Male reproductive toxicity of 6-aminonicotinamide
Abstract
Studies were conducted to characterize the effects of 6-aminonicotinamide on prenatal and postnatal testicular development and on the testis and fertility of male Sprague-Dawley rats. Clinical signs were similar in all 6-AN treated rats, varied in severity and included progressive hindlimb weakness, oculo-nasal discharge, rough pilage and weight loss. Subcutaneous administration of 6.0 mg of 6-AN/kg of body weight to pregnant female rats resulted in reductions in the number of gonocytes in the testes of fetal rats. Microscopic alterations in testes of neonatal rats given 3.0, 6.0 or 12.0 mg of 6-AN/kg of body weight included significant dose dependent reductions in the numbers of spermatogonia and supporting cells. Other alterations included, cytoplasmic vacuolation of the basal layers of the squamous mucosa of the stomach of treated female and neonatal rats and ulceration of the glandular gastric mucosa in female rats. In adult male rats, single injections of 12.0 or multiple injections of 3.0 and 6.0 mg of 6-AN/kg of body weight produced microscopic alterations in approximately 30% of the seminiferous tubules/testicular cross-section. In these animals, the principal microscopic and ultrastructural lesion was degeneration and necrosis of syncytia of primary spermatocytes in the pachytene phase of meiosis. The morphologic pattern of cell death was consistent with apoptosis and included condensation and contraction of the cytoplasmic matrix and nuclear chromatin, blebbing of cytoplasmic membranes, fragmentation of affected cells and phagocytosis of cell fragments by Sertoli cells. Alterations were first observed ultrastructurally 24 hrs post injection. Pachytene spermatocytes in the VIIth and VIIIth stages of the cycle of the seminiferous epithelium were preferentially affected. 6-Aminonicotinamide failed to reduce the number of sperm produced per gram of testis and affect fertility when administered biweekly at doses of 1.0, 3.0 and 5.0 mg of 6-AN/kg of body weight to adult male rats.
Degree
Ph.D.
Advisors
Carlton, Purdue University.
Subject Area
Veterinary services
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.