Reproductive Toxicity of Bisphenol A (BPA) in Albino Rats
This study evaluates the effect of oral administration of BPA on male reproductive parameters and female reproductive hormones. Male and female rats were evenly distributed to get 6 groups (5 rats per group) the first three groups were all male rats while the remaining three groups were female rats. BPA doses of 50 and 250mg/kg body weight were administered weekly to groups II, III, V and VI respectively while groups I and IV served as vehicle control. After 6 weeks of exposure, epididymis and blood samples were collected for semen and biochemical analysis. The parameters analysed include; actively motile sperm cells, dead cells, total sperm count, sluggishly motile cells, abnormal cells, viable cells, estradiol, prolactin and progesterone. The reproductive studies on male rats revealed that there was a significant reduction (p<0.05) in the percentage of actively motile sperm cells (93.33 -72.33), total sperm count 600.00% - 327.67%, while viable cells counts ranged from 82.67% to 67.33%. Dead sperm cells increased significantly from the control group (9.00%) to group 3 (19.67%), abnormal cells increased from the control at (22.00%) to group 3 (35.33%) while sluggishly motile cells increased in the same sequence (5.67% to 19.00%). Results on the female reproductive hormones showed that there was a steady reduction sequence from the control group to BPA-treated groups (group 3) at (p<0.05) in all parameters; with estradiol (84.00 to 68.00), prolactin (5.84 to 0.34) and progesterone (43.85 to 23.11). Results from this study indicate that exposure to BPA resulted in insidious alteration in female reproductive hormones and can also induce impotency in males.
(2) Agarwal A, Virk G, Ong C, du Plessis SS (2014). Effect of oxidative stress on male reproduction. World J Mens Health 32:1-17.
(3) Aitken RJ, Paterson M, Fisher H, Buckingham DW, van Duin M. (1995). Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J Cell Sci 108 (5) 2017-2025
(4) Amann, R. P. (1986). Detection of alteration in testicular and epididymal function in laboratory animals. Environmental Health Perspective, 70, 119-158.
(5) Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. (2017). The impact of oxidative stress on testicular function and the role of antioxidants in improving it: a review. J Clin Diagn Res 11: 01- 5
(6) Biedermann, S., Tschudin, P. and Grob, K. (2010). Transfer of bisphenol A from thermal printer paper to the skin. Analytical and Bioanalytical Chemistry, 398(1), 571-576.
(7) Correia, S., Oliveira, P. F., Guerreiro, P. M., Lopes, G., Alves, M. G., Canário, A. V., Cavaco, J. E. and Socorro, S. (2013). Sperm parameters and epididymis function in transgenic rats overexpressing the Ca2+-binding protein regucalcin: A hidden role for Ca2+ in sperm maturation? Mol. Hum. Reprod., 19, 581-589.
(8) De Lamirande E, and Gagnon C. (1995). Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum Reprod 10 (1)15-21
(9) Fernandez, M., Bianchi, M., Lux-Santos, V. and Libertun, C. (2009). Neonatal exposure to bisphenol A alters reproductive parameters and gonadotropin releasing hormone signaling in female rats. Environmental Health Perspectives, 117(5), 757-762.
(10) Hejmej A., M. Kotula-Balak, and B. Bilinsk, (2011). “Antiandrogenic and estrogenic compounds: effect on development and function of male reproductive system,” in Steroids – Clinical Aspect.
(11) Ho, S. M., Tang, W. Y., Belmonte, J. and Prins, G. S. (2006). Developmental exposure to estradiol and bisphenol A increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Resources, 66, 5624.
(12) Hulak, M., Gazo, I., Shaliutina, A., Linhartova, P. (2013). In vitro effects of bisphenol A on the quality parameters, oxidative stress, DNA integrity and adenosine triphosphate content in sterlet (Acipenser ruthenus) spermatozoa. Comparative Biochemistry and Physiology C: Toxicology and Pharmacology, 158 (2), 64–71.
(13) Huo, X., Chen, D., He, Y., Zhu, W., Zhou, W. and Zhang, J. (2015). Bisphenol-A and female infertility: a possible role of gene environment interactions. International Journal of Environmental Research and Public Health, 12(9), 11101–11116.
