Animal Reproduction (AR)
Animal Reproduction (AR)

Arsenic exposure and its implications in male fertility

Mariana Machado-Neves

Downloads: 0
Views: 52


Arsenic exposure is a global health concern. This toxic metalloid is ubiquitous in the environment and contaminates food and drinking water. Once ingested, it undergoes a complex metabolic process within the body, which contributes to its accumulation and reactivity. Arsenic toxicity stems from the induction of oxidative stress, inhibition of thiol-containing proteins, and mimicry of inorganic phosphates. Arsenic poisoning is associated with the development of reproductive disorders. In males, arsenic causes a reduction in testicular weight and alterations in steroidogenesis and spermatogenesis. Moreover, it reduces the number and quality of spermatozoa harvested from the cauda epididymis. The mitochondria are targets of arsenic toxicity because of the production of free radicals and their high content of cysteine-rich proteins and fatty acids. Mitochondrial dysfunction may contribute to reproductive disorders because this organelle is crucial for controlling testicular and epididymal events related to sperm production and maturation. All of these alterations mediated by arsenic exposure contribute to the failure of male reproductive competence by reducing gamete viability. This review describes the potential mechanisms of arsenic toxicity, its detrimental effects on male reproductive organs, and consequences on sperm fertility.


arsenite, epididymis, male reproduction, oxidative stress, mitochondria


Abdul KSM, Jayasinghe SS, Chandana EPS, Jayasumana C, Silva PMCS. Arsenic and human health effects: A review. Environ Toxicol Pharmacol. 2015;40(3):828-46. PMid:26476885.

Aitken RJ, Gibb Z, Baker MA, Drevet J, Gharagozloo P. Causes and consequences of oxidative stress in spermatozoa. Reprod Fertil Dev. 2016;28(2):1-10. PMid:27062870.

Aitken RJ, Jones KT, Robertson S. Reactive oxygen species and sperm function - in sickness and in health. J Androl. 2012;33(6):1096-106. PMid:22879525.

Aitken RJ. Impact of oxidative stress on male and female germ cells: implications for fertility. Reproduction. 2020;159(4):R189-201. PMid:31846434.

Araújo-Ramos AT, Basso CG, Passoni MT, Ribeiro DCK, Spercoski KM, Oliveira JM, Romano RM, Merino C, Sandri JMM, Almeida MF, Predes FS, Martino-Andrade AJ. The endocrine disrupting effects of sodium arsenite in the rat testis is not mediated through macrophage activation. Reprod Toxicol. 2021;102:1-9. PMid:33766721.

Aydin Y, Orta-Yilmaz B. Synergistic effects of arsenic and fluoride on oxidative stress and apoptotic pathway in Leydig and Sertoli cells. Toxicology. 2022;475:153241. PMid:35714946.

Breton S, Nair AV, Battistone MA. Epithelial dynamics in the epididymis: role in the maturation, protection, and storage of spermatozoa. Andrology. 2019;7(5):631-43. PMid:31044554.

Breton S, Ruan YC, Park Y-J, Kim B. Regulation of epithelial function, differentiation, and remodeling in the epididymis. Asian J Androl. 2016;18(1):3-9. PMid:26585699.

Chen H, Liu G, Qiao N, Kang Z, Hu L, Liao J, Yang F, Pang C, Liu B, Zeng Q, Li Y, Li Y. Toxic effects of arsenic trioxide on spermatogonia are associated with oxidative stress, mitochondrial dysfunction, autophagy and metabolomic alterations. Ecotoxicol Environ Saf. 2020;190:110063. PMid:31846860.

Chianese R, Pierantoni R. Mitochondrial reactive oxygen species (ROS) production alters sperm quality. Antioxidants. 2021;10(1):92. PMid:33440836.

Couto-Santos F, Souza ACF, Bastos DSS, Ervilha LOG, Dias FCR, Araújo LS, Guimarães SEF, Oliveira LL, Machado-Neves M. Prepubertal exposure to arsenic alters male reproductive parameters in pubertal and adult rats. Toxicol Appl Pharmacol. 2020;409:115304. PMid:33127376.

Couto-Santos F, Viana AGA, Souza ACF, Dutra AAA, Mendes TAO, Ferreira ATS, Aguilar JEP, Oliveira LL, Machado-Neves M. Prepubertal arsenic exposure alters phosphoproteins profile, quality, and fertility of epididymal spermatozoa in sexually mature rats. Toxicology. 2021;460:152886. PMid:34352348.

Das A, Joardar M, Chowdhury NR, De A, Mridha D, Roychowdhury T. Arsenic toxicity in livestock growing in arsenic endemic and control sites of West Bengal: risk for human and environment. Environ Geochem Health. 2021;43(8):3005-25. PMid:33492570.

Domeniconi RF, Souza ACF, Xu B, Washington AM, Hinton BT. Is the epididymis a series of organs placed side by side? Biol Reprod. 2016;95(1):10. PMid:27122633.

