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Development of Sperm Granulomas in the Epididymides of L-Cysteine-Treated Rats

Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc, Naruto, Tokushima, Japan, sawamoos{at}otsukakj.co.jp, Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka, Japan

Jyoji Yamate

Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka, Japan

Mitsuru Kuwamura

Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka, Japan

Takao Kotani

Laboratory of Veterinary Pathology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka, Japan

Kazunobu Kurisu

Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory, Inc, Naruto, Tokushima, Japan

We investigated the histopathological effects of excess L-cysteine on the male rat reproductive tract during sexual maturation. Male 6-week-old Sprague—Dawley rats were injected intraperitoneally daily with L-cysteine, 1,000 mg/kg body weight, for 1, 2, 3, and 4 weeks. L-Cysteine-treated rats developed sperm granulomas in the epididymides at an incidence of 0% (0/6), 50% (3/6), 83% (5/6), and 100% (6/6) in rats examined at study weeks 1, 2, 3, and 4, respectively. These sperm granulomas were unilateral or bilateral, and most frequently involved the proximal cauda region of the epididymides. Interestingly, small ducts, indicative of immaturity, were seen frequently in L-cysteine-treated rats. These findings suggest that the maturation of epididymides in L-cysteine-treated rats might be delayed. Additionally, dilated ducts and interstitial edema, suggestive of an increase in intraluminal pressure, were seen often in the epididymides of L-cysteine-treated rats. Labeling spermatozoa and epithelial cells with monobromobimane indicated no influence of the thiol—disulfide status of L-cysteine to the epididymides. The testes and prostate glands also showed no effects, suggesting that inhibited epididymis maturation was not a result of hormonal deficiencies. We speculate that defective development of the ducts might result in aberrant fluid flow, leading to ductal rupture in the epididymides. In that case, sperm granulomas might form around leaked spermatozoa.

Key Words: L-Cysteine • sperm granuloma • epididymis • amino acid • apoptosis • rat.

Toxicologic Pathology, Vol. 31, No. 3, 281-289 (2003)
DOI: 10.1080/01926230390204315


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