Studies on the Male Antifertility Agent - Gossypol Acetic Acid. III. Effect of Gossypol Acetic Acid on Rat Testis

Abstract

Summary Gossypol acetic acid at the dose of 5 mg/rat/day for 2 and 4 weeks did not cause any significant effect on the body weight, testis, epididymis, seminal vesicle and prostate weight, nor gossypol treatment had any significant effect on the activities of acid phosphatase and succinic dehydrogenase in the testis. Changes in the testis ATPase activity were, however, significant after gossypol treatment. During the course of present investigations no effect of gossypol treatment on 3H thymidine incorporation into DNA of testicular cells was observed, nor there were any changes in the DNA and total protein content of the testis after gossypol treatment. Gossypol treatment did not cause any effect on the plasma Na+ level. However, transient decrease in the plasma K+ level was observed; decrease in K+ level two weeks after gossypol treatment was restored to normal after 4 weeks of gossypol treatment. No changes in the histology of the testis were observed 2 weeks after gossypol treatment but marked inhibition of spermatogenesis was observed 4 weeks after gossypol treatment. Motility of vas deferens spermatozoa was also markedly inhibited 4 weeks after gossypol treatment. In the light of the present observations and those of others, there is a clear demonstration that gossypol acts directly on the spermatozoa and on the testis; at both the sites the drug interferes in the ATPase activity. Untersuchungen über die Antifertilitätssubstanz Gossypol‐Essigsäure. III. Der Einfluß von Gossypol‐Essigsäure auf den Rattenhoden Zusammenfassung Gossypol‐Essigsäure (G) ‐ in einer Dosis von 5 mg/Ratte/Tag für 2 und 4 Wochen appliziert ‐ verursacht keine signifikanten Veränderungen des Körpergewichtes, des Gewichtes der Hoden, Nebenhoden, Samenblasen und Prostata; G‐Behandlung hat auch keinen Einfluß auf die Aktivität der sauren Phosphatase und der Succinatdehydrogenase des Hodens. Demgegenüber konnte eine Änderung der ATPase‐Aktivität nach G. festgestellt werden. Im Verlauf der gegenwärtigen Untersuchungen ließ sich kein Einfluß von G auf den 3H‐Thymidin‐Einbau in DNA von Hodenzellen beobachten. Auch ergaben sich keine Veränderungen des Gehaltes an DNA und Total‐Protein des Hodens. Plasma‐Na+ wurde nicht verändert. Ein flüchtiger Abfall des Plasma‐K+ ergab sich innerhalb von 2 Wochen Anwendung, während nach 4 Wochen ein Normalstatus wieder erreicht war. Die Hodenhistologie war erst nach 4 Wochen G‐Therapie deutlich beeinflußt im Sinne einer Spermatogenese‐hemmung. Die Motilität der Spermatozoen aus dem vas deferens war ebenfalls deutlich nach 4 Wochen herabgesetzt. Es wird festgestellt, daß aufgrund der gegenwärtigen Forschungsergebnisse ganz klar der Nachweis geführt werden kann, wonach Gossypol direkt die Spermatozoen beeinflußt und wonach Gossypol die ATPase‐Aktivität störend beeinflußt.

Studies on the Male Antifertility Agent Gossypol Acetic Acid VII. Effect of Motility Stimulated Factors on the Revival of Human Spermatozoal Motility after Gossypol Treatment in vitro

“…Our observations are further supported by the fact that radioactive gossypol binds to the spermatozoa very strongly and the radioactivity cannot be removed by repeated washing (unpublished). It has been reported by us earlier that gossypol inhibits the activity of ATPase in human spermatozoa (Kalla and Vasudev -1981). The finding that gossypol inhibits ATPase activity suggests that inhibition of sperm motility observed in the present investigations can be attributed, in part, to impairment in the utilization of ATP as a source of energy.…”

“…contraceptive pill in People's Republic of China. The mechanism of action of gossypol acetic acid on male germ cells is not known, but it has been reported by a number of workers that gossypol inhibits the motility of spermatozoa (National Coordinating Group -1978; Wang and Lei -1979;Kalla andVasudev -1980,1981;Kalla et al -1981Kalla et al - ,1982Hadley et al -1981). A number of enzymes associated with structural and functional integrity of spermatozoa have been reported to be affected by gossypol treatment (Adeyemo et al -1981;Tso et al -1982;Kalla -1982).…”

Studies on the Male Antifertility Agent - Gossypol Acetic Acid. V. Effect of Gossypol Acetic Acid on the Fertility of Male Rats

“…Our concept that gossypol does not interfere in the androgen biosynthesis in the testes is further strengthened by the observations that plasma LH and testosterone levels remain normal after gossypol treatment (Wang et al -1979a, b;Sunderam -1980;Liou -1981;Frick et al -1981 of LH and testosterone in rat after gossypol(30 mg/kg body weight/day for 4 weeks) treatment (Hadley et al -1981). We have reported earlier that gossypol treatment does not affect the activity of SDH, both in vivo and in vitro, in testes (Kalla and Vasudev -1980;Kalla and Foo -1981). These two factors have been reported to play an important role in mediating the gossypol effect on the fertility of male rats (Zatuchni and Osborn -1980).…”

Spermatotoxic effects of Cananga odorata (Lam): a comparison with gossypol

“…This yellow pigment permeates cells and acts as an inhibitor for several dehydrogenase enzymes and has been tested as male contraceptive. But hypokalemia, a major side effect, was discovered in gossypol-treated animals (2). We compared the spermatotoxicity of a 50% ethanolic extract of the root bark of Cananga odorata with gossypol.…”