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Published in: Environmental Health and Preventive Medicine 1/2019

Open Access 01-12-2019 | Testosterone | Research article

Effect of bisphenol F, an analog of bisphenol A, on the reproductive functions of male rats

Authors: Asad Ullah, Madeeha Pirzada, Tayyaba Afsar, Suhail Razak, Ali Almajwal, Sarwat Jahan

Published in: Environmental Health and Preventive Medicine | Issue 1/2019

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Abstract

Objective

Bisphenol A (BPA) is a monomer primarily used in the production of polycarbonate plastic and epoxy resins. Bisphenol F (BPF) is apparently the main BPA replacement that is used increasingly. BPF has been detected in canned food, thermal paper receipts, and soft drinks. In the present experiment, we did both in vitro and in vivo studies to evaluate the effect of low and high-dose BPF exposures on testosterone concentration, oxidative stress, and antioxidants activity in reproductive tissues of male rats.

Methods

Adult (80–90 days old) male Sprague Dawley rats (n = 36) obtained from the rodent colony of Animal Sciences Department of Quaid-i-Azam University. The direct effects of BPF on the antioxidant enzymes and testosterone secretion were measured in vitro and in vivo studies. In an in vivo experiment, adult male Sprague Dawley rats (n = 42) were exposed to different concentrations of bisphenol F (1, 5, 25, and 50 mg/kg/d) for 28 days. Various biochemical parameters were analyzed including the level of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), reactive oxygen species (ROS), and lipid peroxidation (LPO). Moreover, sperm motility, daily sperm production (DSP), comet assay, and histological analysis were performed.

Results

In vitro study showed that BPF exposure significantly (p < 0.05) induced oxidative stress biomarkers, i.e., ROS and LPO, while it did not change antioxidant enzyme and testicular testosterone concentration. Whereas, an in vivo study revealed that BPF induced dose-dependent effect and high-dose (100 mg/kg) exposure of BPF significantly reduced tissue protein (p < 0.05) content, CAT (p < 0.001), SOD (p < 0.05), and POD (p < 0.05) levels while significantly (p < 0.05) augmented ROS and lipid peroxidation. Furthermore, BPF reduces testosterone, LH, and FSH secretion in a dose-dependent manner. Significant (p < 0.001) reduction in plasma and intra-testicular testosterone, LH, and FSH was noticed at 100 mg/kg BFP dose. High-dose exposure reduces spermatogenesis.

