Effects of Alloxan-induced Diabetes on Corpus Luteum Function in the Pseudopregnant Rat

The effects of alloxan-induced diabetes mellitus on rat ovarian structure and function were examined throughout pseudopregnancy (PSP). Animals received either saline (C) or alloxan (40 mg/kg) treatment on the day of proestrus (PA) preceding PSP or on day 1 (D-1A) of PSP (day 0 = ovulation). Serum samples were analyzed by radioimmunoassay for progesterone (P) and 17-β-estradiol (E) levels and compared with the corresponding changes in ovarian and uterine weights in C, PA, and D-1A rats. In addition, the effects of daily treatment with 6 IU ovine insulin (Al) on serum P levels were assessed in D-1A-treated rats and compared with controls. Alloxan treatment effectively elevated blood glucose levels (P ≤ 0.01) in PA and D-1 A groups as compared with controls or AI rats. Alloxan treatment reduced both ovarian and uterine weights of PA and D-1A groups as compared with C and Al rats. Serum P levels were significantly reduced in PA (P ≤ 0.01) and D-1 A (P ≤ 0.05–0.01) rats as compared with control rats throughout PSP. Daily insulin treatment reversed the suppressive effects of D-1 A treatment on serum P levels, but did not restore luteal function to control levels. Neither C nor D-1 A groups exhibited any marked differences in serum E levels throughout PSP. The results of these studies indicate that the administration of alloxan before the onset of PSP effectively inhibits luteal function, whereas D-1 A treatment induces early luteolysis as compared with controls. The associated declines in both uterine and ovarian weights reflect the impaired ovarian steroid production associated with diabetes. Since insulin partially restored luteal activity, it is suggested that diabetes-associated reproductive impairment is directly related to an insulin deficiency in the alloxan-treated rat.