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Theriogenology2017; 97; 159-169; doi: 10.1016/j.theriogenology.2017.04.031

Administration of 2.5 mg of estradiol followed by 1,500 mg of progesterone to anovulatory mares promote similar uterine morphology, hormone concentrations and molecular dynamics to those observed in cyclic mares.

Abstract: To test the hypothesis that the administration of 2.5 mg of estradiol benzoate (EB) followed by 1500 mg of long acting progesterone (LA P4) causes similar uterine changes and molecular dynamics in anovulatory mares to those observed in cyclic ones, we evaluated the changes of estrogen (ERα and ERβ) and progesterone receptors (PR) in anestrous, transitional and cyclic mares by RT-qPCR and immunohistochemistry. In addition, we evaluated uterine edema, tonus and estrogens and progesterone plasma profile. Endometrial biopsies were taken from anestrous and transitional mares immediately before EB injection, 48 h after EB administration and five days after LA P4 was given. In cyclic mares, biopsies were collected at estrus and at five days after ovulation. Similar estrogen peaks were achieved after the injection of the single EB dose between treated and cyclic groups, as well as maximum uterine edema. Uterine tone was increased to diestrus levels after administration of 1500 mg of LA P4. Changes in relative abundance of transcripts for PR, ERα and ERβ when progesterone stimulated endometrium was compared to estrogen stimulated endometrium were similar between cyclic and non-cyclic treated mares. However, apparent decreased PR in the endometrial glandular epithelium was not observed in non-cyclic mares five days after LA P4 administration as observed at five days after ovulation in cyclic mares. The protocol produced similar endometrial edema, uterine tonus and changes in relative abundance of PR, ERα and ERβ transcripts to those observed in cyclic mares during late estrus and early diestrus, as well as similar estradiol and estrogen conjugate plasma concentrations.
Publication Date: 2017-04-23 PubMed ID: 28583600DOI: 10.1016/j.theriogenology.2017.04.031Google Scholar: Lookup
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  • Controlled Clinical Trial
  • Journal Article

Summary

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The study hypothesizes and provides evidence that administering 2.5 mg of estradiol followed by 1,500 mg of a long-acting progesterone induces similar morphological and molecular changes in the uterine tracts of anovulatory mares as observed in cyclic mares.

Research Methodology

  • To test their hypothesis, the researchers examined the changes in estrogen and progesterone receptors in various reproductive states of mares (anestrous, transitional and cyclic) using RT-qPCR and immunohistochemistry.
  • The team also evaluated other physiological aspects such as uterine edema, tonus (muscle tone) and the plasma profiles of estrogens and progesterone.
  • They conducted endometrial biopsies on anestrous and transitional mares at three separate intervals – right before the injection of estradiol, 48 hours after its administration and five days after the administration of the long-acting progesterone. In cyclic mares, biopsies were taken during estrus and five days post ovulation.

Findings

  • The study found similarities in estrogen peaks between treated and cyclic groups following the injection of a single dose of estradiol. It also reported maximum uterine edema in both groups.
  • Uterine tone in the treated mares was shown to increase to diestrus levels after the administration of 1,500 mg of long-acting progesterone.
  • The study also reported comparable changes in relative abundance of progesterone receptor, estrogen receptor α and estrogen receptor β when a progesterone stimulated endometrium was compared with its estrogen-stimulated counterpart. This was observed in both cyclic and non-cyclic treated mares.
  • In non-cyclic mares however, a noticeable decrease in progesterone receptors in the endometrial glandular epithelium was not observed five days after the administration of long-acting progesterone – a phenomenon usually observed five days post ovulation in cyclic mares.

Conclusion

  • The research concluded that the administration of 2.5 mg of estradiol benzoate followed by 1,500 mg of long-acting progesterone can induce changes in uterine morphology, hormone concentrations and molecular dynamics that mirror those observed in cyclic mares. These changes include similar endometrial edema, uterine tonus and changes in relative abundance of PR, ERα and ERβ transcripts, as well as comparable estradiol and estrogen conjugate plasma concentrations.

Cite This Article

APA
Silva ESM, Ignácio FS, Fritsch SC, Zanoni DS, Pantoja JCF, Oliveira-Filho JP, Meira C. (2017). Administration of 2.5 mg of estradiol followed by 1,500 mg of progesterone to anovulatory mares promote similar uterine morphology, hormone concentrations and molecular dynamics to those observed in cyclic mares. Theriogenology, 97, 159-169. https://doi.org/10.1016/j.theriogenology.2017.04.031

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 97
Pages: 159-169
PII: S0093-691X(17)30191-7

Researcher Affiliations

Silva, E S M
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil. Electronic address: elisa_santanna@yahoo.com.br.
Ignácio, F S
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil.
Fritsch, S C
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil.
Zanoni, D S
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Veterinary Clinical Science, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil.
Pantoja, J C F
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Veterinary Hygiene and Public Health, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil.
Oliveira-Filho, J P
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Veterinary Clinical Science, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil.
Meira, C
  • UNESP - Univ. Estadual Paulista, Campus de Botucatu, Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Science, Botucatu, SP, 18618970, Brazil. Electronic address: meira@fmvz.unesp.br.

MeSH Terms

  • Animals
  • Estradiol / administration & dosage
  • Estradiol / pharmacology
  • Estrous Cycle / physiology
  • Female
  • Horses / physiology
  • Progesterone / administration & dosage
  • Progesterone / pharmacology
  • Uterus / drug effects
  • Uterus / physiology

Citations

This article has been cited 4 times.
  1. Silva ESM, Newcombe JR, Cuervo-Arango J. The Effect of Treatment with Oestradiol Benzoate on Oestrus Expression and Endometrial Oedema in Anovulatory and Cyclic Mares. Animals (Basel) 2023 Mar 5;13(5).
    doi: 10.3390/ani13050938pubmed: 36899795google scholar: lookup
  2. Segabinazzi LGTM, Andrade LRP Jr, Alvarenga MA, Dell'Aqua JA Jr, Canisso IF. Use of Intravaginal Progesterone-Releasing Device Results in Similar Pregnancy Rates and Losses to Long-Acting Progesterone to Synchronize Acyclic Embryo Recipient Mares. Vet Sci 2021 Sep 10;8(9).
    doi: 10.3390/vetsci8090190pubmed: 34564584google scholar: lookup
  3. Barbosa LA, Maran AP, de Almeida MER, Guimarães EC, Bringel B, Douglas RH, Lima TFG, da Silva ESM. Plasma Estradiol and Endometrial Edema Profile in Acyclic Mares After Single Administration of 17-β Estradiol, Estradiol Benzoate and Estradiol Cypionate. Reprod Domest Anim 2025 Aug;60(8):e70108.
    doi: 10.1111/rda.70108pubmed: 40760876google scholar: lookup
  4. Khan IU, Khairullah AR, Khan AY, Rehman AU, Mustofa I. Strategic approaches to improve equine breeding and stud farm outcomes. Vet World 2025 Feb;18(2):311-328.