Abstract
Improper iodine intake is a major concern in public health. Chronic intake of low iodine affects gonadal functions of man and animals; however, such effects of excess iodine in male reproduction, specially on testicular morphology, testicular steroidogenic enzyme activities, sperm morphology, sperm viability, and sperm count including male hormonal profiles in reference to iodine status and thyroid hormone profiles are yet to be explored. With this background, adult male rats of 120 ± 10 gm Bw of 90 ± 5 days were divided broadly in two groups depending on the duration of the treatment for 30 and 60 days, respectively. Both the groups consisted of control animals. Excess iodine (100EI), i.e., 100 times more than its recommended level but within its tolerable ranges, was administered through gavage regularly to the first group of experimental animals for 30 and 60 days, respectively, and excessive iodine (500EI), i.e., 500 times more than its recommended level and above tolerable range in the same way and for the same durations, was administered to the other group of experimental animals. Overall results revealed that regular consumption of iodine in excess impairs reproductive functions in adult male rats depending on the dose and duration of its exposure through different mechanisms. Excess iodine accumulates in the testis which results in generation of reactive oxygen species (ROS) as evidenced by higher lipid peroxidation level as well as an imbalance in the pro-/antioxidant status inhibiting the activity of ∆5 3β- hydroxysteroid dehydrogenase (HSD) and 17β-HSD resulting to reduced synthesis of testosterone that causes structural and functional changes of the testis. Secondly, persistent generation of ROS in testis as a result of prolonged excess iodine exposure affects hypothalamo–pituitary–adrenal axis that stimulates synthesis and secretion of corticosterone which inhibits LH release that downregulates testosterone synthesis causing further testicular disruption. Thirdly, excess iodine when administered above its tolerable ranges for prolonged duration acts on thyroid itself developing a state of biochemical hypothyroidism (as evident by low T3) which further potentiate the disrupting effect of excess iodine on male gonads by reducing circulating testosterone level.
Similar content being viewed by others
References
Alsayed A, Gad AM, Abdel-Baset H, Abdel-Fattah A, Ahmed A, Azab A (2008) Excess urinary iodine is associated with autoimmune subclinical hypothyroidism among Egyptian women. Endocr J 55(3):601–605
Camargo RY, Tomimori EK, Neves SC, Rubio GSI, Galrão AL, Knobel M, Medeiros-Neto G (2008) Thyroid and the environment: exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in Sao Paulo, Brazil. Eur J Endocrinol 159(3):293–299
Seal AJ, Creeke PI, Gnat D, Abdalla F, Mirghani Z (2006) Excess dietary iodine intake in long-term African refugees. Public Health Nutr 9(1):35–39
Zhao LN, Xu J, Peng XL, Tian LY, Hao LP, Yang XF, Ying CJ, Sun XF (2010) Dose and time dependent hypercholesterolemia effects of iodine excess via TRβ1-mediated down regulation of hepatic LDLr gene expression. Eur J Nutr 49(5):257–265
Paulíková I, Kováč G, Bíreš J, Paulík S, Seidel H, Nagy O (2002) Iodine toxicity in ruminants. Vet Med Czech 47(12):343–350
Han H, Xin P, Zhao L, Xu J, Xia Y, Yang X, Sun X, Hao L (2012) Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice. Biol Trace Elem Res 147:233–239
Wagner MS, Wajner SM, Maia AL (2008) The role of thyroid hormone in testicular development and function. J Endocrinol 199(3):351–365
Joanta AE, Filip A, Clichici S, Andrei S, Daicoviciu D (2006) Iodine exerts oxidative stress in some target tissues of the thyroid hormones. Acta Physiol Hung 93(4):347–359
Pereira A, Braekman JC, Dumont JE, Boeynaems JM (1990) Identification of a major iodolipid from the horse thyroid gland as 2-iodohexadecanal. J Biol Chem 265(28):17018–17025
Griveau JF, Dumont E, Renard P, Callegari JP, Le Lannou D (1995) Reactive oxygen species, lipid peroxidation and enzymatic defense systems in human spermatozoa. J Reprod Fertil 103(1):17–26
Agarwal A, Gupta S, Sikka S (2006) The role of free radicals and antioxidants in reproduction. Curr Opin Obstet Gynecol 18:325–332
Aitken RJ, Baker MA (2006) Oxidative stress, sperm survival and fertility control. Mol Cell Endocrinol 250:66–69
