The effects of boric acid (BA) on testicular cells in culture.
High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation that may progress to nonrecoverable atrophy. The mechanism for the testicular toxicity of BA is unknown. To examine possible direct effects, the present study evaluated selected aspects of various testicular cell culture systems after in vitro BA exposure. Specifically, the hallmarks of the BA testicular toxicity were addressed: the mild hormone effect, the initial inhibition of spermiation, 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 AMP (cAMP) produces inhibited spermiation, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we evaluated both Sertoli cell cAMP accumulation in Sertoli-germ cell cocultures and the stage-specific secretion of PA activity in cultured seminiferous tubules after in vitro BA exposure, respectively. The results showed that the inhibited spermiation is not due to BA effects on either process. To address the atrophy, we evaluated BA effects in Sertoli-germ cell cocultures on 1) morphology/germ cell attachment, which might identify a target cell; 2) Sertoli cell energy metabolism, because lactate, secreted by Sertoli cells, is a preferred energy source for germ cells; and 3) DNA/RNA synthesis, because germ cells synthesize DNA/RNA and BA impairs nucleic acid synthesis in liver and may do so in testis. Despite the absence of overt morphologic changes and germ cell loss, the most sensitive in vitro endpoint was DNA synthesis of mitotic/meiotic germ cells, with energy metabolism in Sertoli or germ cells affected to a lesser extent. A re-evaluation of testis sections from rats exposed to BA revealed a decrease in the early germ cell/Sertoli cell ratio prior to atrophy. Thus, although the mechanism for the inhibited spermiation is still undefined and is the subject of future work, these combined studies revealed some changes offering a plausible explanation for the atrophy aspect of the BA testicular lesion.
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Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Shih
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Chapin
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D000818:Animals; D001888:Boric Acids / Q000633:toxicity*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010960:Plasminogen Activators / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis
D001888:Boric Acids; D013739:Testosterone; D012313:RNA; D005640:Follicle Stimulating Hormone; D004247:DNA; D000242:Cyclic AMP; D010960:Plasminogen Activators; D001973:Bromodeoxyuridine; C032688:boric acid