(14) Isling, L. K., Boberg, J., Jacobsen, P. R., Mandrup, K. R., Axelstad, M., Christiansen, S., Vinggaard, A. M., Taxvig, C., Kortenkamp, A. and Hass, U. (2014). Late life effects on rat reproductive system after development exposure to mixture of endocrine disruptors. Reproduction, 147(4), 465-476.
(15) Jin, P., Wang, X., Chang, F., Bai, Y., Li, Y., Zhou, R. and Chen, L. (2013). Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats. The Journal of Biomedical Research, 27(2), 135-144.
(16) Lassen T. H., H. Frederiksen, T. K. Jensen (2014). “Urinary bisphenol a levels in young men: Association with reproductive hormones and semen quality,” Environmental Health Perspectives, 122(5) 478–484.
(17) Karnam, S. S., Ghosh, R. C., Mondal, S. and Mondal, M. (2015). Evaluation of subacute bisphenol -A toxicity on male reproductive system. Veterinary World, 8, 2231-2916.
(18) Kourouma, A., Peng, D., Chao, Q., Changjiang, L., Chengmin, W., Wenjuan, F., Suqin, Q., Tingting, Y. and Kedi, Y. (2014). Bisphenol A induced reactive oxygen species (ROS) in the liver and affect epididymal semen quality in adults Sprague-Dawley rats. Journal of Toxicology and Environmental Health Science, 6, 103–112.
(19) Lang, I. A., Galloway, T. S., Scarlett, A., Henley, W. E., Depledge, M. and Wallace, R. B. (2008). Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. The Journal of the American Medical Association, 300, 1303.
(20) Le, H. H., Carlson, E. M., Chua, J. P. and Belcher, S.M. (2008). Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicology Letters, 176, 149-156.
(21) Lee, S. G., Kim, J. Y. and Chung, J. Y. (2013). Bisphenol a exposure during adulthood causes augmentation of follicular atresia and luteal regression by decreasing 17𝛽-estradiol synthesis via down regulation of aromatase in rat ovary. Environmental Health Perspectives, 121(6), 663–669.
(22) Li, D. K., Zhou, Z., Miao, M., He, Y., Wang, J., Ferber, J., Herrinton, L. J., Gao, E. and Yuan, W. (2011). Urine bisphenol A (BPA) level in relation to semen quality. International Journal of Fertility and Sterility, 95(2), 625-630.
(23) Luke, L., Vicens, A., Tourmente, M. and Roldan, E. R. (2014). Evolution of protamine genes and changes in sperm head phenotype in rodents. Biology of Reproduction, 90, 67.
(24) Matuszczak, E., Komarowska, D. M., Debek, W. and Hermanowicz, A. (2019). The impact of bisphenol a on fertility, reproductive system, and development: a review of the literature. International Journal of Endocrinology, 8.
(25) Manfo, F. P., Jubendradass, R., Nantia, E. A., Moundipa, P. F. and Mathur, P. P. (2014). Adverse effects of bisphenol A on male reproductive function. Reviews of Environmental Contamination and Toxicology, 228: 57-82.
(26) Meeker, J. D., Ehrlich, S., Toth, T. L., Wright, D. L., Calafat, A. M., Trisini, A. T. and Hauser, R. (2010). Semen quality and sperm DNA damage in relation to urinary bisphenol A among men from an infertility clinic. Reproductive Toxicology, 30, 532–539.
(27) Monje, L. Varayoud, J. Munoz-de-Toro, M. Luque, E. H. and Ramos, J. G. (2010). Exposure of neonatal female rats to bisphenol A disrupts hypothalamic LHRH pre-mRNA processing and estrogen receptor alpha expression in nuclei control lingestrous cyclicity. Reproductive Toxicology, 30(4), 625–634.
(28) Norwitz ER, Schust DJ, Fisher S. J. (2001). Implantation and the survival of early pregnancy. N Engl J Med. 345:1400–8
(29) O'Connell M., N. McClure, and S. E. M. Lewis, (2002). “The effects of cryopreservation on sperm morphology, motility and mitochondrial function,” Human Reproduction, 17(3)704–709.
