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2024 Vol.51, Issue 2 Preview Page

Animal

Exposure to ethylene thiourea degrades the sperm ability of mammals
Adikari Arachchige Dilki Indrachapa Adikari1
,
Malavi Arachchi Gamage Nayodya Dananjanee Malavi Arachchi Gamage1
,
Wijesooriya Mudhiyanselage Nadeema Dissanayake1
,
Jung Min Heo2
,
Young-Joo Yi1*
1Department of Agricultural Education, College of Education, Sunchon National University, Suncheon 57922, Korea
2Department of Animal Science and Biotechnology, College of Agriculture and Life Sciences, Chungnam National University, Daejeon 34134, Korea
*Corresponding Author
1 June 2024. pp. 109-121
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Abstract

Mancozeb is a manganese and zinc-containing fungicide that belongs to the ethylene bis-dithiocarbamate group and produces ethylene thiourea (ETU) after biotransformation or environmental degradation, which has toxicological hazard owing to its known antithyroid properties. Although mancozeb leads to negative changes in fertility capacity, the effects of ETU are less known. Therefore, this study examined the alteration of fertilization competence in boar spermatozoa exposed to ETU. The sperm motility, motion kinematics, viability, acrosome integrity, chromatin stability, and intracellular reactive oxygen species (ROS) production of sperm subjected to various ETU concentrations (10, 50, 100, and 200 µM) were evaluated after two different incubation times (30 min and 2 hrs). In addition, the relative mRNA expression of the sperm functional proteins was analyzed after exposure to ETU. A dose-dependent motility reduction was observed in sperm exposed to ETU during both incubation periods compared to the controls. The motion kinematics were reduced significantly in sperm incubated with ETU. Higher percentages of viable sperm were observed in the controls, while such viability was decreased significantly in sperm with 10 - 200 µM ETU. The acrosome integrity was particularly damaged on sperm incubated with 10 - 200 µM ETU for 30 min. Higher intracellular ROS levels were produced in sperm exposed to 200 µM ETU. In addition, lower relative levels of AKAP3, AKAP4, ODF2, and ZPBP2 expression were observed in sperm exposed to ETU compared to the controls. Mancozeb and ETU could adversely affect the reproductive functions of mammals. Hence, the effects of ETU on the reproductive system should be examined further.

Keywords
boar
ethylene thiourea
fertilization
pesticide metabolites
spermatozoa
References
1

Adikari AA, Moon ST, Yi YJ. 2022. Deterioration in the fertilization capability of boar spermatozoa upon exposure to mancozeb. Korean Journal of Agricultural Science 49:259-267.

10.7744/kjoas.20220023
2

Aktar MW, Paramasivam M, Sengupta D, Purkait S, Ganguly M, Banerjee S. 2009. Impact assessment of pesticide residues in fish of Ganga river around Kolkata in West Bengal. Environmental Monitoring and Assessment 157:97-104.

10.1007/s10661-008-0518-918758975
3

Aruldhas MM, Ramalingam N, Jaganathan A, John Sashi AM, Stanley JA, Nagappan AS, Vasavan J, Kannan A, Seshadri VN. 2010. Gestational and neonatal-onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood. The Prostate 70:689-700.

10.1002/pros.2110120033886
4

Asadi N, Bahmani M, Kheradmand A, Rafieian-Kopaei M. 2017. The impact of oxidative stress on testicular function and the role of antioxidants in improving it: A review. Journal of Clinical and Diagnostic Research 11:IE01-IE05.

10.7860/JCDR/2017/23927.988628658802PMC5483704
5

Axelstad M, Boberg J, Nellemann C, Kiersgaard M, Jacobsen PR, Christiansen S, Hougaard KS, Hass U. 2011. Exposure to the widely used fungicide mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring. Toxicological Sciences 120:439-446.

10.1093/toxsci/kfr00621266532
6

Ayala A, Muñoz MF, Argüelles S. 2014. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity 2014:360438.

