The dependence of male reproductive toxicity on germ cell stage.
Gandy-J; Teaf-CM; Adatsi-FA; James-RC; Harbison-RD
Functional Teratogenesis: Functional Effects on the Offspring after Parental Drug Exposure. Fujii T, Adams PM, eds., Tokyo, Japan: Teikyo University Press, 1987 Jan; :133-145
A series of experiments were conducted to investigate the dependence of male reproductive toxicity on germ cell stage in rats. Glutathione (GSH) levels were determined in segments of the reproductive tract in sexually mature male Fischer-344-rats with or without treatment with chemicals thought to have reproductive effects. Sexually mature male and female rats were used in a serial mating study of dominant lethal mutations. Clastogenic damage in male germ cell stage dependent dominant lethal mutations results from exposure to ethyl-methanesulfonate (62500) (EMS). The most damage was induced among spermatozoa in late spermatid and early spermatozoal development. Germ cell stage dependent activity of EMS was potentiated by both L-buthionine-sulfoximine (BSO) and 1,2- dibromoethane (106934) (EDB). Both BSO and EDB significantly reduced the epididymal glutathione content, likely the reason for the potentiation effect. At 8 and 16 hours post injection BSO treatment significantly depressed GSH in the epididymis and testes. EDB treatment significantly depressed GSH at 2 hours in caput and cauda epididymis but not in the testes. Trimethyl-phosphate (512561) (TMP) was also able to produce clastogenic damage as well as functionally impair spermatozoa in a dose dependent manner. This impairment was also dependent on germ cell stage. Mature spermatozoa were about four times more susceptible to the actions of TMP, resulting in altered motility. TMP treatment caused a 20 percent reduction in cauda epididymal spermatozoa carnitine- acetyltransferase activity. The authors conclude that overt chemical induced male reproductive toxicity may be dependent on germ cell stage but potency is markedly altered by biochemical influences.
NIOSH-Grant; Reproductive-system-disorders; Laboratory-animals; Alkylating-agents; Cell-function; Toxic-effects; Reproductive-hazards
Pharmacology University of Arkansas 4301 W Markham Little Rock, Ark 72205
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Functional Teratogenesis: Functional Effects on the Offspring after Parental Drug Exposure
University of Arkansas Med Scis Ltl Rock, Little Rock, Arkansas