Filomeni G, Zio D, Cecconi F. Oxidative stress and autophagy: the clash between damage and metabolic needs. Cell Death Differ. 2015;22(3):377-88. PMid:25257172.

Guvvala PR, Ravindra JP, Selvaraju S. Impact of environmental contaminants on reproductive health of male domestic ruminants: a review. Environ Sci Pollut Res Int. 2020;27(4):3819-36. PMid:31845245.

Guvvala PR, Sellappan S, Parameswaraiah RJ. Impact of arsenic(V) on testicular oxidative stress and sperm functional attributes in Swiss albino mice. Environ Sci Pollut Res Int. 2016;23(18):18200-10. PMid:27265425.

Han Y, Liang C, Manthari RK, Yu Y, Gao Y, Liu Y, Jiang S, Tikka C, Wang J, Zhang J. Arsenic influences spermatogenesis by disorganizing the elongation of spermatids in adult male mice. Chemosphere. 2020a;238:124650. PMid:31472347.

Han Y, Liang C, Yu Y, Manthari RK, Cheng C, Tan Y, Li X, Tian X, Fu W, Yang J, Yang W, Xing Y, Wang J, Zhang J. Chronic arsenic exposure lowered sperm motility via impairing ultramicrostructure and key proteins expressions of sperm acrosome and flagellum formation during spermiogenesis in male mice. Sci Total Environ. 2020b;734:139233. PMid:32460071.

Hardneck F, Israel G, Pool E, Maree L. Quantitative assessment of heavy metal effects on sperm function using computer-aided sperm analysis and cytotoxicity assays. Andrologia. 2018;50(10):e13141. PMid:30225848.

Hirano S. Biotransformation of arsenic and toxicological implication of arsenic metabolites. Arch Toxicol. 2020;94(8):2587-601. PMid:32435915.

Hu Y, Li J, Lou B, Wu R, Wang G, Lu C, Wang H, Pi J, Xu Y. The role of reactive oxygen species in arsenic toxicity. Biomolecules. 2020;10(2):240. PMid:32033297.

Jomova K, Jenisova Z, Feszterova M, Baros S, Liska J, Hudecova D, Rhodes CJ, Valko M. Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol. 2011;31(2):95-107. PMid:21321970.

Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicology. 2011;283(2-3):65-87. PMid:21414382.

Jones DP. Radical-free biology of oxidative stress. Am J Physiol Cell Physiol. 2008;295(4):C849-68. PMid:18684987.

Kim YJ, Kim JM. Arsenic toxicity in male reproduction and development. Dev Reprod. 2015;19(4):167-80. PMid:26973968.

Lima GDA, Sertorio MN, Souza ACF, Menezes TP, Mouro VGS, Gonçalves NM, Oliveira JM, Henry M, Machado-Neves M. Fertility in male rats: disentangling adverse effects of arsenic compounds. Reprod Toxicol. 2018;78:130-40. PMid:29702248.

Machado-Neves M, Souza ACF. The effect of arsenical compounds on mitochondrial metabolism. In: Oliveira M, editor. Mitochondrial intoxication. Amsterdam: Elsevier; 2022. p. 379-407.

Machado-Neves M. Effect of heavy metals on epididymal morphology and functions: an integrative review. Chemosphere. 2022;291(Pt 2):133020. PMid:34848222.

Medeiros PC, Samelo RR, Silva APG, Santiago MSA, Duarte FA, Castro IB, Perobelli JE. Prepubertal exposure to low doses of sodium arsenite impairs spermatogenesis and epididymal histophysiology in rats. Environ Toxicol. 2019;34(1):83-91. PMid:30291770.

Miyaso H, Ogawa Y, Itoh M. Microenvironment for spermatogenesis and sperm maturation. Histochem Cell Biol. 2022;157(3):273-85. PMid:35247091.

Moldogazieva NT, Mokhosoev IM, Feldman NB, Lutsenko SV. ROS and RNS signalling: adaptative redox switches through oxidative/nitrosative protein modifications. Free Radic Res. 2018;52(5):507-43. PMid:29589770.

Nowicka-Bauer K, Nixon B. Molecular changes induced by oxidative stress that impair human sperm motility. Antioxidants. 2020;9(2):134. PMid:32033035.

O’Flaherty C, Matsushita-Fournier D. Reactive oxygen species and protein modifications in spermatozoa. Biol Reprod. 2017;97(4):577-85. PMid:29025014.

O’Flaherty C. Orchestrating the antioxidant defenses in the epididymis. Andrology. 2019;7(5):662-8. PMid:31044545.

Ommati MM, Heidari R, Manthari RK, Chiranjeevi ST, Niu R, Sun Z, Sabouri S, Zamiri MJ, Zaker L, Yuan J, Wang J, Zhang J, Wang J. Paternal exposure to arsenic resulted in oxidative stress, autophagy, and mitochondrial impairments in the HPG axis of pubertal male offspring. Chemosphere. 2019;236:124325. PMid:31326754.