10.1155/2014/36043824999379PMC4066722
7

Berger T. 1990. Pisum sativum agglutinin used as an acrosomal stain of porcine and caprine sperm. Theriogenology 33:689-695.

10.1016/0093-691X(90)90546-616726765
8

Blommaert D, Sergeant N, Delehedde M, Jouy N, Mitchell V, Franck T, Donnay I, Lejeune JP, Serteyn D. 2019. Expression, localization, and concentration of A-kinase anchor protein 4 (AKAP4) and its precursor (proAKAP4) in equine semen: Promising marker correlated to the total and progressive motility in thawed spermatozoa. Theriogenology 131:52-60.

10.1016/j.theriogenology.2019.03.01130947075
9

Calogero AE, Condorelli RA, Russo GI, La Vignera S. 2017. Conservative nonhormonal options for the treatment of male infertility: Antibiotics, anti-inflammatory drugs, and antioxidants. Biomedical Research International. 2017:4650182.

10.1155/2017/465018228164122PMC5253172
10

Chandrasekhar Y, Holland MK, D'Occhio MJ, Setchell BP. 1985. Spermatogenesis, seminal characteristics and reproductive hormone levels in mature rams with induced hypothyroidism and hyperthyroidism. Journal of Endocrinology 105:39-46.

10.1677/joe.0.10500393921644
11

Dearfield KL. 1994. Ethylene thiourea (ETU). A review of the genetic toxicity studies. Mutation Research/Reviews in Genetic Toxicology 317:111-132.

10.1016/0165-1110(94)90020-57511791
12

Devi PA, Paramasivam M, Prakasam V. 2015. Degradation pattern and risk assessment of carbendazim and mancozeb in mango fruits. Environmental Monitoring and Assessment 187:1-6.

10.1007/s10661-014-4142-625407993
13

Gao Y, Lee WM, Cheng CY. 2014. Thyroid hormone function in the rat testis. Frontiers in Endocrinology 5:188.

10.3389/fendo.2014.0018825414694PMC4220729
14

Gavrilescu M, Demnerová K, Aamand J, Agathos S, Fava F. 2015. Emerging pollutants in the environment: Present and future challenges in biomonitoring, ecological risks and bioremediation. New Biotechnology 32:147-156.

10.1016/j.nbt.2014.01.00124462777
15

Greenlee AR, Ellis TM, Berg RL. 2004. Low-dose agrochemicals and lawn-care pesticides induce developmental toxicity in murine preimplantation embryos. Environmental Health Perspectives 112:703-709.

10.1289/ehp.677415121514PMC1241965
16

Hernandez A. 2018. Thyroid hormone role and economy in the developing testis. Vitamins and Hormones 106:473-500.

10.1016/bs.vh.2017.06.00529407445
17

Jacobsen OS, Bossi R. 1997. Degradation of ethylenethiourea (ETU) in oxic and anoxic sandy aquifers. FEMS Microbiology Reviews 20:539-544.

10.1111/j.1574-6976.1997.tb00336.x9340001
18

Kozlovsky P, Gefen A. 2013. Sperm penetration to the zona pellucida of an oocyte: A computational model incorporating acrosome reaction. Computer Methods Biomechanics and Biomedical Engineering 16:1106-1111.

10.1080/10255842.2013.76861823477851
19

Ksheerasagar RL, Kaliwal BB. 2003. Temporal effects of mancozeb on testes, accessory reproductive organs and biochemical constituents in albino mice. Environmental Toxicology and Pharmacology 15:9-17.

10.1016/j.etap.2003.08.00621782674
20

Ksheerasagar RL, Kaliwal BB. 2010. Effect of mancozeb on thyroid, testis, accessory reproductive organs and biochemical constituents in albino mice. Recent Research in Science and Technology 2:7-17.

