DOI QR코드

DOI QR Code

Testosterone recuperates deteriorated male fertility in cypermethrin intoxicated rats

  • Katragadda, Vasudha (Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University)) ;
  • Adem, Meghapriya (Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University)) ;
  • Mohammad, Reshma Anjum (Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University)) ;
  • Bhasyam, Sainath Sri (Department of Biotechnology, Vikrama Simhapuri University) ;
  • Battini, Kishori (Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University))
  • Received : 2019.10.07
  • Accepted : 2020.03.26
  • Published : 2021.01.15

Abstract

The present study investigates the protective effects of testosterone against reproductive toxicity induced by cypermethrin (50 mg/kg body weight) in rats. Significant reduction in the testicular and accessory sex organ weights were observed in cypermethrin-treated rats over controls. Cypermethrin intoxication significantly reduced testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability and HOS-tail coiled sperm accompanied by significant reduction in the activity levels of testicular steroidogenic enzymes such as 3β- and 17β- hydroxysteroid dehydrogenases in rats as compared to controls. Further, qPCR studies indicated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR) significantly decreased in cypermethrin-treated rats over controls. Molecular docking analysis indicated that the binding affinity of cypermethrin (-11.2 kcal/mol) towards StAR protein was greater as compared to its natural ligand, cholesterol (-8.2 kcal/mol) suggesting improper cholesterol channeling across the testis. Significant reduction in the circulatory levels of testosterone was also recorded in cypermethrin-exposed rats. An increase in pre- and post-implantation loss was observed in rats cohabited with cypermethrin-treated rats. On the other hand, testosterone (4.16 mg/kg body weight) treatment ameliorated cypermethrin-induced reprotoxic effects in rats. To conclude, cypermethrin-induced deterioration of suppressed reproductive performance in male rats could be linked to its antiandrogenic effects and on the other hand, testosterone-mediated protection of male reproductive health in cypermethrin-treated rats at least in part occurs via restoration of testosterone biosynthesis, spermatogenesis and sperm maturation events.

Keywords

Acknowledgement

The authors are thankful to Head, Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam, Tirupati for providing laboratory facilities. Authors also thankful to DST-CURIE, Central Instrumentation Facility, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati, for permitting to utilize equipments.

