The effect of gossypol acetate on the fertility of boars

December 6, 2022

Copyright (c) 2022 by the Author(s)

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How To Cite
Selected Style: APA
Torres, M., Balogun, K., Shirley, L., de Andrade, A. F. C., Stewart, K., Hu, K., Wang, X., & Machaty, Z. (2022). The effect of gossypol acetate on the fertility of boars. Acta Agraria Debreceniensis, 2, 47-55.
Received 2022-09-15
Accepted 2022-10-11
Published 2022-12-06

This study evaluated the effect of gossypol acetate, a potential antifertility compound, on semen quality and testicular histopathology of boars. Six boars were allotted into two experimental groups. Half of the animals were fed a diet that was supplemented with 2 mg of gossypol acetate per kg body weight per day for 9 weeks, control animals received a gossypol acetate-free feed. During the experimental period, semen was collected weekly from each boar and semen parameters were recorded. The animals were then euthanized, testicular samples were collected and histopathological examination of the testicular cells, as well as morphometrical analysis of the seminiferous tubules, were performed. The percentage of spermatozoa showing tail abnormalities increased significantly (P=0.017) in the semen of boars fed gossypol acetate-supplemented feed, while several other semen parameters deteriorated without showing statistical significance. Gossypol acetate supplementation also led to a decrease (P=0.042) in the number of spermatogonia in the seminiferous tubules and an increase (P=0.020) in the number of vacuoles in the seminiferous epithelium, consistent with changes seen in cases of male reproductive toxicity. In conclusion, gossypol acetate negatively affected a number of semen characteristics and also had detrimental effects on the histopathology of the testes.

