A novel action of insulin sensitizing drug as a potential promotor of preovulatory follicles, ovulation rate and prolificacy in sheep.

Abstract

The effect of the insulin-sensitizing drug metformin on preovulatory follicle (POF) number, ovulation rate, fetal rate and prolificacy was studied in forty-six cyclic Malpura ewes. After estrus synchronization, the ewes were equally divided into two groups (n = 23). The treatment group (MET) received a daily oral dose of metformin at a rate of 500mg/animal for approximately 12 weeks, spanning five estrous cycles, as against untreated control (CON). All the ewes were bred to proven rams at the end of treatment. Ovarian ultrasound scans were performed at each estrus and day 9 of each cycle to assess the number and diameter of POFs and corpora lutea (CL), respectively. A comprehensive assessment of circulating hormones including, estradiol, progesterone, androstenedione, and insulin as well as metabolic indicators such as glucose, and lipid profile parameters was performed. At the end of treatment on the day of estrus (E5D0), the treatment showed a stimulatory effect on follicular development with a 53.2% (P < 0.001) increase in the number of POFs. It also increased the ovulation rate by 67.4% (P < 0.01), with a higher proportion (χ2df1 = 10.7, P < 0.001) of ewes in the MET group having multiple ovulations compared to the CON group (82.6 vs. 30.4%). With 1.48 ± 0.12 prolificacy rate in MET ewes, the proportion of ewes giving birth to multiple lambs was 2.9-fold higher than in the CON group. Plasma estradiol, insulin, glucose, total cholesterol, and LDL-cholesterol concentrations were lower (P < 0.05) in the MET ewes than in the CON. The results of the present study indicate that metformin can increase the number of POF, ovulation rate, fetal rate and prolificacy in ewes, while reducing the plasma estradiol, insulin, glucose and cholesterol in MET ewes.