Examination of the ovotoxicity of 5-fluorouracil in mice

M. Lambouras, S. H. Liew, K. Horvay, H. E. Abud, J. M. Stringer, Karla J. Hutt

Undesirable side effects of cancer treatments are common and include damage to the ovary, and depletion of the follicle reserve, which if severe enough, can lead to infertility and early menopause. Antimetabolite drugs, such as 5-fluorouracil (5-FU), are not considered to be detrimental to the ovary, but the ovotoxicity of 5-FU has not been evaluated in any detail. The purpose of this study was to evaluate the effects of 5-FU on follicle number. In this study, adult female C57Bl6 mice (n = 4-6 animals/group) received a single dose of saline or 5-FU (150 mg/kg) and markers of ovarian damage and follicle depletion were assessed 12 h and 7 days later. Exposure to 5-FU did not alter primordial and primary follicle numbers. Atresia of secondary and antral follicles was increased significantly 12 h after 5-FU treatment, but atresia rates returned to levels similar to that of saline treated controls at 7 days. The number of corpora lutea were reduced 7 days after exposure to 5-FU, possibly as a consequence of earlier follicular atresia. These findings suggest that a single dose of 5-FU is mildly ovotoxic, but any effects on ovarian function are likely transient because the primordial follicle population is not depleted. Collectively, these data support the notion that 5-FU is unlikely to impact on the long-term fertility of women.