Abstract
In recent years, 6-MP treatment has been beneficial in the treatment of inflammatory bowel disease (IBD). Since 6-MP and its metabolites interfere with various steps in nucleic acid biosynthesis, chronic use of 6-MP could theoretically alter normal cell turnover, including spermatogenesis. Therefore, we have investigated the effect of daily 6-MP administration on spermatogenesis in the young rat. 6-Mercaptopurine was administered in clinically relevant doses 24 and 40 mg/m2. Testicular weights of rats treated with 24 mg/m2 for 75 days or 40 mg/m2 for 25 days were not significantly different among 6-MP, pair-fed, orad libitum chow-fed groups. Quantitation of the stages of seminiferous tubules or the number of homogenization-resistant, mature spermatids per testis were not affected by 6-MP treatment. In addition, 6-MP had no effect on serum testosterone or on HCG-stimulated testosterone release by the testes. These results suggest that chronic low-dose 6-MP therapy, as used in the treatment of IBD, may not carry as great a risk for suppression of spermatogenesis as theorized. Our study in animals indicates that evaluation of 6-MP and spermatogenesis in man is warranted.
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References
Korelitz BI, Present DH: Favorable effect of 6-mercaptopurine on fistulae of Crohn's disease. Dig Dis Sci 30:58–64, 1985
Elion GB: Biochemistry and pharmacology of purine analogs. Fed Proc 26:898–904, 1967
Elion GB: Historical background of 6-mercaptopurine. Toxicol Ind Health 2:1–9, 1986
Reimers TJ, Sluss PM, Goodwin J, Seidel GE Jr: Bigenerational effects of 6-mercaptopurine on reproduction in mice. Biol Reprod 22:367–375, 1980
Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE: Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man. Cancer Chemother Rep 50:219–244, 1966
Parvinen M:Regulation of the seminiferous epithelium. Endocrine Rev 3:404–415, 1982
Perey B, Clermont Y, Leblond CP: The wave of the seminiferous epithelium in the rat. Am J Anat 108:47–77, 1961
Robb GW, Amann RP, Killian GJ: Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J Reprod Fertil 54:103–107, 1978
Clermont Y: Kinetics of spermatogenesis in mammals: Seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev 52:198–236, 1972
Payne AH, Kelch RP, Murano EP, Kerlan JT: Hypothalamic, pituitary and testicular function during sexual maturation of the male rat. J Endocrinol 72:17–26, 1976
Glass AR, Mellitt R, Vigersky RA, Swerdloff RS: Hypoandrogenism and abnormal regulation of gonadotropin secretion in rats fed a low protein diet. Endocrinology 104:438–442, 1979
Oakberg EF, Crosthwait CD, Raymer GD: Spermatogenic stage sensitivity to 6-mercaptopurine in the mouse. Mutat Res 94:165–178, 1982
Cosentino MJ, Chey WY, Takihara H, Cockett ATK: The effects of sulfasalazine on human male fertility potential and seminal prostaglandins. J Urol 132:682–686, 1984
Penso J, Lippe B, Ehrlich R, Smith FG Jr: Testicular function in prepubertal and pubertal male patients treated with cyclophosphamide for nephrotic syndrome. J Pediatr 84:831–836, 1974
Qureshim SA, Pennington JH, Goldsmith HJ, Cox PE: Cyclophosphamide therapy and sterility. Lancet 2:1290–1291, 1972
Guesry P, Lenoir G, Broyer M: Gonadal effects of chlorambucil given to prepubertal boys for nephrotic syndrome. J Pediatr 92:299–303, 1978
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This project was funded by a grant from Reach Out for Youth with IBD.
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Karl, P.I., Katz, R., Daum, F. et al. 6-mercaptopurine and spermatogenesis in the young rat. Digest Dis Sci 36, 1569–1573 (1991). https://doi.org/10.1007/BF01296399
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DOI: https://doi.org/10.1007/BF01296399