Effects of Diabetes on Uterine Condition, Decidualization, Vascularization, and Corpus Luteum Function in the Pseudopregnant Rat

The effects of alloxan-induced diabetes on uterine decidualization and the associated changes in uterine blood flow (UBF) and corpus luteum activity were evaluated in rats between days 4-9 of pseudopregnancy (day 0 = ovulation). Rats were made diabetic (D) with a 40 mg/kg injection (iv) of alloxan on day 1 of pseudopregnancy. Saline-treated rats served as controls (C). Uterine weights were depressed in D rats between days 6-7 of pseudopregnancy in association with elevated blood glucose levels (greater than 300 mg/dl) relative to control values. UBF rates were also depressed in D rats between days 6-7 of pseudopregnancy compared with control values. Insulin replacement therapy (6 IU bovine/day) effectively normalized both uterine weight and UBF in diabetic rats. Decidual tissue (DT) growth was impaired in D rats between days 7 and 9 of pseudopregnancy (DT induction on day 4 of pseudopregnancy) compared with controls. Tissue blood flow rates were severely depressed throughout pseudopregnancy in D rats, but insulin treatment normalized both uterine parameters to control levels. Serum progesterone levels were lower in D rats than in controls between days 7 and 9 of pseudopregnancy. Daily insulin treatment normalized luteal function to control levels. The depressed DT weights in D rats were mimicked by the experimental reduction of DT blood flow in control rats. These results indicate that the uterine atrophy and poor endometrial decidualization that characterized the D rat are accompanied by impaired UBF and luteal activity. These findings suggest that the D-associated depression in female reproductive performance is related to the lack of proper hormone support of tissue vascular dynamics.