Kao SH, Chao HT, Chen HW, Hwang TI, Liao TL, Wei YH (2008) Increase of oxidative stress in human sperm with lower motility. FertilSteril 89(5):1183–1190
deLamirande E, Gagnon C (1995) Impact of reactive oxygen species on spermatozoa: A balancing act between beneficial and detrimental effects. Hum Reprod 10:15–21
Turner TT, Lysiak JJ (2008) Oxidative stress: a common factor in testicular dysfunction. J Androl 29(5):488–498
Shoyinka SVO, Obidike IR, Ndumnego CO (2008) Effect of iodine supplementation on thyroid and testicular morphology and function in euthyroid rats. Vet Res Commun 32(8):635–645
Chandra AK, Ghosh R, Chatterjee A, Sarkar M (2007) Amelioration of vanadium-induced testicular toxicity and adrenocortical hyperactivity by vitamin E acetate in rats. Moll Cell Biochem 306:189–200
Lupachik SV, Nadol’nik LI, Netsetskaya ZV, Vinogradov VV (2007) Effect of long-term injection of high doses of potassium iodide on iodine metabolism in rat thyroid gland. Biomed Chem 1(1):53–57
Burgi H (2010) Iodine excess. Best Pract Res Clin Endocrinol Metab 24(1):107–115
Leblond PC, Clermont Y (1952) Definition of the stages of the seminiferous epithelium in the rat. Ann N Y Acad Sci 55(4):548–573
Mortimer D (1994) Practical laboratory andrology. Oxford University Press, New York, pp 66–69
Talalay P (1962) Hydroxy steroid dehydrogenase. In: Colowick SP (ed) Methods in enzymology, 5th edn. Academic, New York, pp 513–532
Jarabak J, Adams JA, Williams-Ashman HG, Talalay P (1962) Purification of a17β hydroxysteroid dehydrogenase of human placenta and studies on its trans-hydrogenase function. J Biol Chem 237:345–357
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Paoletti F, Mocali A (1990) Determination of superoxide dismutase activity by purely chemical system based on NAD (P) H oxidation. Methods Enzymol 186:209–220
Aebi H. (1974) Catalase. In: Bergmeyer HU (ed) Methods in enzymatic analysis, 2nd edn. Academic, New York, pp 673–678
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590
Karmarkar MG, Pandav CS, Krishnamachari KA (1986) Principle and procedure for iodine estimation. In: A laboratory manual. Indian Council of Medical Research, New Delhi, pp 1–14
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement from phenol reagent. J Biol Chem 193(1):265–275
Dunn JT, Crutchfield HE, Gutekunst R, Dunn AD (1993) Methods for measuring iodine in urine (ICCIDD/UNICEF/WHO). World Health Organization, The Netherlands, pp 18–27
Chandra AK, Mondal C, Sinha S, Chakraborty A, Pearce EN (2015) Synergic actions of polyphenols and cyanogens of peanut seed coat (Arachis hypogaea) on cytological, biochemical and functional changes in thyroid. Indian J Exp Biol 53(3):143–151
Chandra AK, Mukhopadhyay S, Ghosh D, Tripathy S (2006) Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats. Indian J Exp Biol 44(8):653–661
Spitzweg C, Morris JC (2002) The sodium iodide symporter: its pathophysiological and therapeutic implications. Clin Endocrinol (Oxf) 57(5):559–574
Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG (2001) Iodine-induced hypothyroidism. Thyroid 11(5):501–509
Leung K, Conwey EM, Conner GH (1980) Effect of dietary iodide on hypophyseal and thyroid hormone secretions in Holstein-Friesian heifers. Am J Vet Res 41:1402–1407
Yang XF, Xu J, Hou XH, Guo HL, Hao LP, Yao P, Liu LG, Sun XF (2006) Developmental toxic effects of chronic exposure to high doses of iodine in the mouse. Repro Toxicol 22:725–730
Schone F, Zimmermann C, Quanz G, Richter G, Leiterer M (2006) A high dietary iodine increases thyroid iodine stores and iodine concentration in blood serum but has little effect on muscle iodine content in pigs. Meat Sci 72:365–372
Lewis PD (2004) Responses of domestic fowl to excess iodine: A review. Br J Nutr 91:29–39
Chakraborty A, Mondal C, Sinha S, Mandal J, Chandra AK (2014) Amiodarone induced oxidative stress in stress-vulnerable organs of adult male rats. Asian J Pharm Clin Res 7(4):177–183
Chandra AK, Ghosh R, Chatterjee A, Sarkar M (2007) Effects of vanadate on male rat reproductive tract histology, oxidative stress markers and androgenic enzyme activities. J Inorg Biochem 101:944–956
Yang XF, Xu J, Hou XH, Hao LP, Liu LG, Sun XF (2007) Effect of excessive iodine exposure on the placental deiodinase activities and Hoxc8 expression during mouse embryogenesis. Br J Nutr 98:116–122
