Hostname: page-component-669899f699-cf6xr Total loading time: 0 Render date: 2025-04-27T05:07:00.525Z Has data issue: false hasContentIssue false
  • English
  • Français

Malathion exposure during juvenile and peripubertal periods downregulate androgen receptor and 17-ß-HSD testicular gene expression and compromised sperm quality in rats

Published online by Cambridge University Press:  07 November 2022

Rafaela Pires Erthal Open the ORCID record for Rafaela Pires Erthal [Opens in a new window] ,
Gláucia Eloisa Munhoz de Lion Siervo ,
Giovanna Fachetti Frigoli ,
Tiago Henrique Zaninelli ,
Waldiceu Aparecido Verri  and
Glaura Scantamburlo Alves Fernandes Open the ORCID record for Glaura Scantamburlo Alves Fernandes [Opens in a new window]
Rafaela Pires Erthal*
Affiliation:
Department of General Biology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil
Gláucia Eloisa Munhoz de Lion Siervo
Affiliation:
Department of General Biology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil
Giovanna Fachetti Frigoli
Affiliation:
Department of General Biology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil
Tiago Henrique Zaninelli
Affiliation:
Department of General Biology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil
Waldiceu Aparecido Verri
Affiliation:
Department of General Biology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil
Glaura Scantamburlo Alves Fernandes
Affiliation:
Department of General Biology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil
*
Address for correspondence: Rafaela Pires Erthal, Department of General Pathology, Biological Sciences Center, State University of Londrina – UEL, Rodovia Celso Garcia Cid, Londrina, Paraná 86057-970, Brazil. Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Malathion is an insecticide that is used to control arboviruses and agricultural pests. Adolescents that are exposed to this insecticide are the most vulnerable as they are in the critical period of postnatal sexual development. This study aimed to evaluate whether malathion damage can affect sperm function and its respective mechanisms when adolescents are exposed during postnatal sexual development. Twenty-four male Wistar rats (PND 25) were divided into three experimental groups and treated daily for 40 d: control group (saline 0.9%), 10 mg/kg (M10 group), or 50 mg/kg (M50 group) of malathion. At PND 65, the rats were anesthetized and euthanized. Testicles were collected for the evaluation of gene expression. Sperm cells from the epididymis were used for evaluation of the oxidative profile or spermatic function. Data showed that a lower dose of malathion downregulated the gene expression of androgen receptors and testosterone converter enzyme 17-β-HSD in the testis. The acrosomal integrity of sperm cells was compromised in the M50 group, but not the M10 group. The mitochondrial activity was not impaired by exposure. Finally, although no alterations in malondialdehyde and glutathione levels were observed, malathion, at both doses, increased antioxidant enzyme catalase activity and, at a higher dose, superoxide dismutase activity. The present study showed that low doses of malathion considered to be inoffensive are capable of impairing sperm quality and function through the downregulation of testicular genic expression of AR enzyme 17-β-HSD and can damage the spermatic antioxidant profile during critical periods of development.

