Open Science Research Excellence

Open Science Index

Commenced in January 2007 Frequency: Monthly Edition: International Publications Count: 29284

Select areas to restrict search in scientific publication database:
Oxidative and Hormonal Disruptions Underlie Bisphenol A - Induced Testicular Toxicity in Male Rabbits
The presence of endocrine-disrupting compounds, such as bisphenol A (BPA), in the environment can cause serious health problems. However, there are controversial opinions. This study investigated the reproductive, metabolic, oxidative and immunologic-disrupting effects of bisphenol A in male rabbits. Rabbits were divided into five groups. The first four rabbit groups were administered oral BPA (1, 10, 50, or 100 mg/kg/day) for ten weeks. The fifth group was administered corn oil as the vehicle. BPA significantly decreased serum testosterone, estradiol and the free androgen index (FAI) and significantly increased sex hormone binding globulin (SHBG) compared with the placebo group. The higher doses of BPA showed a significant decrease in follicular stimulating hormone (FSH) and luteinizing hormone (LH). A significant increase in blood glucose levels was identified in the BPA groups. The non-significant difference in insulin levels is a novel finding. The cumulative testicular toxicity of BPA was clearly demonstrated by the dose-dependent decrease in absolute testes weight, primary measures of semen quality and a significant increase in testicular malonaldehyde (MDA). Moreover, BPA significantly decreased total antioxidant capacity (TAC) and significantly increased immunoglobulin G (IgG) at the highest concentration. Our results suggest that BPA, especially at higher doses, is associated with many adverse effects on metabolism, oxidative stress, immunity, sperm quality and markers of androgenic action.
Digital Object Identifier (DOI):


[1] L.N. Vandeberg, M.V. Maffini, C. Sonnenschein, B.S. Rubin, A.M. Soto, Bisphenol-A and the great divide: a review of controversies in the filed of endocrine disruption. Endocrine Review, vol. 30(1), pp. 75-95, 2009.
[2] US Environmental Protection Agency, Memorandum to EDSTAC Members RE: Definition of “Endocrine Disruptor”. Washington D.C., USA, 2007.
[3] A.K. Hotchkiss, C.V. Rider, C.R. Blystone, V.S. Wilson, P.C. Hartig, G.T. Ankley, P.M. Foster, C.L. Gray, Fifteen years after “wingspread” environmental endocrine disrupters and human and wildlife health: where we are today and where we need to go. Toxicology Sciences, vol. 105, pp. 235-259, 2008.
[4] I.R. Falconer, H.F. Chapman, M.R. Moore, G. Ranmuthugala, Endocrine-disrupting compounds: a review of their challenge to sustainable and safe water supply and water reuse. Environmental Toxicology, vol. 21, pp. 181-191, 2006.
[5] L.N. Vandenberg, Human exposure to bisphenol A. Reproductive Toxicology, vol. 24(2), pp. 139-177, 2007.
[6] A.M. Calafat, X. Ye, L.Y. Wong, J.A. Reidy, L.L. Needham, “Exposure of the U.S. Population to Bisphenol A and 4-tertiary-octylphenol: 2003- 2004,” Environ. Health Perspectives, vol. 116(1), pp. 39-44, 2008.
[7] C.S. Mazur, J.F. Kenneke, J.K. Hess-Wilson, J.C. Lipscomb, Differences between human and rat intestinal and hepatic bisphenol A glucuronidation and the influence of alamethicin on in vitro kinetic measurements. Drug Metabolism, vol. 38 (12), pp. 2232-2238, 2010.
[8] F.S. Vom Saal, “Chapel hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure,” Reproductive Toxicology, vol. 8, pp. 131-138, 2008.
[9] L.N. Vandenberg, T. Colborn, T.B. Hayes, “Hormones and endocrinedisrupting chemicals: low-dose effects and nonmonotonic dose responses.” Endocrine Review, vol. 6, pp. 254-261, 2012.
[10] S.H. Lam, M.M. Hlaing, X. Zhang, “Toxicogenomic and phenotypic analyses of bisphenol-A early-life exposure toxicity in zebrafish,” Plos One. Vol. 6 (12), pp. 282-289, 2011.