Conclusion

BPF showed an antagonistic effect on male reproductive hormones and induce alterations in testicular morphology. Increased oxidative stress and decreased testicular antioxidant status might be the underlying mechanism of BFP-induced testicular toxicity.
Literature
1.
go back to reference Geens T, Goeyens L, Covaci A. Are potential sources for human exposure to bisphenol-a overlooked? Int J Hyg Environ Health. 2011;214(5):339–47.CrossRef Geens T, Goeyens L, Covaci A. Are potential sources for human exposure to bisphenol-a overlooked? Int J Hyg Environ Health. 2011;214(5):339–47.CrossRef
2.
go back to reference Geens T, Apelbaum TZ, Goeyens L, Neels H, Covaci A. Intake of bisphenol A from canned beverages and foods on the Belgian market. Food Addit Contam. 2010;27(11):1627–37.CrossRef Geens T, Apelbaum TZ, Goeyens L, Neels H, Covaci A. Intake of bisphenol A from canned beverages and foods on the Belgian market. Food Addit Contam. 2010;27(11):1627–37.CrossRef
3.
go back to reference Kang J-H, Kondo F, Katayama Y. Human exposure to bisphenol A. Toxicol. 2006;226(2–3):79–89.CrossRef Kang J-H, Kondo F, Katayama Y. Human exposure to bisphenol A. Toxicol. 2006;226(2–3):79–89.CrossRef
4.
go back to reference Commission E. Commission Regulation (EU) No 10/2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food. Off J Eur Union. 2011;12:1–89. Commission E. Commission Regulation (EU) No 10/2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food. Off J Eur Union. 2011;12:1–89.
5.
go back to reference Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon H-B, Nakata H, Kannan K. Bisphenol S in urine from the United States and seven Asian countries: occurrence and human exposures. Environ Sci Technol. 2012;46(12):6860–6.CrossRef Liao C, Liu F, Alomirah H, Loi VD, Mohd MA, Moon H-B, Nakata H, Kannan K. Bisphenol S in urine from the United States and seven Asian countries: occurrence and human exposures. Environ Sci Technol. 2012;46(12):6860–6.CrossRef
6.
go back to reference Viñas P, Campillo N, Martínez-Castillo N, Hernández-Córdoba M. Comparison of two derivatization-based methods for solid-phase microextraction–gas chromatography–mass spectrometric determination of bisphenol A, bisphenol S and biphenol migrated from food cans. Anal Bioanal Chem. 2010;397(1):115–25.CrossRef Viñas P, Campillo N, Martínez-Castillo N, Hernández-Córdoba M. Comparison of two derivatization-based methods for solid-phase microextraction–gas chromatography–mass spectrometric determination of bisphenol A, bisphenol S and biphenol migrated from food cans. Anal Bioanal Chem. 2010;397(1):115–25.CrossRef
7.
go back to reference Rosenmai AK, Dybdahl M, Pedersen M, Alice van Vugt-Lussenburg BM, Wedebye EB, Taxvig C, Vinggaard AM. Are structural analogues to bisphenol a safe alternatives? Toxicol Sci. 2014;139(1):35–47.CrossRef Rosenmai AK, Dybdahl M, Pedersen M, Alice van Vugt-Lussenburg BM, Wedebye EB, Taxvig C, Vinggaard AM. Are structural analogues to bisphenol a safe alternatives? Toxicol Sci. 2014;139(1):35–47.CrossRef
8.
go back to reference Cirillo T, Latini G, Castaldi MA, Dipaola L, Fasano E, Esposito F, Scognamiglio G, Francesco FD, Cobellis L. Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol A through infant formulas. J Agric Food Chem. 2015;63(12):3303–10.CrossRef Cirillo T, Latini G, Castaldi MA, Dipaola L, Fasano E, Esposito F, Scognamiglio G, Francesco FD, Cobellis L. Exposure to di-2-ethylhexyl phthalate, di-n-butyl phthalate and bisphenol A through infant formulas. J Agric Food Chem. 2015;63(12):3303–10.CrossRef
9.
