COenzyme Q10 ameliorates bisphinol A induced reproductive male toxicity: A transmission electron microscopic and immunohistochemistry study

Background and aim The endocrine disruptor compound bisphenol A (BPA) affects spermatogenesis and exacerbates benign prostate hyperplasia induced by testosterone. Nonetheless, the direct effect of BPA on prostate and testicular cells is not fully investigated. The objective of this study was to evaluate the pathogenic effects of BPA on the structure of the prostate and the ultrastructure of the testis of adult male albino rats via immunohistochemical and transmission electron microscopic study and the potential protective effect of CoQ10 supplementation. Methods A total of 30 male albino Wistar rats were categorized into five equal cohorts: group I, no treatment; group II was administered corn oil; group III received coenzyme Q10 (CoQ10); group IV was administrated BPA; and group V received BPA+CoQ10. Results BPA administration significantly decreased the mean values of the plasma fertility hormones and serum antioxidant enzymes and increased malondialdehyde. BPA administration markedly affected seminal parameters. Coadministered CoQ10 significantly reversed these biochemical changes. BPA induced histopathological alterations in the epithelium and connective tissue of prostate. Immunohistochemistry of the prostate revealed decreased E-cadherin and increased vimentin expressions in BPA-treated group. Ultrastructural analysis of the testis showed impairment of the basal lamina of seminiferous tubules and tight junctions between Sertoli cells after BPA exposure. Conclusion The biochemical and histopathological results of this study revealed direct evidence for BPA-induced male reproductive toxicity in the testes and prostate, causing male infertility. CoQ10 coadministration with BPA partially protects against its damaging effect mediated via its antioxidant capabilities.

[1]  M. El-sayed,et al.  The Toxic Effect of Bisphenol A on Albino Rat Testicles and the Possible Protective Value of Vitamin E and Melatonin , 2021, Egyptian Society of Clinical Toxicology Journal.

[2]  N. Sarg,et al.  Protective effect of indole 3 carbinol on toxicity of prenatal exposure of bisphenol A on adult rat prostate" A Light and Electron Microscopic Study" , 2021, Benha Medical Journal.

[3]  A. Hussein,et al.  The Possible Protective Effect of Melatonin and Coenzyme Q10 on Lung Injury Induced by Bleomycin in Adult Male Albino Rats , 2021 .

[4]  P. Checchi,et al.  Counteracting Environmental Chemicals with Coenzyme Q10: An Educational Primer for Use with “Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline” , 2020, Genetics.

[5]  A. A. Abdel Moneim,et al.  Impact of Coenzyme Q10 Administration on Lead Acetate-Induced Testicular Damage in Rats , 2020, Oxidative medicine and cellular longevity.

[6]  A. Kamel,et al.  Reproductive Toxicity Induced by Low Dose Bisphenol A(BPA) in Male Rats , 2020, Journal of Scientific Research in Science.

[7]  Md. Saidur Rahman,et al.  Bisphenol A affects the maturation and fertilization competence of spermatozoa. , 2020, Ecotoxicology and environmental safety.

[8]  R. Ramasamy,et al.  Decline in Serum Testosterone Levels Among Adolescent and Young Adult Men in the USA. , 2020, European urology focus.

[9]  C. Foresta,et al.  Protective Action of Eruca sativa Leaves Aqueous Extracts Against Bisphenol A-Caused In Vivo Testicular Damages. , 2019, Journal of Medicinal Food.

[10]  K. Kannan,et al.  Antioxidant CoQ10 Restores Fertility by Rescuing Bisphenol A-Induced Oxidative DNA Damage in the Caenorhabditis elegans Germline , 2019, Genetics.

[11]  K. Hayashi,et al.  Prenatal exposure to bisphenol A, E and S induces transgenerational effects on male reproductive functions in mice. , 2019, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  Md. Saidur Rahman,et al.  Understanding the molecular mechanisms of bisphenol A action in spermatozoa , 2019, Clinical and experimental reproductive medicine.

[13]  M. Yıldız,et al.  Protective effect of coenzyme Q10 against bisphenol-A-induced toxicity in the rat testes , 2019, Toxicology and industrial health.

[14]  Alabi Okunola A,et al.  Public and Environmental Health Effects of Plastic Wastes Disposal: A Review , 2019, Journal of Toxicology and Risk Assessment.

[15]  L. Khorsandi,et al.  Efficiency of naringin against reproductive toxicity and testicular damages induced by bisphenol A in rats , 2019, Iranian journal of basic medical sciences.

[16]  Asad Ullah,et al.  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. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[17]  Lorenzo Pissinatti,et al.  Cell junctions in the prostate: an overview about the effects of Endocrine Disrupting Chemicals (EDCS) in different experimental models. , 2018, Reproductive toxicology.

[18]  A. Tolba,et al.  Histological effects of bisphenol-A on the reproductive organs of the adult male albino rat , 2018 .

[19]  Jian Wu,et al.  Oral exposure of low-dose bisphenol A promotes proliferation of dorsolateral prostate and induces epithelial–mesenchymal transition in aged rats , 2018, Scientific Reports.

