Studies on the antitesticular action of DL-6-(N-2-pipecolinomethyl)-5-hydroxy-indane (PMHI) in the rat.

ABSTRACT

Both prepubertal and adult rats were treated with a single oral dose of either 60 mg or 120 mg of dl-6-(N-pipecolinomethyl)-5-hydroxy indane maleate (PMHI) per kg of body weight. Their testicular weights were drastically reduced compared with those of the controls. A follow-up, beginning on the third day post-treatment and continuing for a period of 50 days, showed that the body weight growth of PMHI-treated rats was not retarded. The hormonal profile indicated that, except for FSH which showed a transitory elevation in PMHI-treated immature rats, the serum levels of LH, estrogen, and testosterone were indistinguishable from those of the controls. Testicular histology revealed that the spermatogenic process in PMHI-treated rats recovered at a dose-related rate. EM sections of testes of adult rats indicated that cytoplasmic vacuolation appeared in the Sertoli cells 5 h post-treatment. The consequent cascade of arrested spermiogenesis included abnormal acrosomal condensation of spermatids and sloughing of polynucleated spermatids. Some spermatocytes also seemed to be affected, but spermatogonia and Leydig cells remained intact. These results indicate the PMHI acts primarily on Sertoli cells and causes arrest in the spermiogenetic stage of the spermatids. At a higher and toxic dose of PMHI, however, the earlier germinal elements might also be affected, due to the extensive damage to the supporting Sertoli cells.