References

  1. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE (1992) Evidence for decreasing quality of semen during past 50 years. BMJ 305:609-613 https://doi.org/10.1136/bmj.305.6854.609
  2. Andersson AM, Jorgensen N, Main KM, Toppari J, Rajpert-De Meyts E, Leffers H, Juul A, Jensen TK, Skakkebaek NE (2008) Adverse trends in male reproductive health: we may have reached a crucial 'tipping point'. Int J Androl 31:74-80 https://doi.org/10.1111/j.1365-2605.2007.00853.x
  3. Oliva A, Spira A, Multigner L (2001) Contribution of environmental factors to the risk of male infertility. Hum Reprod 16:1768-1776 https://doi.org/10.1093/humrep/16.8.1768
  4. Swan SH, Kruse RL, Liu F, Dana Barr B, Erma Drobnis Z, Bruce Redmon J, Wang C, Brazil C, James Overstreet W (2003) Semen quality in relation to biomarkers of pesticide exposure. Environ Health Perspect 111:1478-1484 https://doi.org/10.1289/ehp.6417
  5. Lifeng T, Shoulin W, Junmin J, Xuezhao S, Yannan L, Qianli W, Longsheng C (2006) Effects of fenvalerate exposure on semen quality among occupational workers. Contraception 73:92-96 https://doi.org/10.1016/j.contraception.2005.06.067
  6. Erstfeld KM (1999) Environmental fate of synthetic pyrethroids during spray drifts and field runoff treatments in aquatic microcosms. Chemosphere 39:1737-1769 https://doi.org/10.1016/S0045-6535(99)00064-8
  7. Assayed M, Salem H, Khalaf A (2008) Protective effects of garlic extract and vitamin C against Cypermethrin reproductive toxicity in male rats. Res J Veter Sci 1:1-5
  8. Kaufman DD, Beverly AR, Charles SH, Anthony JK (1981) Movement of cypermethrin, decamethrin, permethrin, and their degradation products in soil. J Agric Food Chem 29:239-245 https://doi.org/10.1021/jf00104a008
  9. U.S.D.A. (United States Department of Agriculture), Agricultural Research Service (1995) ARS Pesticide Properties: wizad.arsuds.gov/rsml/textfiles/cypermethrin
  10. Sharma P, Khan IA, Singh R (2018) Curcumin and quercetin ameliorated cypermethrin and deltamethrin-induced reproductive system impairment in male wistar rats by upregulating the activity of pituitary-gonadal hormones and steroidogenic enzymes. Int J Fertil Steril 12:72-80 https://doi.org/10.22074/ijfs.2018.5160
  11. Kjeldsen LS, Ghisari M, Bonefeld-Jorgensen EC (2013) Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity. Toxicol Appl Pharmacol 272:453-464 https://doi.org/10.1016/j.taap.2013.06.028
  12. Hu JX, Li YF, Li J, Pan C, He Z, Dong HY, Xu LC (2013) Toxic effects of cypermethrin on the male reproductive system: with emphasis on the androgen receptor. J Appl Toxicol 33:576-585 https://doi.org/10.1002/jat.1769
  13. Wang XZ, Liu SS, Sun Y, Wu JY, Zhou YL, Zhang JH (2009) Beta-cypermethrin impairs reproductive function in male mice by inducing oxidative stress. Theriogenology 72:599-611 https://doi.org/10.1016/j.theriogenology.2009.04.016
  14. Yousef MI, el-Demerdash FM, Kamel KI, Al-Salhen KS (2003) Changes in some hematological and biochemical indices of rabbits induced by isoflavones and cypermethrin. Toxicology 189:223-234 https://doi.org/10.1016/S0300-483X(03)00145-8
  15. Wang H, Wang Q, Zhao XF, Liu P (2010) Cypermethrin exposure during puberty disrupts testosterone synthesis via down regulation StAR in mouse testes. Arch Toxicol 84:53-61 https://doi.org/10.1007/s00204-009-0479-y
  16. Solati J, Hajikhani R, Zaeim RT (2010) Effects of cypermethrin on sexual behaviour and plasma concentrations of pituitary-gonadal hormones. Int J Fertil Steril 4:23-28
  17. Hashem HE, Abd El-Haleem MR, Abass MA (2015) Epithelial and stromal alterations in prostate after cypermethrin administration in adult albino rats (histological and biochemical study). Tissue Cell 47:366-372 https://doi.org/10.1016/j.tice.2015.04.007
  18. Sahar MES, Lobna SEG, Maha RBE, Nabila IES (2016) Toxic effects of cypermethrin on male fertility and some hepatic biochemical parameters in male albino rats. Egypt J Chem Environ Health 2:66-77 https://doi.org/10.21608/ejceh.2016.246181
  19. Li YF, Pan C, Hu JX, Li J, Xu LC (2013) Effects of cypermethrin on male reproductive system in adult rats. Biomed Environ Sci 26:201-208 https://doi.org/10.3967/0895-3988.2013.03.007
  20. Vasudha K, Meghapriya A, Kishori B (2018) Recovery of male reproductive health in cypermethrin exposed rats by testosterone. Int J Res Anal Rev 5:311-317
  21. Travison TG, Shackelton R, Araujo AB, Hall SA, Williams RE, Clark RV, O'Donnell AB, McKinlay JB (2008) The natural history of symptomic androgen deficiency in men: onset, progression, and spontaneous remission. J Am Geriatric Soc 56:831-839 https://doi.org/10.1111/j.1532-5415.2008.01679.x
  22. C.P.C.S.E.A. (2003) Guidelines for laboratory animal facility. Indian J Pharmacol 35:257-274
