The development of male reproductive organ abnormalitites after neonatal exposure to tamoxifen is genetically determined

Responses of the male reproductive organs to neonatal exposures of tamoxife n (Tx) were examined in seven different strains of mice (A/J, AKR/J, BALB/c AnN, C3H/HeJ, C57BL/6J, DBA/ 2J, and FVB/N). Male mice were given daily sub cutaneous injections of 2 mu g Tx from postnatal day 1 to 5, and the testes , epididymides, ductus deferens. and seminal Vesicles were examined at 3 mo nths of age. At necropsy, the testes and seminal vesicles of Tx-treated gro ups were significantly smaller in size than those of the control groups in all strains. Histologically, the testes of AKR/J, BALB/cAnN, and FVB/N mice showed no abnormality after neonatal treatment with Tx. In contrast, the t estes of A/J, C3H/HeJ, C57BL/6J, and DBA/ 2J mice were often necrotic and h ighly disorganized, with severe inflammation. In the connective tissue surr ounding these testes, relatively large arteries were involved in the inflam mation, and the vascular lumen was occluded by the thickened tunica interna , suggesting that these testicular changes were due to infarction. Similarl y, the epididymides and ductus deferens of Tx-treated A/J, C3H/HeJ, C57BL/6 J, DBA/2J, and FVB/N mice showed chronic pyogranulomatous inflammation. The epithelium of the seminal vesicles of Tx-treated A/J, C3H/HeJ, C57BL/6J, D BA/2J, and FVB/N mice also exhibited moderate hyperplasia, with squamous me taplasia. These results indicate that neonatal exposure to Tx causes variou s abnormalities of the male reproductive organs in postpubertal mice, depen ding on the strains, and suggest that a genetic component plays a major rol e in determining the phenotypic variation observed.