The genetically obese Zucker rat is characterized by multiple metabolic and endocrine abnormalities including reproductive dysfunction. Obese males copulated but less vigorously and less frequently than lean males. Obese females reported to be uniformly sterile, have severely limited reproductive capacity. However, some aspects of reproductive function were found to be less abnormal than previously reported. Pseudopregnancy and the decidual response can be induced in obese females. Obese females also become pregnant following artificial inemination, but pregnancies consistently fail at mid-term with embryo resorption occurring between days 8-14. In pseudopregnant- decidualized rats, regression of decidual tissue occurs prematurely, also between days 8-14. These two phenomena suggest a deficiency of progesterone during this period. Considering that LH is the major luteotrophic hormone during days 8-11 of pregnancy and pseudopregnancy, a deficiency in LH is proposed to explain the apparent inadequate progesterone secretion. This hypothesis will be tested by artificially inseminating obese rats and treating them with hCG, days 8-11 of pregnancy. Pseudopregnant decidualized rats will be similarly treated. An additional group of rats will be food-restricted by pair feeding to lean controls and the effects of food restriction on pregnancy rate and maintenance investigated. Serum progesterone and LH concentrations for days 8-14 of pregnancy and pseudopregnancy will be determined by RIA; some rats will be sacrificed on day 8 and the rest on day 14. Uteri and ovaries, will be examined histologically for functional differences. The data gathered from these experiments is expected to help elucidate the mechanism(s) of reproductive dysfunction in the obese rat, specifically those causing pregnancy failure. Finally, the information will serve as a basis for developing a method of maintaining pregnancy to term. If litters can be produced by matings of homozygous (fa/fa) obese pairs, all of the offspring will be destined to become obese. Matings of heterozygous (Fa/fa) pairs result in only 25% obese offspring, and these offspring are not visibly identifiable before 3-4 weeks of age. The production of entire litters of obese animals will offer a compelling advantage to the study of early factors, even prenatal factors, involved in the etiology of obesity and diabetes, two diseases for which the genetically obese Zucker rat is an animal model.
