EFFECTS OF BOVINE GROWTH-HORMONE (BGH) TRANSGENE EXPRESSION OR BGH TREATMENT ON REPRODUCTIVE FUNCTIONS IN FEMALE MICE

Both physiological and excessive levels of growth hormone (GH) can affect reproductive functions. Overexpression of human (h) or bovine (b) GH in transgenic female mice was previously reported to be associated with reproductive deficits. The objectives of the present study were to determine the age of onset of puberty, the length of the estrous cycle, and the ovulation rate in transgenic and normal mice from a line expressing bGH with the phosphoenolpyruvate carboxykinase (PEPCK) promoter and characterized by very high levels of transgene expression. Transgenic females reached puberty, defined as the appearance of the vaginal introitus, earlier than their normal littermates, but at a higher body weight. Compared to normal animals, an increased number of transgenic females failed to mate during the 15-day period of observation, and pregnancy rates were reduced However, ovulation rates, as estimated by counting CL and implantation sites on Day 7 postcoitum, were increased in transgenic females. Plasma bGH levels in transgenic females ranged from 700 to 2200 ng/ml and were negatively correlated with fertility. To assess the effect of bGH on the ovulation rate in non-transgenic mice, normal females were paired with normal males and injected for up to 3 days with either 0.75 mg bGH/day or 0.30 mg bGH/day (injected as a single dose or as 0.15 mg twice daily). Data from animals that mated after at least 2 days of bGH. treatment were analyzed. The ovulation rate was increased in females treated with 0.75 mg bGH/day, as compared to controls, and in females injected with 0.15 mg bGH twice daily as compared to those given 0.3 mg bGH/day and to controls. Moreover, bGH treatment increased the percentage of animals that failed to mate. We conclude that PEPCK.bGH transgenic females have accelerated sexual maturation and poor reproductive performance as evidenced by reduced mating and pregnancy rates. However, animals that do mate have increased ovulation rates, and females that become pregnant have an increased number of implantations. Comparable changes in fertility can be produced in normal adult mice by injections of bGH.