go back to reference Ye X, Kuklenyik Z, Needham LL, Calafat AM. Automated on-line column-switching HPLC-MS/MS method with peak focusing for the determination of nine environmental phenols in urine. Anal Chem. 2005;77(16):5407–13.CrossRef Ye X, Kuklenyik Z, Needham LL, Calafat AM. Automated on-line column-switching HPLC-MS/MS method with peak focusing for the determination of nine environmental phenols in urine. Anal Chem. 2005;77(16):5407–13.CrossRef
10.
go back to reference Ye X, Wong L-Y, Kramer J, Zhou X, Jia T, Calafat AM. Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of US adults during 2000–2014. Environ Sci Technol. 2015;49(19):11834–9.CrossRef Ye X, Wong L-Y, Kramer J, Zhou X, Jia T, Calafat AM. Urinary concentrations of bisphenol A and three other bisphenols in convenience samples of US adults during 2000–2014. Environ Sci Technol. 2015;49(19):11834–9.CrossRef
11.
go back to reference Cabaton N, Zalko D, Rathahao E, Canlet C, Delous G, Chagnon M-C, Cravedi J-P, Perdu E. Biotransformation of bisphenol F by human and rat liver subcellular fractions. Toxicol in Vitro. 2008;22(7):1697–704.CrossRef Cabaton N, Zalko D, Rathahao E, Canlet C, Delous G, Chagnon M-C, Cravedi J-P, Perdu E. Biotransformation of bisphenol F by human and rat liver subcellular fractions. Toxicol in Vitro. 2008;22(7):1697–704.CrossRef
12.
go back to reference Cabaton N, Dumont C, Severin I, Perdu E, Zalko D, Cherkaoui-Malki M, Chagnon M-C. Genotoxic and endocrine activities of bis (hydroxyphenyl) methane (bisphenol F) and its derivatives in the HepG2 cell line. Toxicol. 2009;255(1–2):15–24.CrossRef Cabaton N, Dumont C, Severin I, Perdu E, Zalko D, Cherkaoui-Malki M, Chagnon M-C. Genotoxic and endocrine activities of bis (hydroxyphenyl) methane (bisphenol F) and its derivatives in the HepG2 cell line. Toxicol. 2009;255(1–2):15–24.CrossRef
13.
go back to reference Gramec Skledar D, Troberg J, Lavdas J, Peterlin Mašič L, Finel M. Differences in the glucuronidation of bisphenols F and S between two homologous human UGT enzymes, 1A9 and 1A10. Xenobiotica. 2015;45(6):511–9.CrossRef Gramec Skledar D, Troberg J, Lavdas J, Peterlin Mašič L, Finel M. Differences in the glucuronidation of bisphenols F and S between two homologous human UGT enzymes, 1A9 and 1A10. Xenobiotica. 2015;45(6):511–9.CrossRef
14.
go back to reference Cabaton N, Chagnon M-C, Lhuguenot J-C, Cravedi J-P, Zalko D. Disposition and metabolic profiling of bisphenol F in pregnant and nonpregnant rats. J Agric Food Chem. 2006;54(26):10307–14.CrossRef Cabaton N, Chagnon M-C, Lhuguenot J-C, Cravedi J-P, Zalko D. Disposition and metabolic profiling of bisphenol F in pregnant and nonpregnant rats. J Agric Food Chem. 2006;54(26):10307–14.CrossRef
15.
go back to reference Hulak M, Gazo I, Shaliutina A, Linhartova P. In vitro effects of bisphenol A on the quality parameters, oxidative stress, DNA integrity and adenosine triphosphate content in sterlet (Acipenser ruthenus) spermatozoa. Comp Biochem Physiol Part C Toxicol Pharmacol. 2013;158(2):64–71.CrossRef Hulak M, Gazo I, Shaliutina A, Linhartova P. In vitro effects of bisphenol A on the quality parameters, oxidative stress, DNA integrity and adenosine triphosphate content in sterlet (Acipenser ruthenus) spermatozoa. Comp Biochem Physiol Part C Toxicol Pharmacol. 2013;158(2):64–71.CrossRef
16.
go back to reference Ullah H, Jahan S, Ain QU, Shaheen G, Ahsan N. Effect of bisphenol S exposure on male reproductive system of rats: a histological and biochemical study. Chemosphere. 2016;152:383–91.CrossRef Ullah H, Jahan S, Ain QU, Shaheen G, Ahsan N. Effect of bisphenol S exposure on male reproductive system of rats: a histological and biochemical study. Chemosphere. 2016;152:383–91.CrossRef
