Treatment of luteal phase mares with the aromatase inhibitor letrozole does not change characteristics of the estrous cycle, ovarian function, and embryo characteristics.

Overview

• This study examined whether the administration of the aromatase inhibitor letrozole affects estrous cycle characteristics, ovarian function, and embryo parameters in non-pregnant mares.
• Researchers found that letrozole treatment during the luteal phase had no significant impact on these reproductive factors in mares.

Background

• Letrozole is a third-generation aromatase inhibitor that blocks the conversion of androgens to estrogens, potentially influencing estrogen-dependent reproductive processes.
• Aromatase inhibitors have been used in various species to manipulate hormone levels and study reproductive function.
• This study sought to clarify the effects of letrozole in horses, particularly regarding estrous cycle behavior and ovarian physiology.

Study Design and Methods

• Subjects: 9 cyclic, non-lactating mares were selected for the study.
• Estrous Synchronization: Mares were synchronized and monitored for ovulation, defined as day 0 (d0) of the treatment cycle.
• Treatments: Mares were randomly assigned in groups of three to either a control group or treatment groups receiving 0.5 mg/kg or 1 mg/kg body weight letrozole orally from day 7 to day 13 of the cycle.
• Post-treatment: Mares were inseminated in the estrus following treatment; ovulation day was recorded (dOv).
• Embryo collection was performed 8 days post-ovulation (dflush) during the post-treatment cycle to assess embryo characteristics.
• Measurements:
• Serum hormone levels – progesterone, estradiol, testosterone, and anti-Mullerian hormone – were measured repeatedly throughout.
• Antral follicle counts (AFC) were performed at multiple timepoints (d0, d4, d7, d13 of treatment cycle and dOv, dflush of post-treatment cycle).

Results

• Estrous cycle characteristics such as length and timing of ovulation were not significantly affected by letrozole treatments compared to controls.
• There were no differences in pregnancy rates or embryo quality parameters between control and letrozole-treated mares.
• Antral follicle counts overall did not differ between treatment groups; however, follicle counts in specific size classes (15 – <20 mm, 20 - <25 mm, 25 - <30 mm, and ≥ 30 mm) varied over time during the study period (statistically significant time effects but not treatment effects).
• Hormone concentrations, including estradiol, progesterone, testosterone, and anti-Mullerian hormone, were not altered by letrozole treatment.

Interpretation and Implications

• The lack of significant changes in estrous cycle length, hormone profiles, and follicular development suggests that letrozole treatment during the luteal phase does not markedly suppress estrogen activity or disrupt normal reproductive physiology in mares.
• This indicates possible species-specific differences in the response to aromatase inhibition or compensatory mechanisms maintaining hormone balance in mares.
• Given the unchanged embryo characteristics and pregnancy rates, letrozole does not appear to impair fertility when administered in the tested doses and timing.
• The study raises questions about the suitability of letrozole for manipulating estradiol function or studying estrogen-dependent reproductive effects in non-pregnant horses.
• Further research may be needed to explore other dosing protocols, administration timings, or alternative approaches for modulating estrogen action in mares.

Conclusion

• Letrozole administration during the luteal phase in cyclic mares does not affect estrous cycle parameters, ovarian function, or embryo characteristics.
• Due to the absence of notable endocrine or reproductive changes, letrozole may not be an effective tool for assessing estradiol function or modulating reproductive physiology in non-pregnant mares under the tested conditions.