Mice that are homozygous for the autosomal recessive mutation diabetes (db) fail to reproduce. We have established that the hypoplastic vaginal epithelia, uteri and ovaries can respond comparably to control tissues on hormonal stimulation. Gonadotropin release from the pituitary gland appeared to be depressed in female mutant mice, but responded normally to exogenous gonadotropin releasing hormone (GNRH) in both sexes. Immature mutant females failed to ovulate on PMS stimulation. Hypothalamic GNRH content was greater than normal in the adult female mutant mice (<0.001), suggesting that in the females, at least, GNRH release may be inadequate, with secondary blunting of pituitary function.

The db males appeared to have comparable to normal LH, FSH and GNRH levels and little sign of reproductive tract atrophy. Only the preputial glands were significantly reduced from normal size. The db males did fail to show mating behavior. The results substantiate a hypothesis that the presumed single gene mutation, diabetes, acts through a CNS anomaly to cause infertility, as it also may act to cause obesity and thermoregulatory disturbances.

Author notes

Supported by NIH grant NSI 1237.