(30) Patisaul, H. B., Fortino, A. E. and Polston, E. K. (2007). Differential disruption of nuclear volume and neuronal phenotype in the preoptic area by neonatal exposure to genistein and bisphenol A. Neurotoxicology, 28, 1.
(31) Qiu, L. L., Wang, X., Zhang, X. H., Zhang, Z., Gu, J., Liu, L., Wang, Y., Wang, X. and Wang, S. L. (2013). Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A. Toxicological Letters, 219(2), 116-124.
(32) Rahman MS, Kwon WS, Lee JS, Kim J, Yoon SJ, Park YJ, (2014). Sodium nitroprusside suppresses male fertility in vitro. Andrology 2:899-909.
(33) Rahman, M. S. and Pang, M. G. (2019). Understanding the molecular mechanisms of bisphenol A action in spermatozoa. Clin Exp Reprod Med 46(3) 99-106
(34) Saalu, L. C., Kpela, T., Benebo, A. S., Oyewopo, A. O., Anifowope, E. O. and Oguntola, J. A. (2010). The dose-dependent testiculoprotective and testiculotoxic potentials of telfairia occidentalis hook f. Leaves extract in rat. International Journal Applied Research in Natural Products, 3, 27-38.
(35) Salian, S., Doshi, T. and Vanage, G. (2009) Neonatal exposure of male rats to bisphenol A impairs fertility and expression of sertoli cell junctional proteins in the testis. Toxicology, 265(1-2), 56-67.
(36) Salian, S., Doshi, T. and Vanage, G. (2011). Perinatal exposure of rats to bisphenol A affects fertility of male offspring an overview. Reproductive Toxicology, 31 359–362. (doi:10.1016/j.reprotox.2010.10.008).
(37) Sembulingam, K. and Sembulingam, P. (2012). Essentials of Medical Physiology (6th ed.). New Delhi: Jaypee Brothers Medical Publishers. 478-481.
(38) Shuo, X., Honglu, D., Mary, A. S., Xiao, S. and Xiaoqin, Y. (2011). Preimplantation exposure to bisphenol A (BPA) affects embryo transport, preimplantation embryo development and uterine receptivity in mice. Reproductive Toxicology, 32(4), 434-441.
(39) Sugiura-Ogasawara, M., Ozaki, Y., Sonta, S., Makino, T. and Suzumori, K. (2005). Exposure to bisphenol A is associated with recurrent miscarriage, Human Reproduction, 20, 2325.
(40) Tinwell, H., Haseman, J., Lefevre, P. A., Wallis, N. and Ashby, J. (2002). Normal sexual development of two strains of rat exposed in utero to low doses of bisphenol A. Toxicological Science, 68, 339.
(41) Vandenberg, L. N., Maffini, M. V., Sonnenschein, C., Rubin, B. S. and Soto, A. M. (2009). Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocrine Reviews, 30, 75-95.
(42) Vilela, J., Hartmann, A., Silva, E. F., Cardoso, T., Corcini, C. D., Varela-Junior, A. S., Martinez, P. E. and Colares, E. P. (2014). Sperm impairments in adult vesper mice (Calomys laucha) caused by in uteroexposure to bisphenol A. Andrologia, 46(9), 971-978.
(43) Wang, P., C. Luo, Q. Li, S. Chen, and Y. Hu, (2014). “Mitochondrion-mediated apoptosis is involved in reproductive damage caused by BPA in male rats,” Environmental Toxicology and Pharmacology, 38(3) 1025–1033.
(44) Wilcox AJ, Weinberg CR, O'Connor JF, (1988). Incidence of early loss of pregnancy. N Engl J Med. 319:189–94.
(45) Witorsch, R. J. (2002). Endocrine disruptors: can biological effects and environmental risks be predicted? Regulatory Toxicology and Pharmacology, 36, 118-130.
(46) Zhou W, F. Fang, W. Zhu, Z. Chen, Y. Du, and J. Zhang,( 2016). “Bisphenol A and ovarian reserve among infertile women with polycystic ovarian syndrome,” International Journal of Environmental Research and Public Health, 27 pp. 14.
(47) Zoeller, R. T., Bansal, R. and Parris, C. (2005). Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology, 146, 607.
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