21

Lin YN, Roy A, Yan W, Burns KH, Matzuk MM. 2007. Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Molecular and Cell Biology 27:6794-6805.

10.1128/MCB.01029-0717664285PMC2099232
22

Mandić-Rajćević S, Rubino FM, Colosio C. 2020. Establishing health-based biological exposure limits for pesticides: A proof of principle study using mancozeb. Regulatory Toxicology and Pharmacology 115:104689.

10.1016/j.yrtph.2020.10468932544413
23

Maran RR, Arunakaran J, Aruldhas MM. 2000. T3 directly stimulates basal and modulates LH induced testosterone and oestradiol production by rat Leydig cells in vitro. Endocrine Journal 47:417-428.

10.1507/endocrj.47.41711075722
24

Marinovich M, Guizzetti M, Ghilardi F, Viviani B, Corsini E, Galli CL. 1997. Thyroid peroxidase as toxicity target for dithiocarbamates. Archives of Toxicology 71:508-512.

10.1007/s0020400504209248629
25

Martins CF, Dode MN, Báo SN, Rumpf R. 2007. The use of the acridine orange test and the TUNEL assay to assess the integrity of freeze-dried bovine spermatozoa DNA. Genetics and Molecular Research 6:94-104.

17469058
26

Miki K, Willis WD, Brown PR, Goulding EH, Fulcher KD, Eddy EM. 2002. Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility. Developmental Biology 248:331-342.

10.1006/dbio.2002.072812167408
27

Mingo V, Lötters S, Wagner N. 2017. The impact of land use intensity and associated pesticide applications on fitness and enzymatic activity in reptiles-A field study. Science of the Total Environment 590:114-124.

10.1016/j.scitotenv.2017.02.17828259431
28

Mohammadi-Sardoo M, Mandegary A, Nabiuni M, Nematollahi-Mahani SN, Amirheidari B. 2018. Mancozeb induces testicular dysfunction through oxidative stress and apoptosis: Protective role of N-acetylcysteine antioxidant. Toxicology and Industrial Health 34:798-811.

10.1177/074823371877839730037311
29

Pandey SP, Mohanty B. 2015. The neonicotinoid pesticide imidacloprid and the dithiocarbamate fungicide mancozeb disrupt the pituitary-thyroid axis of a wildlife bird. Chemosphere 122:227-234.

10.1016/j.chemosphere.2014.11.06125496744
30

Paramasivam M, Chandrasekaran S. 2013. Dynamics and residues of mixed formulation of fenamidone and mancozeb in gherkin field ecosystem. Ecotoxicology and Environmental Safety 98:292-296.

10.1016/j.ecoenv.2013.08.00624041529
31

Pirozzi AVA, Stellavato A, La Gatta A, Lamberti M, Schiraldi C. 2016. Mancozeb, a fungicide routinely used in agriculture, worsens nonalcoholic fatty liver disease in the human HepG2 cell model. Toxicology Letters 249:1-4.

10.1016/j.toxlet.2016.03.00427016407
32

Pursel VG, Johnson LA. 1976. Frozen boar spermatozoa: Methods of thawing pellets. Journal of Animal Science 42:927-931.

10.2527/jas1976.424927x1262291
33

Rey F, González M, Zayas MA, Stoker C, Durando M, Luque EH, Muñoz-de-Toro M. 2009. Prenatal exposure to pesticides disrupts testicular histoarchitecture and alters testosterone levels in male Caiman latirostris. General and Comparative Endocrinology 162:286-292.

10.1016/j.ygcen.2009.03.03219364509
34

Rijntjes E, Swarts HJ, Anand-Ivell R, Teerds KJ. 2009. Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development. American Journal of Physiology-Endocrinology and Metabolism 296:305-314.

10.1152/ajpendo.90750.200819033542
35

Rossi G, Palmerini MG, Macchiarelli G, Buccione R, Cecconi S. 2006. Mancozeb adversely affects meiotic spindle organization and fertilization in mouse oocytes. Reproductive Toxicology 22:51-55.

