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Theriogenology2025; 252; 117758; doi: 10.1016/j.theriogenology.2025.117758

Influence of follicular size, plasma progesterone, and estradiol benzoate administration on endometrial edema onset and duration in mares.

Abstract: Endometrial edema is an ultrasonographic sign of estrus in mares and is positively associated with fertility. This study aimed to evaluate the influence of follicular size, systemic progesterone (P4), and exogenous estradiol benzoate (EB) on the onset and duration of endometrial edema. In Experiment 1, anestrus (n = 4) and diestrus mares (n = 4) received 4 mg of EB intramuscularly; edema scores and plasma P4 were monitored over four days. In a complementary group (n = 5), mares were monitored until ovulation, then administered 4 mg of EB and examined every 12 h for 48 h. In Experiment 2, mares (n = 9) received PGFα and were categorized based on follicle size (<25 mm or >25 mm) to assess effects on edema onset. In Experiment 3, mares (n = 13) received PGFα alone or PGFα plus EB to evaluate combined treatment effects. Anestrus mares (P4 <1 ng/mL) showed maximal edema at 24 h post-EB, resolving by day 4. Diestrus mares did not develop edema. In the OV group, edema peaked at 24 h post-EB but declined significantly by 36 h (p < 0.05), concurrent with a P4 increase from 2.2 ± 0.3 to 3.6 ± 0.6 ng/mL (p < 0.01). Follicle size tended to influence the interval to ovulation (9.4 ± 2.2 vs. 6.0 ± 2.1 days, p = 0.052) and significantly affected the total number of edema days (7 vs. 4.5, p < 0.05). Edema developed despite the presence of only small follicles, and EB at PGFα did not accelerate onset. Overall, edema dynamics appear to be progesterone-driven, and follicle size may affect estrus duration and time to OV.
Publication Date: 2025-11-15 PubMed ID: 41273966DOI: 10.1016/j.theriogenology.2025.117758Google Scholar: Lookup
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  • Journal Article
  • Clinical Trial
  • Veterinary

Summary

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Overview

  • This study investigates how follicular size, progesterone levels, and administration of estradiol benzoate influence the timing and duration of endometrial edema, an ultrasound indicator of estrus and fertility, in mares.

Background

  • Endometrial edema in mares is a visible swelling of the uterine lining that can be detected via ultrasound and is strongly linked to estrus (the mare’s fertile period) and reproductive success.
  • Understanding the hormonal and physiological factors affecting the appearance and persistence of endometrial edema can improve fertility management in mares.
  • Two important hormones studied here are progesterone (P4), which is generally higher during diestrus (non-fertile phase), and estradiol benzoate (EB), an estrogen compound that can induce estrus signs when administered.
  • Follicular size on the ovary is another factor thought to influence the estrus cycle and thus may affect edema characteristics.

Research Objectives

  • To determine how systemic progesterone levels and follicular size affect the onset and duration of endometrial edema in mares.
  • To assess whether administering exogenous estradiol benzoate (EB) influences the timing and intensity of endometrial edema.
  • To analyze whether the combination of prostaglandin F2 alpha (PGFα) treatment with EB alters the onset of endometrial edema relative to PGFα alone.

Experimental Design

  • Experiment 1:
    • Anestrus mares (non-cycling, low progesterone) and diestrus mares (high progesterone phase) received 4 mg EB intramuscularly.
    • Edema scores and blood plasma progesterone were monitored for 4 days to track onset and duration of edema.
    • A complementary group of mares was monitored until ovulation, then given EB and examined bi-daily for 48 hours.
  • Experiment 2:
    • Mares were treated with PGFα to induce luteolysis (regression of the corpus luteum) and grouped by follicular size: smaller than 25 mm or larger than 25 mm.
    • The effect of follicle size on when edema began was measured.
  • Experiment 3:
    • Mares received PGFα alone or PGFα combined with EB.
    • This experiment tested if EB given alongside PGFα would accelerate the onset of endometrial edema compared to PGFα alone.

Key Findings

  • Effect of Estradiol Benzoate in Different Hormonal States
    • Anestrus mares with low progesterone (<1 ng/mL) developed maximal endometrial edema 24 hours after EB administration, which resolved by day 4.
    • Diestrus mares, which had higher progesterone, did not develop edema following EB administration, highlighting progesterone’s antagonistic effect.
  • Edema Dynamics Around Ovulation
    • Mares given EB at ovulation showed edema peaking at 24 hours but a significant decrease by 36 hours, coinciding with a progesterone increase from 2.2 to 3.6 ng/mL.
    • This suggests rising progesterone levels lead to the reduction of endometrial edema post-estrus.
  • Influence of Follicle Size
    • Mares with larger follicles (>25 mm) had a shorter interval to ovulation (around 6 days) compared to those with smaller follicles (<25 mm, about 9.4 days), though this difference was at the border of statistical significance (p=0.052).
    • Follicle size significantly affected the total duration of endometrial edema, with larger follicles associated with shorter edema periods (4.5 vs. 7 days).
    • Notably, endometrial edema still developed even when only small follicles were present, indicating follicle size alone does not prevent edema formation.
  • Effect of Combining PGFα and EB
    • Adding EB alongside PGFα did not accelerate the onset of endometrial edema compared to treatment with PGFα alone.
    • This suggests that EB administration does not strongly influence the timing of edema initiation in the presence of luteolysis induced by PGFα.

Conclusions

  • Endometrial edema onset and duration are primarily driven by progesterone levels: low progesterone permits the development of edema, while higher progesterone levels inhibit it.
  • Although follicle size impacts the duration of estrus and timing of ovulation, it does not prevent edema from developing entirely.
  • Exogenous estradiol benzoate can induce endometrial edema in low-progesterone mares but does not speed up edema onset when combined with PGFα.
  • These findings help clarify the hormonal and physiological factors controlling endometrial changes in the mare, which can inform better reproductive management and fertility prediction strategies.

Cite This Article

APA
Sala-Ayala L, Cuervo-Arango J, Martínez Boví R. (2025). Influence of follicular size, plasma progesterone, and estradiol benzoate administration on endometrial edema onset and duration in mares. Theriogenology, 252, 117758. https://doi.org/10.1016/j.theriogenology.2025.117758

Publication

ISSN: 1879-3231
NlmUniqueID: 0421510
Country: United States
Language: English
Volume: 252
Pages: 117758
PII: S0093-691X(25)00484-4

Researcher Affiliations

Sala-Ayala, Laura
  • Equine Fertility Group, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Spain. Electronic address: laura.salaayala@gmail.com.
Cuervo-Arango, Juan
  • Equine Fertility Group, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Spain.
Martínez Boví, Rebeca
  • Equine Fertility Group, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, Alfara del Patriarca, Spain.

MeSH Terms

  • Animals
  • Female
  • Progesterone / blood
  • Horses
  • Estradiol / analogs & derivatives
  • Estradiol / administration & dosage
  • Estradiol / pharmacology
  • Ovarian Follicle / anatomy & histology
  • Ovarian Follicle / physiology
  • Ovarian Follicle / drug effects
  • Edema / veterinary
  • Edema / chemically induced
  • Endometrium / drug effects
  • Endometrium / pathology
  • Horse Diseases / chemically induced
  • Dinoprost / pharmacology
  • Dinoprost / administration & dosage

Conflict of Interest Statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Citations

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