  1. Alvarez, J.G.–Storey, B.T. (1982): Spontaneous lipid peroxidation in rabbit epididymal spermatozoa: its effect on sperm
  2. motility. Biol. Reprod., 27, 1102–1108.
  3. Alvarez, J.G–Storey, B.T. (1985): Spontaneous lipid peroxidation in rabbit and mouse epididymal spermatozoa: dependence of rate on temperature and oxygen concentration. Biol. Reprod., 32, 342–351.
  4. Balakrishnan, K.–Wierda, W.G.–Keating, M.J.–Gandhi, V. (2008): Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood, 112, 1971–1980.
  5. Beaudoin, A.R. (1985): A reproduction and teratology study with gossypol. In: Gossypol. A potential contraceptive for men; Segal, S.J. Ed.; Plenum Press: New York, USA, pp. 89–109.
  6. Bernard, J.K.–Woldeghebriel, A.–Mueller, T.C. (2001): Nutrient intake and digestibility of cotton gin trash treated with hypochlorite oxidant or extruded. J. Appl. Anim. Res., 19, 165–176.
  7. Calamera, J.C.–Brugo, S.–Vilar, O. (1982): Relation between motility and adenosinetriphosphate (ATP) in human spermatozoa. Andrologia, 14, 239–241.
  8. Chang, M.C.–Gu, Z.–Saksena, S.K. (1980): Effects of gossypol on the fertility of male rats, hamsters and rabbits. Contraception, 21, 461–469.
  9. Chenoweth, P.J.–Chase, C.C.–Risco, C.A.–Larsen, R.E. (2000): Characterization of gossypol-induced sperm abnormalities in bulls. Theriogenology, 53, 1193–1203.
  10. Chenoweth, P.J.–Risco, C.A.–Larsen, R.E.–Velez, J.–Tran, T.–Chase, Jr. C.C. (1994): Effects of dietary gossypol on aspects of semen quality, sperm morphology and sperm production in young Brahman bulls. Theriogenology, 42, 1–13.
  11. Coutinho, E.M. (2002): Gossypol: a contraceptive for men. Contraception, 65, 259–263.
  12. Coutinho, E.M.–Athayde, C.–Atta, G.–Gu, Z.P.–Chen, Z.W.–Sang, G.W.–Emuveyan, E.–Adekunle, A.O.–Mati, J.–Otubu, J.–Reidenberg, M.M.–Segal, S.J. (2000): Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study. Contraception, 61, 61–67.
  13. Creasy, D.M. (2001): Pathogenesis of male reproductive toxicity. Toxicol. Pathol., 29, 64–76.
  14. D’Cruz, S.C.–Vaithinathan, S.–Jubendradass, R.–Mathur, P.P. (2010): Effects of plants and plant products on the testis. Asian J. Androl., 12, 468–479.
  15. du Plessis, S.S.–Agarwal, A.–Mohanty, G.–van der Linde, M. (2015): Oxidative phosphorylation versus glycolysis: What fuel do spermatozoa use? Asian J. Androl., 17, 230–235.
  16. EL-Mokadem, M.Y.–Taha, T.A.–Samak, M.A.–Yassen, A.M. (2012): Alleviation of reproductive toxicity of gossypol using selenium supplementation in rams. J. Anim. Sci., 90, 3274–3285.
  17. El-Sharaky, A.S.–Newairy, A.A.–Elguindy, N.M.–Elwafa, A.A. (2010): Spermatotoxicity, biochemical changes and histological alteration induced by gossypol in testicular and hepatic tissues of male rats. Food Chem. Toxicol., 48, 3354–3361.
  18. Esposito, G.–Jaiswal, B.S.–Xie, F.–Krajnc-Franken, M.A.–Robben, T.J.–Strik, A.M.–Kuil, C.–Philipsen, R.L.A.–van Duin, M.–Conti, M.–Gossen., J.A. (2004): Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proc. Natl. Acad. Sci. USA., 101, 2993–2998.
  19. França, L.R.–Avelar, G.F.–Almeida, F.F.L. (2005): Spermatogenesis and sperm transit through the epididymis in mammals with emphasis on pigs. Theriogenology, 63, 300–318.
  20. Gadelha, I.C.–Fonseca, N.B.–Oloris, S.C.–Melo, M.M.–Soto-Blanco, B. (2014): Gossypol toxicity from cottonseed products. Scientific World Journal, 231635.
  21. Gåfvels, M.–Wang, J.–Bergh, A.–Damber, J.E.–Selstam, G. (1984): Toxic effects of the antifertility agent gossypol in male rats. Toxicology, 32, 325–333.
  22. Guedes, F.–Soto-Blanco, B. (2011): Effects of gossypol present in cottonseed cake on spermatogenesis in sheep. In Poisoning by plants, mycotoxins and related toxins, Riet-Correa, F., Pfister, J., Schild, A.L., Wierenga, T., Eds.; CAB International: Wallingford, UK, pp. 285–288.
  23. Guo, H.–Gong, Y.–He, B.–Zhao, R. (2017): Relationships between mitochondrial DNA content, mitochondrial activity, and boar sperm motility. Theriogenology, 87, 276–283.
  24. Hahn, D.W.–Rusticus, C.–Probst, A.–Homm, R.–Johnson, A.N. (1981): Antifertility and endocrine activities of gossypol in rodents. Contraception, 24, 97–105.
  25. Hassan, M.E.–Smith, G.W.–Ott, R.S.–Faulkner, D.B.–Firkins, L.D.–Ehrhart, E.J.–Schaeffer, D.J. (2004): Reversibility of the reproductive toxicity of gossypol in peripubertal bulls. Theriogenology, 61, 1171–1179.
  26. Heywood, R.–Lloyd, G.K.–Majeed, S.K.–Gopinath, C. (1986): The toxicity of gossypol to the male rat. Toxicology, 40, 279-284.
  27. Jiang, J.–Slivova, V.–Jedinak, A.–Sliva, D. (2012): Gossypol inhibits growth, invasiveness, and angiogenesis in human prostate cancer cells by modulating NF-κB/AP-1 dependent- and independent-signaling. Clin. Exp. Metastasis, 29, 165–178.
  28. Jones, R.–Mann, T. (1977): Damage to ram spermatozoa by peroxidation of endogenous phospholipids. J. Reprod. Fertil., 50, 261–268.