Keywords

Spermgene expressionmalathionantioxidantspostnatal development
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 14 , Issue 2 , April 2023 , pp. 286 - 293
Check for updates
Copyright
© The Author(s), 2022. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

E P A. In: Reregistration Eligibility Decision (RED) for Malathion. EPA 738-R-06-030. U.S, Off. Prev. Pestic. Toxic Subst. Off. Pestic. Programs, 2006. U.S. Government Printing Office, Whashington, DC.Google Scholar
Nash, JP, Kime, DE, Van der Ven, LTM, et al. Long-term exposure to environmental concentrations of the pharmaceutical ethynylestradiol causes reproductive failure in fish. Environ Health Persp. 2004; 112(17), 1725–1733. DOI 10.1289/ehp.7209.CrossRefGoogle ScholarPubMed
Maroni, M, Colosio, C, Ferioli, A, Fait, A. Biological monitoring of pesticide exposure: a review. Toxicology. 2000; 7, 1–118.Google Scholar
D. O. C. O. N. T. D. WHO. Use of malathion for vector control: report of a WHO Meeting Geneva, 2016). (accessed January 3, 2018). http://apps.who.int/iris/bitstream/10665/207475/1/9789241510578_eng.pdf,Google Scholar
FAO. In: Pesticide Residues in Food: Report of the Joint Meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and the WHO Expert Group on Pesticide Residues, 1997. Food and Agriculture Organization of the United Nations.Google Scholar
Erthal, RP, Siervo, GEML, Staurengo-Ferrari, L, et al. Impairment of postnatal epididymal development and immune microenvironment following administration of low doses of malathion during juvenile and peripubertal periods of rats. Hum Exp Toxicol. 2020; 39(11), 1487–1496. DOI 10.1177/0960327120930076.CrossRefGoogle ScholarPubMed
Erthal, RP, Staurengo-Ferrari, L, Fattori, V, et al. Exposure to low doses of malathion during juvenile and peripubertal periods impairs testicular and sperm parameters in rats: role of oxidative stress and testosterone. Adv Exp Med Biol. 2020; 96, 17–26. DOI 10.1016/j.reprotox.2020.05.013.Google ScholarPubMed
Gluckman, PD, Hanson, MA, Pinal, C. The developmental origins of adult disease. Matern Child Nutr. 2005; 1(3), 130–141. DOI 10.1111/J.1740-8709.2005.00020.X.CrossRefGoogle ScholarPubMed
Hanson, MA, Gluckman, PD. Early developmental conditioning of later health and disease: physiology or pathophysiology? Physiol Rev. 2014; 94, 1027–1076. DOI 10.1152/PHYSREV.00029.2013/ASSET/IMAGES/LARGE/Z9J0041427020011.JPEG.CrossRefGoogle ScholarPubMed
Podestá, EJ, Rivarola, MA, Jyujo, T. Concentration of androgens in whole testis, seminiferous tubules and interstitial tissue of rats at different stages of development. Endocrinology. 1974; 95(2), 455–461. DOI 10.1210/endo-95-2-455.CrossRefGoogle ScholarPubMed
Benton, L, Shan, L, Hardy, M. Differentiation of adult Leydig cells. J Steroid Biochem Mol Biol. 1995; 53(1-6), 61–68. DOI 10.1016/0960-0760(95)00022-R.CrossRefGoogle ScholarPubMed
Golub, MS, Collman, GW, Foster, PMD, et al. Public Health Implications of Altered Puberty Timing. Pediatrics. 2008; 121(Supplement_3), S218–S230. DOI 10.1542/peds.2007-1813G.CrossRefGoogle ScholarPubMed
De Jonge, CJ, Barratt, C. The Sperm Cell: Production, Maturation, Fertilization, Regeneration, 2006. (Cambridge University Press.CrossRefGoogle Scholar
