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Updated: Aug 19, 2026

Determination of Reproductive Competence by Confirming Pubertal Onset and Performing a Fertility Assay in Mice and Rats
Published on: October 13, 2018
The effects of feed restriction on reproductive function in Swiss CD-1 mice
R E Chapin1, D K Gulati, P A Fail
1Developmental and Reproductive Toxicology Group, NIEHS, National Toxicology Program, Research Triangle Park, North Carolina 27709.
Abstract:
Many test compounds used in toxicity studies produce a "systemic" toxicity manifested as reduced body weight gain. While it is known that reduced weight gain during juvenile growth reduces or delays reproductive competence, the effects of adult-onset feed restriction (FR) and inhibited weight gain on the reproductive system of mice are poorly known. To gain some information on the effects of graded body weight reduction, or reduced body weight gain, on commonly used reproductive endpoints, the studies reported below were conducted at two laboratories, using adult mice that were maintained at 90, 80, and 70% of concurrent control body weight (CBW) for up to 21 weeks. Estrous cyclicity and fertility in the females were significantly affected. While male fertility was variably affected, there was a significant decrease in the number of epididymal sperm and in the number of testicular spermatids in the 70% CBW groups. Testis weight was conserved in both studies; relative testis weight increased in all FR groups. These data can improve the interpretation of future studies by helping to separate chemically induced changes from those produced by reduced body weight gain.
Insights
Adult feed restriction significantly impacts mouse reproductive health, affecting female estrous cycles and fertility. Male mice showed reduced sperm counts, highlighting the need to distinguish weight gain effects from chemical toxicity.
Area of Science:
- Toxicology
- Reproductive Biology
- Animal Models
Background:
- Systemic toxicity in toxicity studies often presents as reduced body weight gain.
- The impact of adult-onset feed restriction (FR) on reproductive systems is not well understood.
- Juvenile weight gain reduction is known to affect reproductive competence.
Purpose of the Study:
- To investigate the effects of graded body weight reduction on reproductive endpoints in adult mice.
- To differentiate chemically induced toxicity from effects of reduced body weight gain.
Main Methods:
- Adult mice were maintained at 90%, 80%, and 70% of concurrent control body weight (CBW).
- Studies were conducted over a period of up to 21 weeks at two laboratories.
- Evaluated reproductive endpoints included estrous cyclicity, fertility, sperm counts, and testis weight.
Main Results:
- Female estrous cyclicity and fertility were significantly affected by feed restriction.
- Male fertility was variably affected, with significant decreases in epididymal sperm and testicular spermatids at 70% CBW.
- Testis weight was conserved, but relative testis weight increased in all FR groups.
Conclusions:
- Adult-onset feed restriction negatively impacts reproductive endpoints in mice.
- These findings aid in distinguishing weight-gain-related effects from chemical toxicity in toxicological studies.
- Understanding these effects is crucial for accurate interpretation of toxicity study outcomes.