  29. Kalla, N.R.–Grewal, R.–Ranga, A.–Sharma, R.K.–Khaira, P. (1990): Spermatogenic events in rat and mice following intratesticular administration of optical isomers of gossypol. Acta. Eur. Fertil., 21, 91–94. PMID: 2087944
  30. Kanwar, U.–Kaur, R.–Chadha, S.–Sanyal, S. (1990): Gossypol-induced inhibition of glucose uptake in human ejaculated spermatozoa may be mediated by lipid peroxidation. Contraception, 42, 573–587.
  31. Kovacic, P. (2003): Mechanism of drug and toxic actions of gossypol: focus on reactive oxygen species and electron transfer. Curr. Med. Chem., 10, 2711–2718.
  32. Lan, Z.J.–Gu, Z.P.–Lu, R.F.–Zhuang, L.Z. (1992): Effects of multiglycosides of Tripterygium wilfordii (GTW) on rat fertility and Leydig and Sertoli cells. Contraception, 45, 249–261.
  33. Morgan, S.E. (1989): Gossypol as a toxicant in livestock. In: The veterinary clinics of North America: Food Animal Practice; Burrows, G.E., Ed.; W.B. Saunders: Philadelphia, USA, pp. 251–263.
  34. National Coordinating Group on Male Antifertility Agents (China). (1979): Gossypol - a new antifertility agent for males. Gynecol Obstet Invest, 10.
  35. Nunes, F.D.C.R.–De Araujo, D.A.F.V.–Bezerra, M.B.–Soto-Blanco, B. (2010): Effects of gossypol present in cottonseed cake on the spermatogenesis of goats. J. Anim. Vet. Adv., 9, 75–78.
  36. Randel, R.D.–Chase, C.C.–Wyse, S.J. (1992): Effects of gossypol and cottonseed products on reproduction of mammals. J. Anim. Sci., 70, 1628–1638.
  37. Saleh, S.R.–Attia, R.–Ghareeb, D.A. (2018): The ameliorating effect of berberine-rich fraction against gossypol-induced testicular inflammation and oxidative stress. Oxid. Med. Cell. Longev., 1056173.
  38. Santana, A.T.–Guelfi, M.–Medeiros, H.C.D.–Tavares, M.A.–Bizerra, P.F.V.–Mingatto, F.E. (2015): Mechanisms involved in reproductive damage caused by gossypol in rats and protective effects of vitamin E. Biol. Res., 48, 43.
  39. Segal, S.J. (1985): Introduction and history of gossypol. In: Gossypol, a potential contraceptive for men; Segal, S.J., Ed.; Plenum Press: New York, USA, pp. 1–7.
  40. Shaha, C.–Tripathi, R.–Mishra, D.P. (2010): Male germ cell apoptosis: regulation and biology. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 365, 1501–1515.
  41. Shi, Q.X.–Tso, W.W.–Friend, D.S. (1987): Gossypol inhibition of spermatogenesis, sperm motility and metabolism. In: New Horizons in Sperm Cell Research; Mohri, H., Ed.; Japan Sci. Soc. Press./Gordon and Breach. Sci. Publisher: New York, USA, pp. 389–408.
  42. Singla, N.–Garg, M. (2013): Effect of crude cottonseed oil containing gossypol on fertility of male and estrous cycle of female Bandicota bengalensis Gray and Hardwicke. J. Appl. Anim. Res., 41, 156–165.
  43. Srivastava, A.–Gupta, G.–Setty, B.S. (1989): Studies on mechanism(s) of antifertility action of gossypol in rat and hamster. Contraception, 39, 337–355.
  44. Stephens, D.T.–Critchlow, L.M.–Hoskins, D.D. (1983): Mechanism of inhibition by gossypol of glycolysis and motility of monkey spermatozoa in vitro. J. Reprod. Fertil., 69, 447–452.
  45. Tang, X.C.–Zhu, M.K.–Shi, Q.X. (1980): Comparative studies on the absorption, distribution and excretion of 14C-gossypol in four species of animals. Acta. Pharm. Sin., 15, 212–217. PMID: 6779501
  46. Tanyildizi, S.–Bozkurt, T. (2004): In vitro effects of linamarin, amygdalin and gossypol acetic acid on hyaluronidase activity, sperm motility and morphological abnormality in bull sperm. Turk. J. Vet. Anim. Sci., 28, 819–824.
  47. Ueno, H.–Sahni, M.K.–Segal, S.J.–Koide, S.S. (1988): Interaction of gossypol with sperm macromolecules and enzymes. Contraception, 37, 333–341.
  48. Van Poznak, C.–Seidman, A.D.–Reidenberg, M.M.–Moasser, M.M.–Sklarin, N.–Van Zee, K.–Borgen, P.–Gollub, M.–Bacotti, D.–Yao, T.J.–Bloch, R.–Ligueros, M.–Sonenberg, M.–Norton, L.–Hudis, C. (2001): Oral gossypol in the treatment of patients with refractory metastatic breast cancer: a phase I/II clinical trial. Breast Cancer Res. Treat., 66, 239–248.
  49. Wang, Y.-X.–Wang, P.–Feng, W.–Liu, C.–Yang, P.–Chen, Y.-J.–Sun, L.–Sun, Y.–Yue, J.–Gu, L.-J.–Zeng, Q.–Lu, W.-Q. (2017): Relationships between seminal plasma metals/metalloids and semen quality, sperm apoptosis and DNA integrity. Environ. Pollut., 224, 224–234.
  50. Wu, X.-R. (1972): Study of antifertility action of cottonseed and the effective component- gossypol. Proc. National Conference on Recent Advance of Family Planning Research, Beijing, China.
  51. Xue, S.P. (1980): Studies on the antifertility effect of gossypol, a new contraceptive for males. Proc. Recent Advances in Fertility Regulation, Beijing, China, pp. 122–146.
  52. Xue, S.P. (1985): Gossypol contraception and mechanism of action. In: Male fertility and its regulation, Lobl, T.J., Hafez, E.S.E. Eds.; Springer: Dordrecht, Netherlands, pp. 155–174.
  53. Zavos, P.M.–Zarmakoupis-Zavos, P.N. (1996): The inhibitory effects of gossypol on human sperm motility characteristics: possible modes of reversibility of those effects. Tohoku J. Exp. Med., 179, 167–715.