[20]  N. Kamimura,et al.  Phthalates impact human health: Epidemiological evidences and plausible mechanism of action. , 2017, Journal of hazardous materials.

[21]  S. Wołczyński,et al.  Endocrine-disrupting chemicals—Mechanisms of action on male reproductive system , 2017, Toxicology and industrial health.

[22]  Yan Zhao,et al.  In utero and lactational exposure to di(2-ethylhexyl) phthalate increased the susceptibility of prostate carcinogenesis in male offspring. , 2017, Reproductive toxicology.

[23]  F. Bruyère,et al.  Clinical significance of epithelial-mesenchymal transition markers in prostate cancer. , 2017, Human pathology.

[24]  N. Barlas,et al.  The toxicological effects of bisphenol A and octylphenol on the reproductive system of prepubertal male rats , 2017, Toxicology and industrial health.

[25]  M. Dixit,et al.  Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66shc-dependent antioxidant responses , 2017, Apoptosis.

[26]  Shuhua Yang,et al.  The Protective Effect of Selenium on Chronic Zearalenone-Induced Reproductive System Damage in Male Mice , 2016, Molecules.

[27]  S. M. B. Khojasteh,et al.  Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats , 2016 .

[28]  Lloyd H. Michael,et al.  The Guide for the Care and Use of Laboratory Animals. , 2016, ILAR journal.

[29]  L. F. Barbisan,et al.  Genistein reduces the noxious effects of in utero bisphenol A exposure on the rat prostate gland at weaning and in adulthood. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[30]  M. Mondal,et al.  Evaluation of subacute bisphenol – A toxicity on male reproductive system , 2015, Veterinary world.

[31]  J. Lukáčová,et al.  Dose- and time-dependent effects of bisphenol A on bovine spermatozoa in vitro , 2015, Journal of environmental science and health. Part A, Toxic/hazardous substances & environmental engineering.

[32]  W. M. Abdel-Wahab,et al.  Thymoquinone attenuates toxicity and oxidative stress induced by bisphenol A in liver of male rats. , 2014, Pakistan journal of biological sciences : PJBS.

[33]  Yi Liu,et al.  [Expressions of E-cadherin and N-cadherin in prostate cancer and their implications]. , 2014, Zhonghua nan ke xue = National journal of andrology.

[34]  Ariana Znaor,et al.  International variations and trends in testicular cancer incidence and mortality. , 2014, European urology.

[35]  M. Morsy,et al.  Protective mechanisms of coenzyme-Q10 may involve up-regulation of testicular P-glycoprotein in doxorubicin-induced toxicity. , 2014, Environmental toxicology and pharmacology.

[36]  Srijit Das,et al.  Detrimental effects of bisphenol A on development and functions of the male reproductive system in experimental rats , 2014, EXCLI journal.

[37]  W. Dekant,et al.  Endocrine effects of chemicals: aspects of hazard identification and human health risk assessment. , 2013, Toxicology letters.

[38]  Dinesh Tiwari,et al.  Mutagenic effect of Bisphenol A on adult rat male germ cells and their fertility. , 2013, Reproductive toxicology.

[39]  F. Brucker-Davis,et al.  Bisphenol A: an endocrine and metabolic disruptor. , 2013, Annales d'endocrinologie.

[40]  K. Balasubramanian,et al.  Effect of bisphenol-A on insulin signal transduction and glucose oxidation in skeletal muscle of adult male albino rat , 2013, Human & experimental toxicology.

[41]  M. Abdollahi,et al.  Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles. , 2013, Toxicology and applied pharmacology.

[42]  Ling Chen,et al.  Low dose bisphenol A impairs spermatogenesis by suppressing reproductive hormone production and promoting germ cell apoptosis in adult rats , 2012, Journal of biomedical research.

[43]  A. H. Hassan,et al.  Effects of Pre-and Postnatal Exposure to Bisphenol- A on the Reproductive Efficacy in Male Albino Rats , 2013 .

[44]  M. El-Gerbed Histopathological and ultrastructural effects of methyl parathion on rat testis and protection by selenium , 2013, Journal of Applied Pharmaceutical Science.

[45]  Wei Wu,et al.  Bisphenol A Alters n-6 Fatty Acid Composition and Decreases Antioxidant Enzyme Levels in Rat Testes: A LC-QTOF-Based Metabolomics Study , 2012, PloS one.

[46]  B. Akingbemi,et al.  The Industrial Chemical Bisphenol A (BPA) Interferes with Proliferative Activity and Development of Steroidogenic Capacity in Rat Leydig Cells1 , 2012, Biology of reproduction.

[47]  D. Kolankaya,et al.  Vitamin C coadministration augments bisphenol A, nonylphenol, and octylphenol induced oxidative damage on kidney of rats , 2011, Environmental toxicology.

[48]  J. Giesy,et al.  Effect of perinatal and postnatal bisphenol A exposure to the regulatory circuits at the hypothalamus-pituitary-gonadal axis of CD-1 mice. , 2011, Reproductive toxicology.