17.
go back to reference Ullah A, Pirzada M, Jahan S, Ullah H, Shaheen G, Rehman H, Siddique MF, Butt MA. Bisphenol A and its analogs bisphenol B, bisphenol F, and bisphenol S: comparative in vitro and in vivo studies on the sperms and testicular tissues of rats. Chemosphere. 2018;209:508–16.CrossRef Ullah A, Pirzada M, Jahan S, Ullah H, Shaheen G, Rehman H, Siddique MF, Butt MA. Bisphenol A and its analogs bisphenol B, bisphenol F, and bisphenol S: comparative in vitro and in vivo studies on the sperms and testicular tissues of rats. Chemosphere. 2018;209:508–16.CrossRef
18.
go back to reference Heindel JJ, Newbold RR, Bucher JR, Camacho L, Delclos KB, Lewis SM, Vanlandingham M, Churchwell MI, Twaddle NC, McLellen M. NIEHS/FDA CLARITY-BPA research program update. Reprod Toxicol. 2015;58:33–44.CrossRef Heindel JJ, Newbold RR, Bucher JR, Camacho L, Delclos KB, Lewis SM, Vanlandingham M, Churchwell MI, Twaddle NC, McLellen M. NIEHS/FDA CLARITY-BPA research program update. Reprod Toxicol. 2015;58:33–44.CrossRef
19.
go back to reference Ullah A, Pirzada M, Jahan S, Ullah H, Turi N, Ullah W, Siddiqui MF, Zakria M, Lodhi KZ, Khan MM. Impact of low-dose chronic exposure to bisphenol A and its analogue bisphenol B, bisphenol F and bisphenol S on hypothalamo-pituitary-testicular activities in adult rats: a focus on the possible hormonal mode of action. Food Chem Toxicol. 2018;121:24–36.CrossRef Ullah A, Pirzada M, Jahan S, Ullah H, Turi N, Ullah W, Siddiqui MF, Zakria M, Lodhi KZ, Khan MM. Impact of low-dose chronic exposure to bisphenol A and its analogue bisphenol B, bisphenol F and bisphenol S on hypothalamo-pituitary-testicular activities in adult rats: a focus on the possible hormonal mode of action. Food Chem Toxicol. 2018;121:24–36.CrossRef
20.
go back to reference Afsar T, Razak S. Modulatory influence of Acacia hydaspica R. Parker ethyl acetate extract against cisplatin inveigled hepatic injury and dyslipidemia in rats. BMC Complement Altern Med. 2017;17(1):307.CrossRef Afsar T, Razak S. Modulatory influence of Acacia hydaspica R. Parker ethyl acetate extract against cisplatin inveigled hepatic injury and dyslipidemia in rats. BMC Complement Altern Med. 2017;17(1):307.CrossRef
21.
go back to reference Afsar T, Razak S, Almajwal A, Khan MR. Acacia hydaspica R. Parker ameliorates cisplatin induced oxidative stress, DNA damage and morphological alterations in rat pulmonary tissue. BMC Complement Altern Med. 2018;18(1):49.CrossRef Afsar T, Razak S, Almajwal A, Khan MR. Acacia hydaspica R. Parker ameliorates cisplatin induced oxidative stress, DNA damage and morphological alterations in rat pulmonary tissue. BMC Complement Altern Med. 2018;18(1):49.CrossRef
22.
go back to reference Carlberg I, Mannervik E. Glutathione concentration in rat brain. J Biol Chem. 1975;250:4475–80. Carlberg I, Mannervik E. Glutathione concentration in rat brain. J Biol Chem. 1975;250:4475–80.
23.
go back to reference Iqbal M, Sharma S, Rezazadeh H, Hasan N, Abdulla M, Athar M. Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate mediated hepatic injury. Redox Rep. 1996;2(6):385–91.CrossRef Iqbal M, Sharma S, Rezazadeh H, Hasan N, Abdulla M, Athar M. Glutathione metabolizing enzymes and oxidative stress in ferric nitrilotriacetate mediated hepatic injury. Redox Rep. 1996;2(6):385–91.CrossRef
24.