10.1016/j.reprotox.2005.11.00516406479
36

Runkle J, Flocks J, Economos J, Dunlop AL. 2017. A systematic review of mancozeb as a reproductive and developmental hazard. Environment International 99:29-42.

10.1016/j.envint.2016.11.00627887783
37

Spinaci M, Nerozzi C, Mislei B, Blanco-Prieto O, Mari G, Galeati G, Bucci D. 2022. Impact of glyphosate and its formulation Roundup® on stallion spermatozoa. Theriogenology 79:197-203.

10.1016/j.theriogenology.2021.12.00334891125
38

Srivastava AK, Ali W, Singh R, Bhui K, Tyagi S, Al-Khedhairy AA, Srivastava PK, Musarrat J, Shukla Y. 2012. Mancozebinduced genotoxicity and apoptosis in cultured human lymphocytes. Life Sciences 90:815-824.

10.1016/j.lfs.2011.12.01322289270
39

Suárez ERL, Geissen V, Sánchez AJ, Chan RAC, Bello-Mendoza R. 2013. Formation and decay of ethylenethiourea (ETU) in soil and water under tropical conditions. Journal of Plant Nutrition and Soil Science 176:40-46.

10.1002/jpln.201200014
40

Veeramachaneni DR. 2000. Deteriorating trends in male reproduction: Idiopathic or environmental? Animal Reproduction Science 60:121-130.

10.1016/S0378-4320(00)00113-510844189
41

Wagner MS, Wajner SM, Maia AL. 2009. Is there a role for thyroid hormone on spermatogenesis? Microscopy Research and Technique 72:796-808.

10.1002/jemt.2075919637394
42

Wang Z, Kottawatta KS, Kodithuwakku SP, Fernando TS, Lee YL, Ng EH, Yeung WS, Lee KF. 2021. The fungicide Mancozeb reduces spheroid attachment onto endometrial epithelial cells through downregulation of estrogen receptor β and integrin β3 in Ishikawa cells. Ecotoxicology and Environmental Safety 208:111606.

10.1016/j.ecoenv.2020.11160633396126
43

WHO (World Health Organization). 1988. Dithiocarbamate pesticides, ethylenethiourea and propylenethiourea: A general introduction. Environmental Health Criteria No 78. WHO, Geneva, Swiss.

44

Xu K, Yang L, Zhang L, Qi H. 2020. Lack of AKAP3 disrupts integrity of the subcellular structure and proteome of mouse sperm and causes male sterility. Development 147:dev181057.

10.1242/dev.18105731969357
45

Yi YJ, Adikari AADI, Moon ST, Lee SM, Heo JM. 2021. Effects of lipopolysaccharides on the maturation of pig oocytes. Korean Journal of Agricultural Science 48:163-170.

10.7744/kjoas.20210010
46

Zhao W, Li Z, Ping P, Wang G, Yuan X, Sun F. 2018. Outer dense fibers stabilize the axoneme to maintain sperm motility. Journal of Cellular and Molecular Medicine 22:1755-1768.

10.1111/jcmm.1345729168316PMC5824370
47

Zhou R, Wu J, Liu B, Jiang Y, Chen W, Li J, He Q, He Z. 2019. The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis. Cellular and Molecular Life Sciences 76:2681-2695.

10.1007/s00018-019-03101-930980107PMC11105226
Information
  • Publisher :Institute of Agricultural Science, Chungnam National University
  • Publisher(Ko) :충남대학교 농업과학연구소
  • Journal Title :Korean Journal of Agricultural Science
  • Journal Title(Ko) :농업과학연구
  • Volume : 51
  • No :2
  • Pages :109-121
  • Received Date : 2024-02-07
  • Revised Date : 2024-03-19
  • Accepted Date : 2024-03-22
  • DOI :https://doi.org/10.7744/kjoas.510202
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