Stival, C, del C. Puga Molina, L, Paudel, B, Buffone, MG, Visconti, PE, Krapf, D. Sperm capacitation and acrosome reaction in mammalian sperm. Adv. Anat Embriol Cell Biol. 2016; 220, 93–106. DOI 10.1007/978-3-319-30567-7_5.CrossRefGoogle ScholarPubMed
Agarwal, A, Aitken, RJ, Alvarez, JG. Studies on Men’s Health and Fertility, 2012. Humana Press Inc, 10.1007/978-1-61779-776-7 CrossRefGoogle Scholar
Eskenazi, B, Kidd, SA, Marks, AR, Sloter, E, Block, G, Wyrobek, AJ. Antioxidant intake is associated with semen quality in healthy men. Hum Reprod. 2005; 20(4), 1006–1012. DOI 10.1093/humrep/deh725.CrossRefGoogle ScholarPubMed
Lasram, MM, Lamine, AJ, Dhouib, IB, et al. Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life Sci. 2014; 107(1-2), 50–58. DOI 10.1016/j.lfs.2014.04.033.CrossRefGoogle ScholarPubMed
Sharma, RK, Alka, G. Malathion induced changes in catalase and superoxide dismutase in testicular tissues of goat in vitro. Int J Pharm Biol Sci. 2013; 3, 193–197.Google Scholar
Guo, D, Liu, W, Yao, T, et al. Combined endocrine disruptive toxicity of malathion and cypermethrin to gene transcription and hormones of the HPG axis of male zebrafish (Danio rerio). Chemosphere. 2021; 267, 128864. DOI 10.1016/J.CHEMOSPHERE.2020.128864.CrossRefGoogle ScholarPubMed
Nohynek, GJ, Borgert, CJ, Dietrich, D, Rozman, KK. Endocrine disruption: fact or urban legend? Toxicol Lett. 2013; 223(3), 295–305. DOI 10.1016/J.TOXLET.2013.10.022.CrossRefGoogle ScholarPubMed
De Coster, S, Van Larebeke, N. Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J Environ Public Health. 2012; 2012, 1–52. DOI 10.1155/2012/713696.CrossRefGoogle ScholarPubMed
Scully, CM, Estill, CT, Amodei, R, et al. Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior. Domest Anim Endocrin. 2018; 62, 1–9. DOI 10.1016/J.DOMANIEND.2017.07.001.CrossRefGoogle ScholarPubMed
García-Vargas, D, Juárez-Rojas, L, Maya, SRojas, Retana-Márquez, S. Prenatal stress decreases sperm quality, mature follicles and fertility in rats. Syst Biol Reprod Mec. 2019; 65, 223–235. DOI 10.1080/19396368.2019.1567870/SUPPL_FILE/IAAN_A_1567870_SM5192.ZIP.CrossRefGoogle ScholarPubMed
Shi, Z, Lv, Z, Hu, C, et al. Oral exposure to Genistein during conception and lactation period affects the testicular development of male offspring mice. Animals. 2020; 10(3), 2020–2377. DOI 10.3390/ANI10030377.CrossRefGoogle ScholarPubMed
Foureman, GL, Kenyon, EM. Harmonization in Interspecies Extrapolation: Use of BW3/4 as Default Method in Derivation of the Oral RfD, 2006. USEPA.Google Scholar
Nielsen, E, Grete Ostergaard, J. Toxicological Risk Assessment of Chemicals: A Practical Guide, 2008. Larsen Informa Healthcare USA.CrossRefGoogle Scholar
Welshons, WV, Nagel, SC, Vom Saal, FS. Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology. 2006; 147(6), s56–s69. DOI 10.1210/EN.2005-1159.CrossRefGoogle ScholarPubMed
Geng, X, Shao, H, Zhang, Z, Ng, JC, Peng, C. Malathion-induced testicular toxicity is associated with spermatogenic apoptosis and alterations in testicular enzymes and hormone levels in male Wistar rats. Environ Toxicol Phar. 2015; 39(2), 659–667. DOI 10.1016/j.etap.2015.01.010.CrossRefGoogle ScholarPubMed
Ojeda, SR, Andrews, WW, Advis, JP, White, SS. Recent advances in the endocrinology of puberty. Endocr Rev. 1980; 1(3), 228–257. DOI 10.1210/edrv-1-3-228.CrossRefGoogle ScholarPubMed
