Rat testis during 2,5-hexanedione intoxication and recovery I. Dose response and the reversibility of germ cell loss.
Toxicol Appl Pharmacol 1988 Jan; 92(1):18-27
In order to evaluate the testicular effects of exposure to 2,5- hexanedione (110134) (2,5-HD) and the reversibility of testicular injury, Charles-River-CD-rats were intoxicated by neurotoxic and subneurotoxic levels of 2,5-HD. One group of rats (low dose group) were injected intraperitoneally with aqueous 2,5-HD at 4 millimoles per kilogram (mmol/kg) per day, 5 days per week for 2 weeks, giving a total dose of 40mmol/kg. Rats were killed 2, 4 or 7 weeks after the beginning of dosing. A second group of rats (moderate dose group) were exposed for 2 or 3 weeks to a 1 percent by volume drinking water solution of 2,5-HD giving average total doses of 90 and 138mmol/kg, respectively. These rats were killed 7 or 22 weeks after the beginning of dosing. A third group of rats (high dose group) were exposed for 5 weeks to a 1 percent by volume water solution of 2,5-HD giving an average total dose of 211mmol/kg. These rats were killed between 2 and 22 weeks after the beginning of dosing. Body weight and clinical neurotoxicity were determined on a weekly basis. Sacrificed rats were examined for testis weight and histopathology, the latter by light microscopy. The low dose group exhibited the longest delay time between intoxication and development of testicular injury. In these animals Sertoli cell vacuolation was observed at 4 weeks with focal loss of germ cells at 7 weeks. Moderate exposure levels resulted in seminiferous tubule depopulation followed by variable germ cell repopulation. Following a 17 week recovery period, three of five rats in the high dose group had only stem cell spermatogonia and Sertoli cells within their seminiferous tubules. The author concludes that 2,5-HD intoxication at both subneurotoxic and neurotoxic levels results in an extended period of germ cell depopulation.
NIOSH-Publication; NIOSH-Grant; Reproductive-system-disorders; Laboratory-animals; In-vivo-studies; Ketones; Testes; Spermatozoa; Pathomorphology; Neurotoxins; Histomorphology
Pathology and Lab Medicine Div. of Biology and Medicine Brown University, Box G Providence, RI 02912
Toxicology and Applied Pharmacology
Brown University, Providence, Rhode Island