Flutamide induces ultrastructural changes in spermatids and the ectoplasmic specialization between the Sertoli cell and spermatids in mouse testes

Flutamide (Flu) is an anti-androgenic compound that disrupts development of male androgen-dependent tissues. The purpose of the present study was to investigate the effects of Flu on ICR mouse testes by electron microscopic observation. Newborn mice were subcutaneously injected with 0.00012, 0.0012, 0.012, 0.12, 1.2, 12 or 120 mug Flu/g body weight/shot on Days 2, 4, 6, 8, 10 and 12 (Day 1: day of birth). In addition, adult mice were injected with 0.0012, 0.012, 0.12 or 1.2 mug Flu/g body weight/day for 5 sequential days. Testes were processed for electron microscopy. In neonatal treatments, acrosomes and/or nuclei of the spermatids were deformed. In addition, the ectoplasmic specialization between the Sertoli cell and spermatids was partially or completely deleted. Stages of the seminiferous cycle were also disarranged in the neonatal treatments. There were no ultrastructural differences between the effects of neonatal and adult treatments, however, stage disarrangement was not observed in adult treatments. The percentages of abnormal spermatids were higher in neonatally treated mice than in mice treated as adults. Since similar observations were reported after treatment with beta-estradiol-3-benzoate (E2B), the presence of Flu may induce a "xenoestrogenic environment" in mouse testes. (C) 2004 Elsevier Inc. All rights reserved.