Infertility in a line of mice with the high growth mutation is due to luteal insufficiency resulting from disruption at the hypothalamic-pituitary axis

Animals with extreme body growth frequently experience poor reproductive pe rformance, but the cause for this association has not been clearly establis hed. A line of mice homozygous for the high growth (hg) mutation, a mutatio n that has a major effect on post-weaning growth, exhibits several reproduc tive deficits including an abnormally high incidence of luteal failure. The objective of the present study was to investigate luteal failure in high-g rowth (HG) mice during pregnancy and to determine whether the cause of the apparent luteal failure resides in the ovary or the hypothalamic-pituitary unit. In HG females with a demonstrated history of infertility, progesteron e injections (1 mg s.c. daily) beginning on Day 1 postcoitum (p.c.) increas ed the proportion of animals pregnant at Day 17 of gestation. Twice-daily i njections of 100 mu g of ovine prolactin (PRL) in alkaline saline given to another group of females beginning on Day 1 p.c. increased the proportion o f HC females that were pregnant on Day 6 of gestation compared with saline- injected HC females, although PRL did not increase the pregnancy rate in HG females when compared with a group of noninjected control females. When ov aries from HG females were transplanted into ovariectomized congenic C57 ho sts, the C57 graft hosts displayed normal estrous cycles, and upon mating t he majority of graft hosts became pregnant. In contrast, when ovaries from C57 females were transplanted into ovariectomized HC hosts, the HC graft ho sts displayed normal estrous cycles, but upon mating most were unable to ma intain pregnancy. These results suggest that the hypothalamic-pituitary uni t of the HG female provides an inadequate signal to the ovaries to maintain pregnancy. Luteal failure in HC females may be due to insufficient PRL as required for establishment and early maintenance of the CL during pregnancy in mice.