  23. Blazak WF, Treinen KA, Juniewicz PE (1993) Application of testicular sperm head counts in the assessment of male reproductive toxicity. Met Toxicol 3:86-94
  24. Robb GW, Amann RP, Killian GJ (1978) Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J Reprod Fertil 54:103-107 https://doi.org/10.1530/jrf.0.0540103
  25. Belsey MA, Moghissi KA, Eliasson R, Paulsen CA, Callegos AJ, Prasad MRN (1980) Laboratory manual for the examination of human semen and semen cervical mucus interaction. Press Concern, Singapore
  26. Talbot P, Chacon RS (1981) A triple stain technique for evaluating normal acrosome reaction of human sperm. J Exp Zool 215:201-208 https://doi.org/10.1002/jez.1402150210
  27. Jeyendran RS, Vander HH, Ven Zaneveld LID (1992) The hypo-osmotic swelling test: an update. Arch Androl 29:105-116 https://doi.org/10.3109/01485019208987714
  28. Bergmayer HU (1974) Methods of enzymatic analysis. Verlag Chemie/Academic Press, Weinheim/New York, pp 447-489
  29. Joshi SC, Bansal B, Jasuja ND (2011) Evaluation of reproductive and developmental toxicity of Cypermethrin in male albino rats. Toxicol Environ Chem 93:593-602 https://doi.org/10.1080/02772248.2010.537441
  30. Sanhez LC, Reyes BE, Labez Carrill OL (2004) Organophosphorous pesticides exposure alters sperm chromatin structure in Mexican agricultural workers. Toxicol Appl Pharmacol 94:108-113
  31. Giribabu N, Sreenivasula Reddy P (2017) Protection of male reproductive toxicity in rats exposed to di-n-butyl phthalate during embryonic development by testosterone. Biomed Pharmacother 87:355-365 https://doi.org/10.1016/j.biopha.2016.12.106
  32. Reshma AM, Sreenivasula Reddy P (2014) Recovery of lead-induced suppressed reproduction in male rats by testosterone. Andrologia 47:560-567 https://doi.org/10.1111/and.12303
  33. Nordberg FG (1975) Effects of long-term cadmium exposure on the seminal vesicles of mice. Reprod Fertil 45:165-167 https://doi.org/10.1530/jrf.0.0450165
  34. Sharma P, Huq AU, Singh R (2014) Cypermethrin-induced reproductive toxicity in the rat is prevented by resveratrol. J Hum Reprod Sci 7:99-106 https://doi.org/10.4103/0974-1208.138867
  35. Labrie F, Simard J, Luu-The V, Belanger A, Pelletier G (1992) Structure, function and tissue-specific gene expression of 3β-hydroxysteroid dehydrogenase/5-ene-4-ene isomerase enzymes in classical and peripheral intracrine steroidogenic tissues. J Steroid Biochem Mol Biol 43:805-826 https://doi.org/10.1016/0960-0760(92)90308-6
  36. Liu P, Song XX, Wen WH, Yuan WH, Chen XM (2006) Effects of mixed cypermethrin and methylparathion on endocrine hormone levels and immune function of rat: II Interation. Wei Sheng Yan Jiu 35:531-533
  37. Zhang SY, Ito Y, Yamanoshita O, Yanagiba Y, Kobayashi M, Taya K, Li C, Okamura A, Miyata M, Ueyama J, Lee CH, Kamijima M, Nakajima T (2007) Permethrin may disrupt testosterone biosynthesis via mitochondrial membrane. Endocrinology 148:3941-3949 https://doi.org/10.1210/en.2006-1497
  38. Rangel PL, Rodriguez A, Rojas S, Sharp PJ, Gutierrez CG (2009) Testosterone stimulates progesterone production and STAR, P450 cholesterol side-chain cleavage and LH receptor mRNAs expression in hen (Gallus domesticus) granulosa cells. Reproduction 138:961-969 https://doi.org/10.1530/REP-09-0071
  39. Houk CP, Pearson EJ, Martinelle N, Donahoe PK, Teixeira J (2004) Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens. Endocrinology 145:1269-1275 https://doi.org/10.1210/en.2003-1046
  40. Bleil JD, Wassarman PM (1983) Sperm-egg interactions in the mouse: sequence of events and induction of the acrosome reaction by zona pellucida glycoprotein. Dev Biol 95:317-324 https://doi.org/10.1016/0012-1606(83)90032-5
  41. Harrison RA, Vickers SE (1990) Use of fluorescent probes to assess membrane integrity in mammalian spermatozoa. J Reprod Fertil 88:343-352 https://doi.org/10.1530/jrf.0.0880343
  42. Alaa-Eldin EA, El-Shafei DA, Abouhashem NS (2017) Individual and combined effect of chlorpyrifos and cypermethrin on reproductive system of adult male albino rats. Environ Sci Pollut Res 24:1532-1542 https://doi.org/10.1007/s11356-016-7912-6
  43. Elbetieha A, Daas SI, Khamas W, Darmani H (2001) Evaluation of the toxic potentials of cypermethrin pesticide on some reproductive and fertility parameters in the male rats. Arch Environ Contam Toxicol 41:522-528 https://doi.org/10.1007/s002440010280
  44. Kishore Reddy YV, Sreenivasula Reddy P, Shivalingam MR (2010) Testosterone mediated partial recovery of carboplatin induced reproductive toxicity in male wistar rats. J Biomed Sci Res 2:46-53

Cited by

  1. Cypermethrin triggers YY1-mediated testosterone biosynthesis suppression vol.225, 2021, https://doi.org/10.1016/j.ecoenv.2021.112792