Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies.
High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation (IS) that may progress to atrophy. In vivo and in vitro studies addressed possible mechanisms. In vivo, boron tissue disposition was examined, since no detailed data existed, and relevant boron concentrations for in vitro studies needed to be set. Since BA induces riboflavinuria and also affects calcium/phosphorus homeostasis, and testis zinc appears essential for normal testis function, we examined BA effects on flavin status and testis levels of phosphorus (P), calcium (Ca) and zinc (Zn). Data showed that the testicular toxicity and central nervous system (CNS) hormonal effect were not due to selective boron accumulation in testis or brain/hypothalamus, with testis boron concentrations at approximately 1 to 2 mM; that riboflavin deficiency is not involved, due to both the absence of overt signs of deficiency and effects on tissue flavin content during BA exposure; and that changes in testis P, Ca and Zn levels did not precede atrophy, and are therefore unlikely to be mechanistically relevant. In vitro studies addressed the hallmarks of the BA testicular toxicity: the mild hormone effect, the initial IS, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic adenosine monophosphate (cAMP) produces IS, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we examined in vitro BA effects on both Sertoli cell cAMP accumulation and PA activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Chapin
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D000818:Animals; D001284:Atrophy; D001888:Boric Acids / Q000633:toxicity*; D001895:Boron / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000378:metabolism; D014018:Tissue Distribution; D014131:Trace Elements / Q000378:metabolism
D001888:Boric Acids; D014131:Trace Elements; D013739:Testosterone; D000242:Cyclic AMP; D001895:Boron; C032688:boric acid