TAMOXIFEN-INDUCED LIGHT AND ELECTRON-MICROSCOPIC CHANGES IN THE RAT TESTICULAR MORPHOLOGY AND SERUM HORMONAL PROFILE OF REPRODUCTIVE HORMONES

The effects of oral administration of tamoxifen at doses of 40 and 200 mu g/kg/day on testicular histology, testicular ultrastructure and se rum hormonal profile were studied. The drug was administered to adult male mts over a period of 90 days and the effect was assessed at 10-da y intervals. The morphometry, microscopic structures of the testis, in cluding ultrastructure and daily sperm production rate, were evaluated . The hormone profiles of luteinizing hormone (LH), follice-stimulatin g hormone (FSH), testosterone, and estradiol were studied. The testes from treated animals showed disorganization of tubular elements with i ncreased intercellular space. At day 50, the changes were extensive in cluding presence of phagosomes. Morphometric studies showed a reductio n in the spermatid and spermatozoan population (69.3%) with no changes in tubular diameter. The mean Leydig cell area was significantly lowe red at day 50, at both doses. The daily sperm production rate was redu ced as compared with controls. An array of degenerative changes were r evealed by ultrastructural studies. The changes were extensive at day 50 at both doses. The characteristic features were lost in most of the cells with phagolysosomes becoming abundant. The cytoplasm of the cel ls was dense with poorly defined cytoplasmic organelles. Circulating L H levels were not modified at the 40 mu g/kg/day dose but at 200 mu g/ kg/day, LH levels were significantly decreased. Initial transitory ris e in FSH was seen with both doses. Both doses of tamoxifen decreased t estosterone levels. Changes in the circulating estradiol levels were i nconsistent, and no apparent relationship between dose and days of tre atment was observed. Thus, this study supports our thesis of tamoxifen as a potential male contraceptive agent. CONTRACEPTION 1998;57:261-26 9 (C) 1998 Elsevier Science Inc. All rights reserved.