[11] L.C. Saalu, A.O. Adesanya, A.O. Oyewopo, Y. Raji, An evaluation of the deleterious effect of unilateral cryptorchidism on the contralateral normally descended testis. Scientific Research Essays, vol. 2(3), pp. 74- 78, 2007.
[12] WHO. World health organization laboratory manual for the examination of human semen and semen-cervical mucus interactions. 4th ed. Cambridge, UK/New York: Cambridge University Press, 1999.
[13] R.E. Chapin, J. Adams, K. Boekelheide, “NTP-CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A,” Birth Defects Research, vol. 83 (3), pp. 157–395, 2008.
[14] M. Razzoli, P. Valsecchi, P. Palanza, “Chronic exposure to low doses bisphenol A interferes with pair-bonding and exploration in female Mongolian gerbils,” Brain Reseach Bulletin, vol. 65 (3), pp. 249–254 , 2005.
[15] K. Yamasaki, M. Sawaki, S. Noda, N. Imatanaka, M. Takatsuki, “Subacute oral toxicity study of ethynylestradiol and bisphenol A, based on the draft protocol for the ‘enhanced OECD test guideline no. 407’. Archive Toxicology, vol. 76 (2), pp. 65–74, 2002.
[16] F. Lahnsteiner, B. Berger, M. Kletz, T. Weismann, Effect of Bisphenol A on maturation and quality of semen and eggs in the brown trout, Salmo trutta f. fario. Aquatic Toxicology, vol. 75, pp. 213-224, 2005.
[17] P. Labadie, H. Budzinski, Alteration of steroid hormone balance in juvenile turbot (Psetta maxima) exposed to nonylphenol, bisphenol A, tetrabromodiphenyl ether 47, diallylphthalate, oil, and oil spiked with alkylphenols. Archive Environmental Contamination Toxicology, vol. 50, pp. 552-561, 2006.
[18] E. Haubruge, F. Petit, M.J. Gage, Reduced sperm counts in guppies (Poecilia reticulata) following exposure to low levels of tributylin and bisphenol A. Biologial Sciences, vol. 1459, pp. 2333-2337, 2000.
[19] C.A. Richter, L.S. Birnbaum, F. Farabollini, R.R. Newbold, B.S. Rubin, C.E. Talsness, In vivo effects of bisphenol A in laboratory rodent studies. Reproductive Toxicology, vol. 24, pp. 199–224, 2007.
[20] C.B. Herath, W. Jin, G. Watanabe, K. Arai, A.K. Suzuki, K. Taya, Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats. Endocrine. Vol. 25, pp. 163–172, 2004.
[21] A. Tohei, S. Suda, K. Taya, T. Hashimoto, H. Kogo, Bisphenol A inhibits testicular functions and increases luteinizing hormone secretion in adult male rats. Experimental Biological Medicine, vol. 226, pp. 216– 221, 2001.
[22] A. Norazit, J. Mohamad, S. Abdul Razak, M.A. Abdulla, A. Azmil, M.A. Mohd, Effects of soya bean extract, bisphenol A and 17β-estradiol on the testis and circulating levels of testosterone and estradiol among peripubertal juvenile male sprague-dawley rats. Sains Malaysiana, vol. 41(1), pp. 63–69, 2012.
[23] O. Takahashi, S. Oishi, Testicular toxicity of dietary or parenterally administered bisphenol A in rats and mice. Food and Chemical Toxicology, vol. 41, pp. 1035-1044, 2003.
[24] Y. Toyama, S. Yuasa, Effects of neonatal administration of 17β- estradiol, β-estradiol 3-benzoate, or bisphenol A on mouse and rat spermatogenesis. Reproductive Toxicology, vol. 19, pp. 181-188, 2004.
[25] A. Hossaini, M. Dalgaard, A.M. Vinggaard, P. Pararinen, J.J. Larsen, Male reproductive effects of octylphenol and estradiol in Fischer and Wistar rats. Reproductive Toxicology, vol. 17, pp. 607-615, 2003.
[26] M. Furuya, F. Sasaki, A.M.A. Hassanin, S. Kuwahara, Y. Tsukamoto, Effects of bisphenol-A on the growth of comb and testes of male chicken. Candian Journal of Veterinary Research, vol. 67, pp. 68-71, 2002.
