Antifertility, spermicidal and ultrastructural effects of gossypol and derivatives administered orally and by intratesticular injections.

Because there are problems, in men, associated with the use of gossypol related to reversibility and, infrequently, hypokalemia, several laboratories around the world have resorted to the synthesis and evaluation of experimental analogs and optical isomers of gossypol in an attempt to find a compound which retains its pharmacologically desirable antifertility effects while eliminating its suboptimal ones. The present study documents: (a) the effects of fourteen new, orally-administered synthetic analogs of gossypol on testicular ultrastructure and fertility in hamsters, (b) the in vitro effects of these compounds as well as of the optical isomers of gossypol against hamster and human sperm, and (c) the morphological and antifertility effects of intratesticular injections of gossypol-PVP and its optimal isomers in the rat. The results of the study demonstrate that these new analogs are not effective as male antifertility agents and that their in vitro activity is unrelated to their in vivo contraceptive potential. In addition, this report establishes the validity of the intratesticular injection model for the analysis of the mechanism of action of gossypol and its analogs by making these compounds directly available at the testicular site. The significance of these findings is discussed.