The Development of Male Reproductive Organ Abnormalities After Neonatal Exposure to Tamoxifen Is Genetically Determined

Abstract

ABSTRACT: Responses of the male reproductive organs to neonatal exposures of tamoxifen (Tx) were examined in seven different strains of mice (A/J, AKR/J, BALB/cAnN, C3H/HeJ, C57BL;6J, DBA/ 2J, and FVB/N). Male mice were given daily subcutaneous injections of 2 μg Tx from postnatal day 1 to 5, and the testes, epididymides, ductus deferens, and seminal vesicles were examined at 3 months of age. At necropsy, the testes and seminal vesicles of Tx‐treated groups 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 testes of A/J, C3H/HeJ, C57BL/6J, and DBA/ 2J mice were often necrotic and highly disorganized, with severe inflammation. In the connective tissue surrounding these testes, relatively large arteries were involved in the inflammation, and the vascular lumen was occluded by the thickened tunica interna, suggesting that these testicular changes were due to infarction. Similarly, the epididymides and ductus deferens of Tx‐treated A/J, C3H/HeJ, C57BL/6J, 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, DBA/2J, and FVB/N mice also exhibited moderate hyperplasia, with squamous metaplasia. These results indicate that neonatal exposure to Tx causes various abnormalities of the male reproductive organs in postpuberal mice, depending on the strains, and suggest that a genetic component plays a major role in determining the phenotypic variation observed.