5-Fluorouracil (5-FU) has been widely used clinically in the treatment for malignancies. Even though it has long been proved to be a gonadotoxic and mutagenic agent, its effect on sperm morphology has not been well documented in the literature. In our study, 60 male adult albino rats (170 g ~ 200 g) were divided into 4 groups: a control group and 3 treated groups receiving 10 mg·kg^-1·day^-1, 20 mg·kg^-1·day^-1 and 30 mg·kg^-1·day^-1 of 5-FU, i.p., respectively, for five days. Each group was then divided into three sub-groups of five rats each for obtaining sperm samples at 35 days, 42 days or 70 days post exposure. Epididymal sperm smears were then prepared, stained with eosin-Y and examined under a microscope to differentiate the sperm morphology. Data were analyzed by Mann Whitney U test. Results indicated a dose-dependent increase (P<0.01) in the number of abnormal spermatozoa with the highest rate of abnormality on day 42. The different types of abnormalities included amorphous, coiled, double headed, double tailed and double headed/double tailed spermatozoa. We previously confirmed the toxic effects of 5-FU on the testis, causing germinal cell sloughing, tubular atrophy and a decline in sperm concentration [1-4]. An increase in the number of abnormal spermatozoa had the potential to adversely affect male fertility. This teratozoospermic effect may be genotoxic, as 5-FU is a potent DNA alkylating agent. The decreased level of testosterone on exposure to 5-FU, as reported earlier by Takizawa and Horii [5], supported the present finding of sperm abnormality. The present study confirmed that 5-FU adversely affected the morphology of spermatozoa, resulting in both head and tail anomalies.

References

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[2] D'Souza UJA, Narayana K. Induction of seminiferous tubular atrophy by single dose of 5-fluorouracil in Wistar rats. Indian J Physiol Pharmacol 2001; 45: 87-94.
[3] D'Souza UJA, Narayana K. Formation, morphology and fate of multinucleated cells (symplasts) in the rat testis exposed to 5-fluorouracil. Indian J Physiol Pharmacol 2002; 46: 504-6.
[4] D'Souza UJA. Toxic effects of 5-fluorouracil on sperm count in Wistar rats. Malaysian J Med Sci 2003; 1: 43-5.
[5] Takizawa LD, Horii I. Endocrinological assessment of toxic effects on the male reproductive system in rats treated with 5-fluorouracil for 2 or 4 weeks. J Toxicol Sci 2002; 27: 49-56.