THE EFFECTS OF BORIC-ACID (BA) ON TESTICULAR CELLS IN CULTURE

High-dose boric acid (BA) exposure produces testicular lesions in adul t rats characterized by inhibited spermiation that may progress to non recoverable atrophy. The mechanism for the testicular toxicity of BA i s unknown. To examine possible direct effects, the present study evalu ated selected aspects of various testicular cell culture systems after in vitro BA exposure. Specifically, the hallmarks of the BA testicula r toxicity were addressed: the mild hormone effect, the initial inhibi tion of spermiation, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the conten tion of a CNS-mediated rather than a direct hormone effect. Since incr eased testicular cyclic AMP (cAMP) produces inhibited spermiation, and a role for the serine proteases plasminogen activators (PAs) in sperm iation has been proposed, we evaluated both Sertoli cell cAMP accumula tion in Sertoli-germ cell cocultures and the stage-specific secretion of PA activity in cultured seminiferous tubules after in vitro BA expo sure, 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 t) 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, b ecause germ cells synthesize DNA/RNA and BA impairs nucleic acid synth esis in liver and may do so in testis. Despite the absence of overt mo rphologic changes and germ cell loss, the most sensitive in vitro endp oint was DNA synthesis of mitotic/meiotic germ cells, with energy meta bolism in Sertoli or germ cells affected to a lesser extent. A re-eval uation of testis sections from rats exposed to BA revealed a decrease in the early germ cell/Sertoli cell ratio prior to atrophy. Thus, alth ough the mechanism for the inhibited spermiation is still undefined an d 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.