Leuprolide acetate improves ovarian indices but does not restore uterine morphometry in obese Zucker rats

Obesity is associated with disrupted estrous cyclicity, impaired follicular development, and altered uterine responses. Leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, produces time-dependent effects on the reproductive axis; however, its actions under severe obesity remain poorly defined. This study evaluated the effects of LA on metabolic parameters, estrous cyclicity, ovarian morphology, and uterine morphometry in obese Zucker rats. Thirty-six adult female rats were used: normal-weight Long-Evans (LE) and obese Zucker (OZ) rats were assigned to untreated control, vehicle, or LA-treated groups (n = 6/group). LA was administered subcutaneously at 2.5 μg/rat/day for 21 consecutive days. Estrous cyclicity was evaluated before and during treatment, and metabolic, ovarian, and uterine outcomes were assessed after treatment. Obese Zucker rats exhibited greater adiposity, metabolic alterations, prolonged and disrupted estrous cycles, impaired follicular development, increased follicular atresia, fewer corpora lutea, and altered uterine morphometry. LA produced condition-dependent reproductive responses. In obese rats, LA shortened the prolonged estrous cycle and shifted estrous-stage distribution toward the pattern observed in normal-weight animals. LA also increased healthy, developing, antral, and preovulatory follicles, markedly increased corpora lutea, and reduced follicular atresia and cystic structures. In contrast, LA produced predominantly suppressive follicular and estrous-cycle changes in normal-weight rats. LA markedly reduced total cholesterol in obese rats without modifying serum glucose, whereas no condition-specific treatment effect on triglycerides was detected. At the uterine level, LA reduced uterine diameter in obese rats but did not modify endometrial thickness. These findings indicate that LA produces markedly different reproductive responses according to the metabolic and reproductive context, improving several follicular and luteal histomorphometric indices in obese Zucker rats without a parallel restoration of uterine morphometry.