[27] T. Hanaoka, N. Kawamura, K. Hara, S. Tsugane, Urinary bisphenol A and plasma hormone concentrations in male workers exposed to bisphenol A diglycidyl ether and mixed organic solvents. Occupational Environmental Medicine, vol. 59, pp. 625–628, 2002.
[28] J.D. Meeker, A.M. Calafat, R. Hauser, Urinary bisphenol A concentrations in relation to serum thyroid and reproductive hormone levels in men from an infertility clinic. Environmental Science Technology, vol. 44, pp. 1458–1463, 2010.
[29] R.M. Sharpe, N.E. Skakkebaek, Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertility and Sterility, vol. 89(2), pp. 33–38, 2008.
[30] RJ. Witorsch, Endocrine disruptors: can biological effects and environmental risks be predicted? Regulatory Toxicology and Pharmacology vol. 36, pp. 118-130, 2002.
[31] R.W. Stahlhut, W.V. Welshons, S.H. Swan, Bisphenol-A data in NHANES suggest longer than expected half-life, substantial nonfood exposure, or both. Environmental Health Perspective, vol. 117, pp. 784- 789, 2009.
[32] R. Urbatzka, A. van Cauwenberge, S. Maggioni, L. Viganò, A. Mandich, E. Benfenati, I. Lutz, W. Kloas, Androgenic and antiandrogenic activities in water and sediment samples from the river Lambro, Italy, detected by yeast androgen screen and chemical analyses. Chemosphere, vol. 67, pp. 1080-1087, 2007.
[33] G. Pelletier, Localization of androgen and estrogen receptors in rat and primate tissues. Histology and Histopathology, vol. 15, pp. 1261–1270, 2000.
[34] J.S. Finkelstein, O’Dea, L.S. R.W. Whitcomb, W.F. Crowley, Sex steroid control of gonadotropin secretion in the human male. II. Effects of estradiol administration in normal and gonadotropin-releasing hormone-deficient men. Journal Clinical Endocrinology Metabolism, vol. 73, pp. 621–628, 1991.
[35] B.T. Akingbemi, C.M. Sottas, A.I. Koulova, G.R. Klinefelter, M.P. Hardy, Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology, vol. 145, pp, 592–603, 2004.
[36] Y.B. Wetherill, B.T. Akingbemi, J. Kanno, J.A. McLachlan, A. Nadal, C. Sonnenschein, In vitro molecular mechanisms of bisphenol A action. Reproductive Toxicology, vol. 24, pp. 178–198, 2007.
[37] D. Li, Z. Zhou, D. Qing, Y. He, T. Wu, M. Miao, Occupational exposure to bisphenol-A (BPA) and the risk of self-reported male sexual dysfunction. Human. Reproduction, vol. 25(2), pp. 519–527, 2010.
[38] K.C. Chitra, C. Latchoumycandane, P.P. Mathur, Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology, vol. 185, pp. 119-127, 2003.
[39] M. Aydoğan, A. Korkmaz, N. Barlas, D. Kolankaya, Pro-oxidant effect of vitamin C coadministration with bisphenol A, nonylphenol, and octylphenol on the reproductive tract of male rats. Drug Chemical Toxicology, vol. 33(2), pp. 193-203, 2010.
[40] P. Kovacic, How safe is bisphenol A? Fundamentals of toxicity: metabolism, electron transfer and oxidative stress. Medical Hypotheses, vol. 75(1), pp. 1-4, 2010.
[41] T. Takeuchi, O. Tsutsumi, Serum bisphenol A concentrations showed gender differences, possibly linked to androgen levels. Biochemistry Biophysics. Research Communication, vol. 291, pp. 76–78, 2002.
[42] K. Halldin, C. Berg, A. Bergman, I. Brandt, B. Brunström, Distribution of bisphenol A and tetrabromobisphenol A in quail eggs, embryos and laying birds and studies on reproduction variables in adults following in ovo exposure. Archive Toxicology, vol. 75, pp. 597-603, 2001.
