Inhibition of estrogen synthesis during the last trimester of gestation: changes in endocrine patterns, fetal growth and uterine artery hemodynamics in mares

Abstract

Equine gestation is characterized by very high circulating concentrations of estrogens in the dam. The physiological roles of estrogens during late gestation are largely unknown, although some studies suggest a relationship between low circulating estrogen concentrations and late term pregnancy loss in the mare. Letrozole is a potent aromatase inhibitor that prevents the conversion of androgens to estrogens in the equine placenta. The objective of this study was to evaluate the effect of letrozole on circulating concentrations of estrogens, androgens, and progestins, and on uterine hemodynamics during the last trimester of pregnancy in mares, as well as the effect on fetal development. Multiparous mares of mixed breeds were randomly assigned to control (n1⁄46) or treatment (n1⁄46) groups. Treated mares received 500 mg of letrozole orally every 4 days starting at 240 days of gestation until parturition. Weekly, serum samples were analyzed using enzyme immunoassays to determine estrone sulfate (ES), progestins (P), testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) concentrations. To monitor the status of pregnancy: 1) the mean diameter of the fetal eye was measured as an estimate of fetal growth, 2) uterine artery (UA) diameters and 3) Doppler resistance and pulsatility indices (RI and PI) were determined in both uterine arteries by transrectal Doppler ultrasound every second week. Fetal development was evaluated based on foal weight and