[49]  G. Vanage,et al.  Perinatal exposure of rats to Bisphenol A affects fertility of male offspring--an overview. , 2011, Reproductive toxicology.

[50]  A. Fouad,et al.  Coenzyme Q10 counteracts testicular injury induced by sodium arsenite in rats. , 2011, European journal of pharmacology.

[51]  C. Casals-Casas,et al.  Endocrine disruptors: from endocrine to metabolic disruption. , 2011, Annual review of physiology.

[52]  D. H. Ramdhan,et al.  Bisphenol A may cause testosterone reduction by adversely affecting both testis and pituitary systems similar to estradiol. , 2010, Toxicology letters.

[53]  Hyung Gyun Kim,et al.  Bisphenol A-induced aromatase activation is mediated by cyclooxygenase-2 up-regulation in rat testicular Leydig cells. , 2010, Toxicology letters.

[54]  V. Hancı,et al.  Coenzyme Q10 treatment reduces lipid peroxidation, inducible and endothelial nitric oxide synthases, and germ cell-specific apoptosis in a rat model of testicular ischemia/reperfusion injury. , 2010, Fertility and sterility.

[55]  T. Fujita,et al.  RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease. , 2009, Arthritis and rheumatism.

[56]  Yuan-Jie Li,et al.  Bisphenol A exposure induces apoptosis and upregulation of Fas/FasL and caspase-3 expression in the testes of mice. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[57]  H. Kubo,et al.  Food content of ubiquinol-10 and ubiquinone-10 in the Japanese diet , 2008 .

[58]  R. Cortvrindt,et al.  Continuous exposure to bisphenol A during in vitro follicular development induces meiotic abnormalities. , 2008, Mutation research.

[59]  Antonia M. Calafat,et al.  Exposure of the U.S. Population to Bisphenol A and 4-tertiary-Octylphenol: 2003–2004 , 2007, Environmental health perspectives.

[60]  A. Chauhan,et al.  Suppression of fertility in male albino rats following the administration of 50% ethanolic extract of Aegle marmelos. , 2007, Contraception.

[61]  Laura N. Vandenberg,et al.  Human exposure to bisphenol A (BPA). , 2007, Reproductive toxicology.

[62]  S. Rhee,et al.  Inhibitory effect of Bisphenol A on gap junctional intercellular communication in an epithelial cell line of rat mammary tissue , 2007, Archives of pharmacal research.

[63]  W. Jin,et al.  Adverse effects of environmental toxicants, octylphenol and bisphenol A, on male reproductive functions in pubertal rats , 2004, Endocrine.

[64]  Frederick S vom Saal,et al.  Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. , 2006, Endocrinology.

[65]  Y. Katayama,et al.  Biodegradation or metabolism of bisphenol A: from microorganisms to mammals. , 2006, Toxicology.

[66]  Paloma Alonso-Magdalena,et al.  The Estrogenic Effect of Bisphenol A Disrupts Pancreatic β-Cell Function In Vivo and Induces Insulin Resistance , 2005, Environmental health perspectives.

[67]  O. Cinar,et al.  Bisphenol-A induces cell cycle delay and alters centrosome and spindle microtubular organization in oocytes during meiosis. , 2005, Molecular human reproduction.

[68]  C. Hughes,et al.  An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment , 2005, Environmental health perspectives.

[69]  Samuel P. Caudill,et al.  Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population , 2004, Environmental health perspectives.

[70]  K. Toshimori,et al.  Adverse effects of bisphenol A to spermiogenesis in mice and rats. , 2004, Archives of histology and cytology.

[71]  M. Hardy,et al.  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. , 2004, Endocrinology.

[72]  S. Oishi,et al.  Testicular toxicity of dietarily or parenterally administered bisphenol A in rats and mice. , 2003, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[73]  Alberto Mantovani,et al.  Hazard identification and risk assessment of endocrine disrupting chemicals with regard to developmental effects. , 2002, Toxicology.

[74]  A. R. Abd-Allah,et al.  Testicular toxicity effects of magnetic field exposure and prophylactic role of coenzyme Q10 and L-carnitine in mice. , 2002, Pharmacological research.

[75]  F. L. Crane,et al.  Biochemical Functions of Coenzyme Q10 , 2001, Journal of the American College of Nutrition.

[76]  G. Koraćević,et al.  Method for the measurement of antioxidant activity in human fluids , 2001, Journal of clinical pathology.

[77]  S. Oishi,et al.  Testicular toxicity of dietary 2,2-bis(4-hydroxyphenyl)propane (bisphenol A) in F344 rats , 2001, Archives of Toxicology.

[78]  C. Martínez-García,et al.  Apoptosis precedes detachment of germ cells from the seminiferous epithelium after hormone suppression by short-term oestradiol treatment of rats. , 2002, International journal of andrology.

[79]  M. Nishikawa,et al.  Coenzyme Q10 , 2019, Pharmacy Today.