[43] P. Nieminen, P. Lindstrom-Seppa, A. Mustonen, H. Mussalo-Rauhamaa, J.V.K. Kukkonen, Bisphenol A affects endocrine physiology and biotransformation enzyme activities of the field vole (Microtus agrestis). Gen. Comparative Endocrinology, vol. 126, pp. 183-189, 2002a.
[44] H. Kato, T. Furuhashi, M. Tanaka, Y. Katsu, H. Watanabe, Y. Ohta, T. Iguchi, Effects of bisphenol A given neonatally on reproductive functions of male rats. Reproductive Toxicology, vol. 22, pp. 20-29, 2006.
[45] E.P. Murono, R.C. Derk, J.H. de Leon, Differential effects of octylphenol, 17β-estradiol, endosulfan, or bisphenol A on the steroidogenic competence of cultured adult Leydig cells. Reproductive Toxicology, vol. 15, pp. 551-560, 2001.
[46] T.M. Batista, P. Onso-Magdalena, E. Vieira, M.E. Amaral, C.R. Cederroth, S. Nef, I. Quesada, E.M. Carneiro, A. Nadal, Short-term treatment with bisphenol-A leads to metabolic abnormalities in adult male mice. Plos One, vol. 7(3), pp. 338-344, 2012.
[47] S. Soriano, P. Alonso-Magdalena, M. García-Arévalo, A. Novials, S.J. Muhammed, Rapid insulinotropic action of low doses of bisphenol-a on mouse and human islets of langerhans: role of estrogen receptor β. PLos One. vol. 7(2), pp. 311-318, 2012.
[48] F.S. Vom Saal, S.C. Nagel, B.L. Coe, B.M. Angle, J.A. Taylor, The estrogenic endocrine disrupting chemical bisphenol A (BPA) and obesity. Moleculae Cell Endocrinology, vol. 354(1-2), pp. 74-84, 2012.
[49] I.A. Lang, T.S. A. Galloway, Scarlett, “Association of urinary bisphenol a concentration with medical disorders and laboratory abnormalities in adults.” Journal of American Medicine Association, vol. 11, pp. 1303- 1310, 2008.
[50] D. Melzer, "Urinary bisphenol: A concentration and risk of future coronary artery disease in apparently healthy men and women." Circulation, vol. 125(12), pp. 1482-90, 2012.
[51] E.R. Hugo, T.D. Brandebourg, J.G. Woo, “Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes,” Environmental Health Perspective, vol. 116 (12), pp. 1642-1647, 2008.
[52] S.C. D´ Cruz, R. Jubendradass, M. Jaykanthan, S.J.A. Rani, P.P. Mathur, Bisphenol A impairs insulin signalling and glucose homeostasis and decreases steroidogenesis in rat testis: An in vivo and in silico study. Food and Chemical Toxicology, vol. 1(1), pp. 41-49, 2011.
[53] S.A. Ahmed, The immune system as a potential target for environmental estrogens (endocrine disrupters): a new emerging field. Toxicology, vol. 150(1–3), pp. 191–206, 2000.
[54] H. Ishibashi, N. Matsumura, M. Hirano, M. Matsuoka, H. Shiratsuchi, Y. Ishibashi, Effects of triclosan on the early life stages and reproduction of medaka Oryzias latipes and induction of hepatic vitellogenin. Aquatic Toxicology, vol. 67(2), pp. 167–179, 2004.
[55] J.J. Segura, A. Jiménez-Rubio, R. Pulgar, N. Olea, Guerrero, J.M.; Calvo, J.R. In vitro effect of the resin component bisphenol A on substrate adherence capacity of macrophages. Journal Endocrinology, vol. 25(5), pp. 341–344, 1999.
[56] R.R. Dietert, J.C. Dewitt, D.R. Germolec, J.T. Zelikoff, Breaking patterns of environmentally influenced disease for health risk reduction: immune perspectives. Environmental Health Perspective, vol. 118, pp. 1091–1099, 2010.