go back to reference Hayashi I, Morishita Y, Imai K, Nakamura M, Nakachi K, Hayashi T. High-throughput spectrophotometric assay of reactive oxygen species in serum. Mutat Res Genet Toxicol Environ Mutagen. 2007;631(1):55–61.CrossRef Hayashi I, Morishita Y, Imai K, Nakamura M, Nakachi K, Hayashi T. High-throughput spectrophotometric assay of reactive oxygen species in serum. Mutat Res Genet Toxicol Environ Mutagen. 2007;631(1):55–61.CrossRef
25.
go back to reference Jensen EC. Quantitative analysis of histological staining and fluorescence using ImageJ. Anat Rec. 2013;296(3):378–81.CrossRef Jensen EC. Quantitative analysis of histological staining and fluorescence using ImageJ. Anat Rec. 2013;296(3):378–81.CrossRef
26.
go back to reference Lee HJ, Chattopadhyay S, Gong E-Y, Ahn RS, Lee K. Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen receptor. Toxicol Sci. 2003;75(1):40–6.CrossRef Lee HJ, Chattopadhyay S, Gong E-Y, Ahn RS, Lee K. Antiandrogenic effects of bisphenol A and nonylphenol on the function of androgen receptor. Toxicol Sci. 2003;75(1):40–6.CrossRef
27.
go back to reference Minatoya M, Itoh S, Miyashita C, Araki A, Sasaki S, Miura R, Goudarzi H, Iwasaki Y, Kishi R. Association of prenatal exposure to perfluoroalkyl substances with cord blood adipokines and birth size: the Hokkaido study on environment and children's health. Environ Res. 2017;156:175–82.CrossRef Minatoya M, Itoh S, Miyashita C, Araki A, Sasaki S, Miura R, Goudarzi H, Iwasaki Y, Kishi R. Association of prenatal exposure to perfluoroalkyl substances with cord blood adipokines and birth size: the Hokkaido study on environment and children's health. Environ Res. 2017;156:175–82.CrossRef
28.
go back to reference Kishi R, Araki A, Minatoya M, Hanaoka T, Miyashita C, Itoh S, Kobayashi S, Bamai YA, Yamazaki K, Miura R. The Hokkaido birth cohort study on environment and children’s health: cohort profile—updated 2017. Environ Health Prev Med. 2017;22(1):46.CrossRef Kishi R, Araki A, Minatoya M, Hanaoka T, Miyashita C, Itoh S, Kobayashi S, Bamai YA, Yamazaki K, Miura R. The Hokkaido birth cohort study on environment and children’s health: cohort profile—updated 2017. Environ Health Prev Med. 2017;22(1):46.CrossRef
29.
go back to reference Minatoya M, Itoh S, Yamazaki K, Araki A, Miyashita C, Tamura N, Yamamoto J, Onoda Y, Ogasawara K, Matsumura T. Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children’s Health. Environ Health Prev Med. 2018;23(1):43.CrossRef Minatoya M, Itoh S, Yamazaki K, Araki A, Miyashita C, Tamura N, Yamamoto J, Onoda Y, Ogasawara K, Matsumura T. Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children’s Health. Environ Health Prev Med. 2018;23(1):43.CrossRef
30.
go back to reference Eladak S, Grisin T, Moison D, Guerquin M-J, N'Tumba-Byn T, Pozzi-Gaudin S, Benachi A, Livera G, Rouiller-Fabre V, Habert R. A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertil Steril. 2015;103(1):11–21.CrossRef Eladak S, Grisin T, Moison D, Guerquin M-J, N'Tumba-Byn T, Pozzi-Gaudin S, Benachi A, Livera G, Rouiller-Fabre V, Habert R. A new chapter in the bisphenol A story: bisphenol S and bisphenol F are not safe alternatives to this compound. Fertil Steril. 2015;103(1):11–21.CrossRef
31.
go back to reference Wu M, Xu H, Shen Y, Qiu W, Yang M. Oxidative stress in zebrafish embryos induced by short-term exposure to bisphenol A, nonylphenol, and their mixture. Environ Toxicol Chem. 2011;30(10):2335–41.CrossRef Wu M, Xu H, Shen Y, Qiu W, Yang M. Oxidative stress in zebrafish embryos induced by short-term exposure to bisphenol A, nonylphenol, and their mixture. Environ Toxicol Chem. 2011;30(10):2335–41.CrossRef
32.
