest a role in the regulation of uterine artery hemodynamics and a relationship between low circulating estrogen concentrations and late pregnancy loss. The objectives of this experiment were to evaluate the effects of estrogen suppression on uterine artery hemodynamics and on pregnancy outcome. Estrogen synthesis was suppressed using letrozole, a potent aromatase inhibitor. Twelve pregnant mares were randomly assigned to a control (n = 6) or treatment (n = 6; 500 mg letrozole orally every 4 days) group with treatment starting at 240 days of gestation and continuing until parturition. Weekly serum samples were analyzed to determine testosterone, dehydroepiandrosterone sulfate, estradiol, estrone sulfate, progestins, and prostaglandin F2α metabolite concentrations. Ultrasonographic examinations were performed biweekly and measurements included uterine artery hemodynamics (diameter, pulsatility, and resistance indices), fetal growth using the diameter of the fetal eye, and placental evaluation using the combined thickness of the uterus and placenta. At parturition, gestational length, foal weight, and neonatal viability were determined. Letrozole suppressed estrogen synthesis during gestation by approximately 90% compared to control values. This large reduction in circulating estrogens had no effect on uterine artery hemodynamics, normal placental development, maintenance of pregnancy, or neonatal viability. However, neonates from letrozole-treated mares had lower (P < 0.05) birth weights than controls, suggesting that estrogens may play a role in fetal growth that is not mediated through regulation of uterine blood flow.
Publication Date: 2017-02-17 PubMed ID: 28203724DOI: 10.1095/biolreprod.116.140533Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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The research article investigates the effects of suppressing estrogen production during the final trimester of horse pregnancies. Specifically, the study analyzed whether lowered levels of estrogen affected the blood flow in the uterine artery, the development of the fetus and the placenta, and the health of the newborn foal. The study found that lower estrogen levels had no effect on most of these factors, except that foals born to mares treated with an estrogen inhibitor had lower birth weights.
Approach
- The study involved twelve pregnant mares, which were split into a control group and a treatment group. The latter was given letrozole, a drug that inhibits the production of estrogen, from the 240th day of their pregnancies until they gave birth.
- Throughout the experiment, weekly serum samples were collected from the mares to track their levels of various hormones, including testosterone, dehydroepiandrosterone sulfate, estradiol, estrone sulfate, progestins, and prostaglandin F2α metabolite.
- The researchers also conducted biweekly ultrasonic examinations to measure aspects of the uterine artery’s functioning, the growth of the fetus (measured via the size of its eye), and the combined thickness of the uterus and placenta — an indicator of placental health.
- At birth, the researchers recorded the length of gestation, the foal’s weight, and its viability at birth.
Findings
- The use of letrozole resulted in a notable reduction of estrogen synthesis — about 90% compared to the levels in the control group.
- This significant decrease in estrogen levels did not affect uterine artery hemodynamics, normal placental development, duration of pregnancy, or neonatal viability. In other words, the horse’s bodies adequately compensated for the lower estrogen levels when it came to essentially all aspects of pregnancy and giving birth.
- The only difference observed was in relation to birth weight. Foals born to mares that had received letrozole had lower birth weights than those born to the control group. This suggests that estrogens play a role in fetal growth that isn’t necessarily tied to regulating blood flow to the uterus.
Significance
- The research provides insights into the role of estrogens in equine pregnancies, a subject that had not been fully understood prior to this study.
- This work specifically contributes to our understanding of how estrogen influences fetal growth and might be useful in the prevention of late pregnancy losses, often linked to low estrogen levels.
- More broadly, this experiment opens up potential areas for further research and may have implications not only for veterinary medicine, but also for human reproductive health.
Cite This Article
APA
Esteller-Vico A, Ball BA, Troedsson MHT, Squires EL.
(2017).
Endocrine changes, fetal growth, and uterine artery hemodynamics after chronic estrogen suppression during the last trimester of equine pregnancy.
Biol Reprod, 96(2), 414-423.
https://doi.org/10.1095/biolreprod.116.140533 Publication
Researcher Affiliations
- Reproduction Laboratory, Maxwell H. Gluck Equine Research Center, Lexington, Kentucky, USA.
- Department of Veterinary Science, Gluck Equine Research Center, Lexington, USA.
- Department of Veterinary Science, Gluck Equine Research Center, Lexington, USA.
- Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky, USA.
MeSH Terms
- Animals
- Aromatase Inhibitors / administration & dosage
- Aromatase Inhibitors / pharmacology
- Estrogens / metabolism
- Female
- Fetal Development / physiology
- Hemodynamics / drug effects
- Horses / physiology
- Letrozole
- Nitriles / pharmacology
- Pregnancy
- Pregnancy, Animal / physiology
- Triazoles / pharmacology
- Uterine Artery / physiology
- Uterus / blood supply
Citations
This article has been cited 7 times.- Schuler G, Fürbass R, Klisch K. Placental contribution to the endocrinology of gestation and parturition. Anim Reprod 2018 Jul-Sep;15(Suppl 1):822-842.
- Haneda S, Dini P, Esteller-Vico A, Scoggin KE, Squires EL, Troedsson MH, Daels P, Nambo Y, Ball BA. Estrogens Regulate Placental Angiogenesis in Horses. Int J Mol Sci 2021 Nov 9;22(22).
- Starič J, Hodnik JJ. Biochemical Bone Markers During the Transition Period Are Not Influenced by Parenteral Treatment With a High Dose of Cholecalciferol but Can Predict Milk Fever in Dairy Cows. Front Vet Sci 2020;7:591324.
- Hinton A Jr, Neikirk K, Le H, Harris C, Oliver A, Martin P, Gaye A. Estrogen receptors in mitochondrial metabolism: age-related changes and implications for pregnancy complications. Aging Adv 2024 Dec;1(2):154-171.
- Adel O, El-Sherbiny HR, Shahat AM, Ismail ST. Effect of a single dose of letrozole on ejaculation time, semen quality, and testicular hemodynamics in goat bucks subjected to heat stress. Vet Res Commun 2024 Dec;48(6):3941-3952.
- Miller JL, Reddy A, Harman RM, Van de Walle GR. A xenotransplantation mouse model to study physiology of the mammary gland from large mammals. PLoS One 2024;19(2):e0298390.
- Piotrowska-Tomala KK, Jonczyk AW, Szóstek-Mioduchowska A, Hojo T, Żebrowska E, Katila T, Ferreira-Dias G, Skarzynski DJ. Intrauterine devices influence prostaglandin secretion by equine uterus: in vitro and in vivo studies. BMC Vet Res 2024 Feb 3;20(1):46.
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