A biochemical basis for 1,2-dibromo-3-chloropropane-induced male infertility: inhibition of sperm mitochondrial electron transport activity.
A rapid decrease in male fertility in laboratory animals exposed to 1,2-dibromo-3-chloropropane (DBCP) has been suggested to be due, in part, to a postglycolytic inhibition of sperm carbohydrate metabolism. The present studies were performed to identify the specific site of DBCP-induced inhibition of intermediary metabolism. 14CO2 generation by epididymal sperm, isolated from Fischer 344 rats, was measured using radiolabeled tricarboxylic acid (TCA) cycle intermediates: acetyl CoA, citrate, alpha-ketoglutarate, and succinate. There was 0-28% inhibition of CO2 generation after addition of 0.5 mM DBCP and 81-98% inhibition with 3 mM DBCP, with all four substrates. The activities of alpha-ketoglutarate dehydrogenase, pyruvate dehydrogenase, malate dehydrogenase, and lactate dehydrogenase were not inhibited by DBCP. Since the DBCP-induced inhibition of metabolism of different substrates to CO2 was similar, and since DBCP did not inhibit enzyme activities of glycolysis or the TCA cycle, a common site of inhibition was suspected. In evaluations of mitochondrial electron transport chain activity, DBCP (3 mM) inhibited oxygen consumption resulting from metabolism of endogenous substrates plus alpha-ketoglutarate or malate by about 80%. When succinate, an FAD-dependent oxidation, was used as a substrate, oxygen consumption was not inhibited by DBCP. It is concluded that DBCP inhibits sperm carbohydrate metabolism at the NADH dehydrogenase step in the mitochondrial electron transport chain.
Greenwell
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A
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Tomaszewski
K E
KE
Melnick
R L
RL
D000818:Animals; D004579:Electron Transport; D066298:In Vitro Techniques; D007248:Infertility, Male / Q000139:chemically induced*; D007306:Insecticides / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*
D007306:Insecticides; C007318:1,2-dibromo-3-chloropropane; D010088:Oxidoreductases; D011407:Propane