go back to reference Maćczak A, Cyrkler M, Bukowska B, Michałowicz J. Eryptosis-inducing activity of bisphenol A and its analogs in human red blood cells (in vitro study). J Hazard Mater. 2016;307:328–35.CrossRef Maćczak A, Cyrkler M, Bukowska B, Michałowicz J. Eryptosis-inducing activity of bisphenol A and its analogs in human red blood cells (in vitro study). J Hazard Mater. 2016;307:328–35.CrossRef
33.
go back to reference Holdcraft RW, Braun RE. Hormonal regulation of spermatogenesis. Int J Androl. 2004;27(6):335–42.CrossRef Holdcraft RW, Braun RE. Hormonal regulation of spermatogenesis. Int J Androl. 2004;27(6):335–42.CrossRef
34.
go back to reference Manfo FPT, Jubendradass R, Nantia EA, Moundipa PF, Mathur PP. Adverse effects of bisphenol A on male reproductive function. In: Rev Environ Cont Toxicol Vol 228. edn: Springer; 2014. p. 57–82. Manfo FPT, Jubendradass R, Nantia EA, Moundipa PF, Mathur PP. Adverse effects of bisphenol A on male reproductive function. In: Rev Environ Cont Toxicol Vol 228. edn: Springer; 2014. p. 57–82.
35.
go back to reference Kaur S, Saluja M, Bansal M. Bisphenol A induced oxidative stress and apoptosis in mice testes: modulation by selenium. Andrologia. 2018;50(3):e12834.CrossRef Kaur S, Saluja M, Bansal M. Bisphenol A induced oxidative stress and apoptosis in mice testes: modulation by selenium. Andrologia. 2018;50(3):e12834.CrossRef
36.
go back to reference Radák Z, Kaneko T, Tahara S, Nakamoto H, Ohno H, Sasvári M, Nyakas C, Goto S. The effect of exercise training on oxidative damage of lipids, proteins, and DNA in rat skeletal muscle: evidence for beneficial outcomes. Free Radic Biol Med. 1999;27(1):69–74.CrossRef Radák Z, Kaneko T, Tahara S, Nakamoto H, Ohno H, Sasvári M, Nyakas C, Goto S. The effect of exercise training on oxidative damage of lipids, proteins, and DNA in rat skeletal muscle: evidence for beneficial outcomes. Free Radic Biol Med. 1999;27(1):69–74.CrossRef
37.
go back to reference Maćczak A, Cyrkler M, Bukowska B, Michałowicz J. Bisphenol A, bisphenol S, bisphenol F and bisphenol AF induce different oxidative stress and damage in human red blood cells (in vitro study). Toxicol in Vitro. 2017;41:143–9.CrossRef Maćczak A, Cyrkler M, Bukowska B, Michałowicz J. Bisphenol A, bisphenol S, bisphenol F and bisphenol AF induce different oxidative stress and damage in human red blood cells (in vitro study). Toxicol in Vitro. 2017;41:143–9.CrossRef
38.
go back to reference Usman A, Ahmad M. From BPA to its analogues: is it a safe journey? Chemosphere. 2016;158:131–42.CrossRef Usman A, Ahmad M. From BPA to its analogues: is it a safe journey? Chemosphere. 2016;158:131–42.CrossRef
39.
go back to reference Michałowicz J, Mokra K, Bąk A. Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study). Toxicol in Vitro. 2015;29(7):1464–72.CrossRef Michałowicz J, Mokra K, Bąk A. Bisphenol A and its analogs induce morphological and biochemical alterations in human peripheral blood mononuclear cells (in vitro study). Toxicol in Vitro. 2015;29(7):1464–72.CrossRef
40.
go back to reference Sanocka D, Kurpisz M. Reactive oxygen species and sperm cells. Reprod Biol Endocrinol. 2004;2(1):12.CrossRef Sanocka D, Kurpisz M. Reactive oxygen species and sperm cells. Reprod Biol Endocrinol. 2004;2(1):12.CrossRef
Metadata
Title
Effect of bisphenol F, an analog of bisphenol A, on the reproductive functions of male rats
Authors
Asad Ullah
Madeeha Pirzada
Tayyaba Afsar
Suhail Razak
Ali Almajwal
Sarwat Jahan
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Testosterone
Published in
Environmental Health and Preventive Medicine / Issue 1/2019
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI
https://doi.org/10.1186/s12199-019-0797-5

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