Silva, EJR, Vendramini, V, Restelli, A, Bertolla, RP, Kempinas, WG, Avellar, MCW. Impact of adrenalectomy and dexamethasone treatment on testicular morphology and sperm parameters in rats: insights into the adrenal control of male reproduction. Andrology. 2014; 2(6), 835–846. DOI 10.1111/j.2047-2927.2014.00228.x.CrossRefGoogle ScholarPubMed
Bradford, MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72(1-2), 248–254. DOI 10.1016/0003-2697(76)90527-3.CrossRefGoogle ScholarPubMed
Lushchak, OV, Kubrak, OI, Lozinsky, OV, Storey, JM, Storey, KB, Lushchak, VI. Chromium(III) induces oxidative stress in goldfish liver and kidney. Aquat Toxicol. 2009; 93(1), 45–52. DOI 10.1016/J.AQUATOX.2009.03.007.CrossRefGoogle ScholarPubMed
Buege, JA, Aust, SA. Microsomal lipid peroxidation methods. Enzymol. 1978; 52, 302–310.CrossRefGoogle Scholar
Rahman, I, Kode, A, Biswas, SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc. 2007; 1(6), 3159–3165. DOI 10.1038/nprot.2006.378.CrossRefGoogle Scholar
Aebi, H. [13] Catalase in vitro. Method Enzymol. 1984; 105, 121–126. DOI 10.1016/S0076-6879(84)05016-3.CrossRefGoogle Scholar
Senthilkumar, M, Amaresan, N, Sankaranarayanan, A. Plant-Microbe Interactions, 2021. Springer US, New York, NY, 10.1007/978-1-0716-1080-0 CrossRefGoogle Scholar
Keen, JH, Habig, WH, Jakoby, WB. Mechanism for the several activities of the glutathione S-transferases. J Biol Chem. 1976; 251(20), 6183–6188. DOI 10.1016/S0021-9258(20)81842-0.CrossRefGoogle ScholarPubMed
Manchope, MF, Calixto-Campos, C, Coelho-Silva, L, et al. Naringenin inhibits superoxide anion-induced inflammatory pain: role of oxidative stress, cytokines, Nrf-2 and the NO−cGMP−PKG−KATP channel signaling pathway. PLoS ONE. 2016; 11(4), e0153015. DOI 10.1371/JOURNAL.PONE.0153015.CrossRefGoogle ScholarPubMed
O’Donnell, L. Mechanisms of spermiogenesis and spermiation and how they are disturbed. Spermatogenesis. 2015; 4(2), e979623. DOI 10.4161/21565562.2014.979623.CrossRefGoogle ScholarPubMed
Moreno, RD, Alvarado, CP. The mammalian acrosome as a secretory lysosome: new and old evidence. Mol Reprod Dev. 2006; 73(11), 1430–1434. DOI 10.1002/MRD.20581.CrossRefGoogle ScholarPubMed
Clermont, Y. Cell biology of mammalian spermiogenesis. Front Endocrinol. 1993, 332–376.Google Scholar
Zhao, L, Burkin, HR, Shi, X, Li, L, Reim, K, Miller, DJ. Complexin I is required for mammalian sperm acrosomal exocytosis. Dev Biol. 2007; 309(2), 236–244. DOI 10.1016/J.YDBIO.2007.07.009.CrossRefGoogle ScholarPubMed
Kang-Decker, N, Mantchev, GT, Juneja, SC, McNiven, MA, Van Deursen, JMA. Lack of acrosome formation in Hrb-deficient mice. Science. 2001; 294, 1531–1533. DOI 10.1126/SCIENCE.1063665/SUPPL_FILE/1063665S1_THUMB.GIF.CrossRefGoogle ScholarPubMed
Marshall, FHA, Cramer, W, Lockhead, J. The Physiology of Reproduction, 1922. Longmans, Green and Company.Google Scholar
Dutta, S, Majzoub, A, Agarwal, A. Oxidative stress and sperm function: a systematic review on evaluation and management. Arab J Urol. 2019; 17(2), 87–97. DOI 10.1080/2090598X.2019.1599624.CrossRefGoogle ScholarPubMed
Bansal, AK, Bilaspuri, GS. Impacts of oxidative stress and antioxidants on semen functions. Vet Med Int. 2011; 2011, 1–7. DOI 10.4061/2011/686137.CrossRefGoogle Scholar
Kim, JG, Parthasarathy, S. Oxidation and the spermatozoa. Semin Reprod Endocr. 1998; 16(04), 235–239. DOI 10.1055/S-2007-1016283.CrossRefGoogle ScholarPubMed
