Abstract for RACB89041

Reproductive Toxicity Associated with Feed Restriction in Sprague-Dawley Rats

Report Date: Oct. 29, 1991


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.

Most chemical toxicity studies involve treating adult animals with doses sufficient to depress body weight gain to varying degrees. Large reductions in body weight gain in juveniles are associated with impaired reproductive function, but little is known about the reproductive effects on adults. For this reason, the effects of adult-onset body weight restriction on male and female reproduction in CD Sprague- Dawley rats were tested. Male and female rats were singly housed and allowed ad libitum access to water. Control animals received NIH-07 pelleted feed 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 twice-weekly body weights. In the control and restricted females, estrual cyclicity was evaluated during the last week of quarantine and study weeks 8-9 and 14-15. After the last vaginal smearing, each female was mated with an ad lib-fed male, until detection of a vaginal plug, or for a maximum of 7 days. On gestation day 14, females were necropsied and uterine contents and organ weights were assessed. Control and restricted males, subject to two mating trials, were mated with two females each during weeks 8 and 15. Litters were evaluated at delivery. At terminal necropsy, reproductive organ weights were collected, along with data on epididymal sperm density, motility, and morphology and testicular spermatid head count. The number of corpora lutea per animal decreased significantly in the 70% cbw group. Absolute liver weight significantly decreased in the 70% cbw females and the right ovary- and kidneys-to-body weight ratios significantly increased in the 70 and 80% cbw groups compared to the control group.

In males, food restriction at up to 70% cbw level had no adverse effect on litter parameters in both mating trials. In fact, the average number of litters per male was either equal to or higher than the control values. At terminal male necropsy, absolute weights for a number of organs were significantly decreased and organ-to-body weight ratios were significantly increased.

Overall, it is concluded that under the present experimental design, food restriction had minimal effects on reproductive endpoints and fertility in Sprague-Dawley rats.