Roti E, Minelli R, Gardint E, Bianconi L, Neri T, Gavaruzzi G, Ugolotti G, Salvo D, Braverman LE (1991) Impaired intrathyroidal iodine organification and iodine-induced hypothyroidism in euthyroid women with a previous episode of postpartum thyroiditis. J Clin Endocrinol Metab 73:958–963
Chow CC, Phillips DI, Lazarus JH, Parkes AB (1991) Effect of low dose iodide supplementation on thyroid function in potentially susceptible subjects: Are dietary iodide levels in Britain acceptable? Clin Endocrinol (Oxf) 34(5):413–416
Cavaliere H, Abelin N, Medeiros-neto G (1988) Serum levels of total testosterone and sex hormone binding globulin in hypothyroid patients and normal subjects treated with incremental doses of L-T4 or L-T3. J Androl 9(3):215–219
Maneesh M, Dutta S, Chakrabarti A, Vasudevan DM (2006) Alcohol abuse-duration dependent decrease in plasma testosterone and antioxidants in males. Indian J Physiol Pharmacol 50(3):291–296
Russo D, Scipioni A, Durante C, Ferretti E, Gandini L, Maggisano V, Paoli D, Verrienti A, Costante G, Lenzi A, Filetti S (2011) Expression and localization of the sodium/iodide symporter (NIS) in testicular cells. Endocrine 40:35–40
Vitale M, Di Matola T, D’Ascoli F, Salzano S, Bogazzi F, Fenzi G, Martino E, Rossi G (2000) Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. Endocrinology 141(2):598–605
Mates JM, Perez-Gomez C, De Castro IN (1999) Antioxidant enzymes and human diseases. Clin Biochem 32(8):595–603
Chandra AK, Sinha S, Choudhury SR (2010) Thyroxine induced stress and its possible prevention by catechin. Indian J Exp Biol 48:559–565
Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of Se-glutathione peroxidase, catalase, and CU/ZN-SOD for cell survival against oxidative stress. Free Radic Biol Med 17(3):235–248
Clermont Y, Morgentaler H (1955) Quantitative study of spermatogenesis in hypophysectomized rats. Endocrinology 57:369–382
Chandra AK, Ghosh R, Chatterjee A, Sarkar M (2010) Protection against vanadium-induced testicular toxicity by testosterone propionate in rats. Toxicol Mech Meth 20(6):306–315
Sakr SA, Zoil M-S, El-Shafey SS (2013) Ameliorative effect of grapefruit juice on amiodarone-induced cytogenetic and testicular damage in albino rats. Asian Pac J Trop Biomed 3(7):573–579
Björndahl L, Söderlund I, Kvist U (2003) Evaluation of the one-step eosin-nigrosin staining technique for human sperm vitality assessment. Hum Reprod 18(4):813–816
Viau V (2002) Functional cross talk between hypothalamic-pituitary-gonadal and adrenal axes. J Neuroendocrinol 14:506–513
Chandra AK, Chatterjee A, Ghosh R, Sarkar M (2007) Chromium induced testicular impairment in relation to adrenocortical activities in adult albino rats. Reprod Toxicol 24:388–396
Rivier C, Rivest S (1991) Effect of stress on the activity of the hypothalamic pituitary-gonadal axis: peripheral and central mechanisms. Biol Reprod 45:523–532
Tilbrook AJ, Turner AI, Clarke IJ (2000) Effects of stress on reproduction in non-rodent mammals: the role of glucocorticoids and sex differences. Rev Reprod 5:105–113
Acknowledgments
The authors are thankful to Prof. T. G. Srivastava, National Institute for Health and Family Welfare (NIHFW)—Govt. of India, New Delhi, India for his generous help in providing corticosterone kits. The authors are grateful to Prof. Arun K. Ray, Fellow, Alexander von Humboldt Foundation, Germany and Ex-Senior Professor and Emeritus Scientist (CSIR), Division of Molecular Medicine, Bose Institute, Calcutta for the review and language improvement of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
The entire work was financially supported by Major Research Project under University Grants Commission (UGC), New Delhi, Govt. of India [Sanction No.41-84/2012(SR) dated 11th July 2012].
Conflict of Interest
The authors declared no potential conflicts of interest with respect to the authorship, research, or publication of this article.
Rights and permissions
About this article
Cite this article
Chakraborty, A., Mandal, J., Mondal, C. et al. Effect of Excess Iodine on Oxidative Stress Markers, Steroidogenic—Enzyme Activities, Testicular Morphology, and Functions in Adult Male Rats. Biol Trace Elem Res 172, 380–394 (2016). https://doi.org/10.1007/s12011-015-0581-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-015-0581-3