Kocabaş, M, Kutluyer, F, Benzer, F, Erişir, M. Malathion-induced spermatozoal oxidative damage and alterations in sperm quality of endangered trout Salmo coruhensis. Environ Sci Pollut Res. 2018; 25(3), 2588–2593. DOI 10.1007/s11356-017-0700-0.CrossRefGoogle ScholarPubMed
Slimen, S, Saloua, EF, Najoua, G. Oxidative stress and cytotoxic potential of anticholinesterase insecticide, malathion in reproductive toxicology of male adolescent mice after acute exposure. Iran J Basic Med Sci. 2014; 17(7), 522–530.Google ScholarPubMed
Selmi, S, Tounsi, H, Safra, I, et al. Histopathological, biochemical and molecular changes of reproductive function after malathion exposure of prepubertal male mice. RSC Adv. 2015; 5(18), 13743–13753. DOI 10.1039/C4RA16516K.CrossRefGoogle Scholar
Miller, WL. Role of mitochondria in steroidogenesis. Endocrin Dev. 2011; 20, 1–19. DOI 10.1159/000321204.CrossRefGoogle ScholarPubMed
Collins, LL, Chang, C. Androgens and the androgen receptor in male sex development and fertility. In Androg. Androg. Recept. Mech. Funct. Clin. Appl. (eds. Norwell, MA), 2002; pp. 299–323. Kluwer Academic Publishers, Boston, MA, 10.1007/978-1-4615-1161-8_14)CrossRefGoogle Scholar
Qiu, LL, Wang, X, hui Zhang, X, et al. Decreased androgen receptor expression may contribute to spermatogenesis failure in rats exposed to low concentration of bisphenol A. Toxicol Lett. 2013; 219(2), 116–124. DOI 10.1016/J.TOXLET.2013.03.011.CrossRefGoogle ScholarPubMed
Chen, S-R, Liu, Y-X. Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling. Reproduction. 2015; 149(4), 159–167. DOI 10.1530/REP-14-0481.CrossRefGoogle ScholarPubMed
Vandenberg, LN. Low dose effects and nonmonotonic dose responses for endocrine disruptors. Endocr Disrupt Hum Health. 2022, 141–163. DOI 10.1016/B978-0-12-821985-0.00006-2.CrossRefGoogle Scholar
Darghouthi, M, Rezg, R, Boughmadi, O, Mornagui, B. Low-dose bisphenol S exposure induces hypospermatogenesis and mitochondrial dysfunction in rats: a possible implication of StAR protein. Adv Exp Med Biol. 2022; 107, 104–111. DOI 10.1016/J.REPROTOX.2021.11.007.Google ScholarPubMed
Yaglova, NV, Tsomartova, DA, Obernikhin, SS, et al. Differential disrupting effects of prolonged low-dose exposure to dichlorodiphenyltrichloroethane on androgen and estrogen production in males. Int J Mol Sci. 2021; 22(6), 1–11. DOI 10.3390/IJMS22063155.CrossRefGoogle ScholarPubMed
Chaturvedi, NK, Kumar, S, Negi, S, Tyagi, RK. Endocrine disruptors provoke differential modulatory responses on androgen receptor and pregnane and xenobiotic receptor: potential implications in metabolic disorders. Mol Cell Biochem. 2010; 345, 291–308. DOI 10.1007/S11010-010-0583-6/FIGURES/6.CrossRefGoogle ScholarPubMed
Guintivano, J, Kaminsky, ZA. Role of epigenetic factors in the development of mental illness throughout life. Neurosci Res. 2016; 102, 56–66. DOI 10.1016/J.NEURES.2014.08.003.CrossRefGoogle ScholarPubMed
Zhang, X, Ho, SM. Epigenetics meets endocrinology. J Mol Endocrinol. 2011; 46(1), R11–R32. DOI 10.1677/JME-10-0053.CrossRefGoogle ScholarPubMed
Angel Sánchez-Garrido, M, Garc Ia-Galiano, D, Tena-Sempere, M. Early programming of reproductive health and fertility: novel neuroendocrine mechanisms and implications in reproductive medicine. Hum Reprod Update. 2022; 28(3), 346–375. DOI 10.1093/HUMUPD/DMAC005.CrossRefGoogle Scholar