Vol:13 No:02 2019Vol:13 No:01 2019
Vol:12 No:12 2018Vol:12 No:11 2018Vol:12 No:10 2018Vol:12 No:09 2018Vol:12 No:08 2018Vol:12 No:07 2018Vol:12 No:06 2018Vol:12 No:05 2018Vol:12 No:04 2018Vol:12 No:03 2018Vol:12 No:02 2018Vol:12 No:01 2018
Vol:11 No:12 2017Vol:11 No:11 2017Vol:11 No:10 2017Vol:11 No:09 2017Vol:11 No:08 2017Vol:11 No:07 2017Vol:11 No:06 2017Vol:11 No:05 2017Vol:11 No:04 2017Vol:11 No:03 2017Vol:11 No:02 2017Vol:11 No:01 2017
Vol:10 No:12 2016Vol:10 No:11 2016Vol:10 No:10 2016Vol:10 No:09 2016Vol:10 No:08 2016Vol:10 No:07 2016Vol:10 No:06 2016Vol:10 No:05 2016Vol:10 No:04 2016Vol:10 No:03 2016Vol:10 No:02 2016Vol:10 No:01 2016
Vol:9 No:12 2015Vol:9 No:11 2015Vol:9 No:10 2015Vol:9 No:09 2015Vol:9 No:08 2015Vol:9 No:07 2015Vol:9 No:06 2015Vol:9 No:05 2015Vol:9 No:04 2015Vol:9 No:03 2015Vol:9 No:02 2015Vol:9 No:01 2015
Vol:8 No:12 2014Vol:8 No:11 2014Vol:8 No:10 2014Vol:8 No:09 2014Vol:8 No:08 2014Vol:8 No:07 2014Vol:8 No:06 2014Vol:8 No:05 2014Vol:8 No:04 2014Vol:8 No:03 2014Vol:8 No:02 2014Vol:8 No:01 2014
Vol:7 No:12 2013Vol:7 No:11 2013Vol:7 No:10 2013Vol:7 No:09 2013Vol:7 No:08 2013Vol:7 No:07 2013Vol:7 No:06 2013Vol:7 No:05 2013Vol:7 No:04 2013Vol:7 No:03 2013Vol:7 No:02 2013Vol:7 No:01 2013
Vol:6 No:12 2012Vol:6 No:11 2012Vol:6 No:10 2012Vol:6 No:09 2012Vol:6 No:08 2012Vol:6 No:07 2012Vol:6 No:06 2012Vol:6 No:05 2012Vol:6 No:04 2012Vol:6 No:03 2012Vol:6 No:02 2012Vol:6 No:01 2012
Vol:5 No:12 2011Vol:5 No:11 2011Vol:5 No:10 2011Vol:5 No:09 2011Vol:5 No:08 2011Vol:5 No:07 2011Vol:5 No:06 2011Vol:5 No:05 2011Vol:5 No:04 2011Vol:5 No:03 2011Vol:5 No:02 2011Vol:5 No:01 2011
Vol:4 No:12 2010Vol:4 No:11 2010Vol:4 No:10 2010Vol:4 No:09 2010Vol:4 No:08 2010Vol:4 No:07 2010Vol:4 No:06 2010Vol:4 No:05 2010Vol:4 No:04 2010Vol:4 No:03 2010Vol:4 No:02 2010Vol:4 No:01 2010
Vol:3 No:12 2009Vol:3 No:11 2009Vol:3 No:10 2009Vol:3 No:09 2009Vol:3 No:08 2009Vol:3 No:07 2009Vol:3 No:06 2009Vol:3 No:05 2009Vol:3 No:04 2009Vol:3 No:03 2009Vol:3 No:02 2009Vol:3 No:01 2009
Vol:2 No:12 2008Vol:2 No:11 2008Vol:2 No:10 2008Vol:2 No:09 2008Vol:2 No:08 2008Vol:2 No:07 2008Vol:2 No:06 2008Vol:2 No:05 2008Vol:2 No:04 2008Vol:2 No:03 2008Vol:2 No:02 2008Vol:2 No:01 2008
Vol:1 No:12 2007Vol:1 No:11 2007Vol:1 No:10 2007Vol:1 No:09 2007Vol:1 No:08 2007Vol:1 No:07 2007Vol:1 No:06 2007Vol:1 No:05 2007Vol:1 No:04 2007Vol:1 No:03 2007Vol:1 No:02 2007Vol:1 No:01 2007