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Abstract for RACB88120

Reproductive Toxicity of Dietary Restriction in CD-1 Swiss Mice

Report Date: July 1990


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

Weight loss is a common indicator of toxicity. It can be a confounding factor in routine toxicological studies, as the endpoints being evaluated may be affected by reduced body weight. While many studies have evaluated the effect of diet restriction on the development of reproductive function, few studies have reported the effect(s) of restricted diet on adults. This particular study was conducted to determine how weight loss affects male and female reproduction in Swiss CD- 1 mice. Control animals received NIH-07 pelleted feed (19 pellets especially milled for our study) ad libitum. Restriction levels were set at 90%, 80%, and 70% of the mean control body weight. To obtain these target weights and maintain them, experimental animals were fed once in the morning; the ration was adjusted based on the twice-weekly body weights.

Estrual cyclicity was evaluated during the last week of quarantine, and study weeks 6-7 and 14-15. After the last vaginal smearing during week 15, each female was mated with an ad lib male until detection of a vaginal plug, or for a maximum of 7 days. On gestation day 14, females were necropsied. Feed-restricted males, during weeks 8 and 15, were each mated with 2 females. Litters were evaluated at delivery. Reproductive organ weights were collected, along with data on epididymal sperm density, motility, and morphology. Histopathological examination was conducted on selected tissues and organs.

The mean number of litters per male was significantly reduced in all restricted groups in mating trial I. In mating trial II, the number of live male pups and total live pups per litter also declined and the response was "dose"-related. In the females, an increase in the proportion of fertile animals with resorptions, and decrease in number of live fetuses/implants was observed at week 16. Vaginal cytology studies showed that in the 70% cbw group, the estrous cycle length was extended and a significant number of animals were not cycling. Sperm assessment studies showed adverse effects on sperm count, testicular spermatid head count, and incidence of abnormal sperm.