Park Y-J, Pang M-G. Mitochondrial functionality in male fertility: from spermatogenesis to fertilization. Antioxidants. 2021;10(1):98. PMid:33445610.

Prakash C, Chhikara S, Kumar V. Mitochondrial dysfunction in arsenic-induced hepatotoxicity: pathogenic and therapeutic implications. Biol Trace Elem Res. 2022;200(1):261-70. PMid:33566285.

Prakash C, Soni M, Kumar V. Mitochondrial oxidative stress and dysfunction in arsenic neurotoxicity: a review. J Appl Toxicol. 2016;36(2):179-88. PMid:26510484.

Rahaman MS, Rahman MM, Mise N, Sikder MT, Ichihara G, Uddin MK, Kurasaki M, Ichihara S. Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management. Environ Pollut. 2021;289:117940. PMid:34426183.

Ribeiro IM, Viana AGZ, Carvalho RPR, Waddington B, Machado-Neves M. Could metal exposure affect sperm parameters of domestic ruminants? A meta-analysis. Anim Reprod Sci. 2022;244:107050. PMid:35930938.

Shen S, Li X, Cullen WR, Weinfeld M, Le XC. Arsenic binding to proteins. Chem Rev. 2013;113(10):7769-92. PMid:23808632.

Souza ACF, Bastos DSS, Sertorio MN, Santos FC, Ervilha LOG, Oliveira LL, Machado-Neves M. Combined effects of arsenic exposure and diabetes on male reproductive functions. Andrology. 2019;7(5):730-40. PMid:31207180.

Souza ACF, Marchesi SC, Ferraz RP, Lima GD, Oliveira JA, Machado-Neves M. Effects of sodium arsenate and arsenite on male reproductive functions in Wistar rats. J Toxicol Environ Health A. 2016a;79(6):274-86. PMid:27029432.

Souza ACF, Marchesi SC, Lima GDA, Ferraz RP, Santos FC, Matta SLP, Machado-Neves M. Effects of sodium arsenite and arsenate in testicular histomorphometry and antioxidant enzymes activities in rats. Biol Trace Elem Res. 2016b;171(2):354-62. PMid:26446860.

Sun J, Yu G, Zhang Y, Liu X, Du C, Wang L, Li Z, Wang C. Heavy metal level in human semen with different fertility: a meta-analysis. Biol Trace Elem Res. 2017;176(1):27-36. PMid:27444304.

Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. In: Luch A, editor. Molecular, clinical and environmental toxicology. Basel: Birkhauser; 2012. p. 133-64.

Thomas DJ. Arsenic methylation - lessons from three decades of research. Toxicology. 2021;457:152800. PMid:33901604.

Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12(10):1161-208. PMid:15892631.

Verma R, Vijayalakshmy K, Chaudhiry V. Detrimental impacts of heavy metals on animal reproduction: a review. J Entomol Zool Stud. 2018;6(6):27-30.

Wang A, Holladay SD, Wolf DC, Ahmed SA, Robertson JL. Reproductive and developmental toxicity of arsenic in rodents: a review. Int J Toxicol. 2006;25(5):319-31. PMid:16940004.

Watanabe T, Hirano S. Metabolism of arsenic and its toxicological relevance. Arch Toxicol. 2013;87(6):969-79. PMid:22811022.

Wirth JJ, Mijal RS. Adverse effects of low level heavy metal exposure on male reproductive function. Syst Biol Reprod Med. 2010;56(2):147-67. PMid:20377313.

Wrzecińska M, Kowalczyk A, Cwynar P, Czerniawska-Piatkowska E. Disorders of the reproductive health of cattle as a response to exposure to metals. Biology. 2021;10(9):882. PMid:34571759.

Wu PY, Scarlata E, O’Flaherty C. Long-term adverse effects of oxidative stress on rat epididymis and spermatozoa. Antioxidants. 2020;9(2):170. PMid:32093059.

Wu X, Cobbina SJ, Mao G, Xu H, Zhang Z, Yang L. A review of toxicity and mechanisms of individual and mixtures of heavy metals in the enviroment. Environ Sci Pollut Res Int. 2016;23(9):8244-59. PMid:26965280.

Zeng Q, Yi H, Huang L, An Q, Wang H. Reduced testosterone and DDX3y expression caused by long-term exposure to arsenic and its effect on spermatogenesis in mice. Environ Toxicol Pharmacol. 2018;63:84-91. PMid:30189373.

Zhang Z, Miao J, Wang Y. Mitochondrial regulation in spermatogenesis. Reproduction. 2022;163(4):R55-69. PMid:35084362.

Zubair M, Ahmad M, Qureshi ZI. Review on arsenic-induced toxicity in male reproductive system and its amelioration. Andrologia. 2017;49(9):e12791. PMid:28133775.

Submitted date:

Accepted date:

63e393fda953957ac62e3663 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections