Evidence for Ovarian and Testicular Toxicities of Cadmium and Detoxification by Natural Substances
Abstract
:1. Introduction
2. Environmental Cadmium Exposure and Human Reproduction
2.1. Dietary Intake Levels of Cadmium
2.2. Effects of Cadmium on Human Reproduction
2.3. Cadmium Exposure Estimates
2.4. Epidemiological Investigations on Effects of Cadmium on Fecundity in Women
2.5. Epidemiological Investigations on Effects of Cadmium on Fecundity in Men
3. Metal Binding Proteins in the Ovary and Testis
4. The Cellular Toxic Mechanisms of Cadmium
5. Experimental Trials to Mitigate Ovarian Toxicity
6. Experimental Trials to Mitigate Testicular Toxicity
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Cadmium; Department of Health and Humans Services, Public Health Service, Centers for Disease Control and Prevention: Atlanta, GA, USA, 2012. [Google Scholar]
- WHO. IPCS (International Programme on Chemical Safety) Environmental Health Criteria 134: Cadmium; WHO: Geneva, Switzerland, 1992. [Google Scholar]
- Järup, L. Hazards of heavy metal contamination. Br. Med. Bull. 2003, 68, 167–182. [Google Scholar] [CrossRef] [Green Version]
- Garrett, R.G. Natural sources of metals to the environment. Hum. Ecol. Risk Assess. 2010, 6, 945–963. [Google Scholar] [CrossRef]
- Satarug, S.; Phelps, K.R. Cadmium Exposure and Toxicity. In Metal Toxicology Handbook; Bagchi, D., Bagchi, M., Eds.; CRC Press: Boca Raton, FL, USA, 2021; pp. 219–274. [Google Scholar]
- Lamb, D.T.; Kader, M.; Ming, H.; Wang, L.; Abbasi, S.; Megharaj, M.; Naidu, R. Predicting plant uptake of cadmium: Validated with long-term contaminated soils. Ecotoxicology 2016, 25, 1563–1574. [Google Scholar] [CrossRef] [PubMed]
- Satarug, S.; Vesey, D.A.; Gobe, G.C. Current health risk assessment practice for dietary cadmium: Data from different countries. Food Chem. Toxicol. 2017, 106, 430–445. [Google Scholar] [CrossRef]
- Satarug, S. Dietary cadmium intake and its effects on kidneys. Toxics 2018, 6, 15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Capcarová, M.; Harangozó, L.; Árvay, J.; Tóth, T.; Gabriny, L.; Binkowski, L.J.; Palšová, L.; Skalická, M.; Pardo, M.L.G.; Stawarz, R.; et al. Essential and xenobiotic elements in cottage cheese from the Slovak market with a consumer risk assessment. J. Environ. Sci. Health B. 2020, 55, 677–686. [Google Scholar] [CrossRef] [PubMed]
- Wu, S.; Deng, F.; Hao, Y.; Shima, M.; Wang, X.; Zheng, C.; Wei, H.; Lv, H.; Lu, X.; Huang, J.; et al. Chemical constituents of fine particulate air pollution and pulmonary function in healthy adults: The healthy volunteer natural relocation study. J. Hazard. Mater. 2013, 260, 183–191. [Google Scholar] [CrossRef] [PubMed]
- Jung, M.S.; Kim, J.Y.; Lee, H.S.; Lee, C.G.; Song, H.S. Air pollution and urinary N-acetyl-β-glucosaminidase levels in residents living near a cement plant. Ann. Occup. Environ. Med. 2016, 28, 52. [Google Scholar] [CrossRef] [Green Version]
- Jin, Y.; Lu, Y.; Li, Y.; Zhao, H.; Wang, X.; Shen, Y.; Kuang, X. Correlation between environmental low-dose cadmium exposure and early kidney damage: A comparative study in an industrial zone vs. a living quarter in Shanghai, China. Environ. Toxicol. Pharmacol. 2020, 79, 103381. [Google Scholar] [CrossRef] [PubMed]
- Repić, A.; Bulat, P.; Antonijević, B.; Antunović, M.; Džudović, J.; Buha, A.; Bulat, Z. The influence of smoking habits on cadmium and lead blood levels in the Serbian adult people. Environ. Sci. Pollut. Res. Int. 2020, 27, 751–760. [Google Scholar] [CrossRef] [PubMed]
- Pappas, R.S.; Fresquez, M.R.; Watson, C.H. Cigarette smoke cadmium breakthrough from traditional filters: Implications for exposure. J. Anal. Toxicol. 2015, 39, 45–51. [Google Scholar] [CrossRef]
- Satarug, S.; Vesey, D.A.; Gobe, G.C. Health risk assessment of dietary cadmium intake: Do current guidelines indicate how much is safe? Environ. Health Perspect. 2017, 125, 284–288. [Google Scholar] [CrossRef] [PubMed]
- Massányi, P.; Massányi, M.; Madeddu, R.; Stawarz, R.; Lukáč, N. Effects of Cadmium, Lead, and Mercury on the Structure and Function of Reproductive Organs. Toxics 2020, 8, 94. [Google Scholar] [CrossRef] [PubMed]
- Tirpák, F.; Halo, M., Jr.; Tokárová, K.; Binkowski, L.J.; Vašíček, J.; Svoradová, A.; Błaszczyk-Altman, M.; Kováčik, A.; Tvrdá, E.; Chrenek, P.; et al. Composition of Stallion Seminal Plasma and Its Impact on Oxidative Stress Markers and Spermatozoa Quality. Life 2021, 11, 1238. [Google Scholar] [CrossRef] [PubMed]
- Peana, M.; Pelucelli, A.; Medici, S.; Cappai, R.; Nurchi, V.M.; Zoroddu, M.A. Metal Toxicity and Speciation: A review. Curr. Med. Chem. 2021, 28, 7190–7208. [Google Scholar] [CrossRef] [PubMed]
- Khan, W.A.; Arain, M.B.; Soylak, M. Nanomaterials-based solid phase extraction and solid phase microextraction for heavy metals food toxicity. Food Chem. Toxicol. 2020, 145, 111704. [Google Scholar] [CrossRef]
- Rana, M.N.; Tangpong, J.; Rahman, M.M. Toxicodynamics of lead, cadmium, mercury and arsenic-induced kidney toxicity and treatment strategy: A mini review. Toxicol. Rep. 2018, 26, 704–713. [Google Scholar] [CrossRef]
- Zofkova, I.; Davis, M.; Blahos, J. Trace elements have beneficial, as well as detrimental effects on bone homeostasis. Physiol. Res. 2017, 66, 391–402. [Google Scholar] [CrossRef] [PubMed]
- Scientific Opinion of the Panel on Contaminants in the Food Chain on a request from the European Commission on cadmium in food. EFSA J. 2009, 980, 1–139.
- Kim, K.; Melough, M.M.; Vance, T.M.; Noh, H.; Koo, S.I.; Chun, O.K. Dietary cadmium intake and sources in the US. Nutrients 2018, 11, 2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marín, S.; Pardo, O.; Báguena, R.; Font, G.; Yusà, V. Dietary exposure to trace elements and health risk assessment in the region of Valencia, Spain: A total diet study. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2017, 34, 228–240. [Google Scholar] [CrossRef] [PubMed]
- Vromman, V.; Waegeneers, N.; Cornelis, C.; De Boosere, I.; Van Holderbeke, M.; Vinkx, C.; Smolders, E.; Huyghebaert, A.; Pussemier, L. Dietary cadmium intake by the Belgian adult population. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2010, 27, 1665–1673. [Google Scholar] [CrossRef]
- Sand, S.; Becker, W. Assessment of dietary cadmium exposure in Sweden and population health concern including scenario analysis. Food Chem. Toxicol. 2012, 50, 536–544. [Google Scholar] [CrossRef] [PubMed]
- Arnich, N.; Sirot, V.; Rivière, G.; Jean, J.; Noël, L.; Guérin, T.; Leblanc, J.-C. Dietary exposure to trace elements and health risk assessment in the 2nd French Total Diet Study. Food Chem. Toxicol. 2012, 50, 2432–2449. [Google Scholar] [CrossRef] [PubMed]
- Lim, J.A.; Kwon, H.J.; Ha, M.; Kim, H.; Oh, S.Y.; Kim, J.S.; Lee, S.A.; Park, J.D.; Hong, Y.S.; Sohn, S.J.; et al. Korean research project on the integrated exposure assessment of hazardous substances for food safety. Environ. Health Toxicol. 2015, 30, e2015004. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schwarz, M.A.; Lindtner, O.; Blume, K.; Heinemeyer, G.; Schneider, K. Cadmium exposure from food: The German LExUKon project. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2014, 31, 1038–1051. [Google Scholar] [CrossRef]
- Wei, J.; Gao, J.; Cen, K. Levels of eight heavy metals and health risk assessment considering food consumption by China’s residents based on the 5th China total diet study. Sci. Total Environ. 2019, 689, 1141–1148. [Google Scholar] [CrossRef]
- Horiguchi, H.; Oguma, E.; Sasaki, S.; Miyamoto, K.; Hosoi, Y.; Ono, A.; Kayama, F. Exposure assessment of cadmium in female farmers in cadmium-polluted areas in Northern Japan. Toxics 2020, 8, 44. [Google Scholar] [CrossRef] [PubMed]
- Varga, B.; Zsolnai, B.; Paksy, K.; Náray, M.; Ungváry, G. Age dependent accumulation of cadmium in the human ovary. Reprod. Toxicol. 1993, 7, 225–228. [Google Scholar] [CrossRef]
- Oldereid, N.B.; Thomassen, Y.; Attramadal, A.; Olaisen, B.; Purvis, K. Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men. J. Reprod. Fertil. 1993, 99, 421–425. [Google Scholar] [CrossRef] [Green Version]
- Oldereid, N.B.; Thomassen, Y.; Purvis, K. Selenium in human male reproductive organs. Hum. Reprod. 1998, 13, 2172–2176. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sapra, K.J.; Barr, D.B.; Maisog, J.M.; Sundaram, R.; Louis, G.M.B. Time-to-pregnancy associated with couples' use of tobacco products. Nicotine Tob. Res. 2016, 18, 2154–2161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Crinnion, W.J. The CDC fourth national report on human exposure to environmental chemicals: What it tells us about our toxic burden and how it assists environmental medicine physicians. Altern. Med. Rev. 2010, 15, 101–108. [Google Scholar]
- Scott, B.J.; Bradwell, A.R. Identification of the serum binding proteins for iron, zinc, cadmium, nickel, and calcium. Clin. Chem. 1983, 29, 629–633. [Google Scholar] [CrossRef] [PubMed]
- Horn, N.M.; Thomas, A.L. Interactions between the histidine stimulation of cadmium and zinc influx into human erythrocytes. J. Physiol. 1996, 496, 711–718. [Google Scholar] [CrossRef] [PubMed]
- Sagmeister, P.; Gibson, M.A.; McDade, K.H.; Gailer, J. Physiologically relevant plasma d,l-homocysteine concentrations mobilize Cd from human serum albumin. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2016, 1027, 181–186. [Google Scholar] [CrossRef]
- Rokadia, H.K.; Agarwal, S. Serum heavy metals and obstructive lung disease: Results from the National Health and Nutrition Examination Survey. Chest 2013, 143, 388–397. [Google Scholar] [CrossRef]
- Yang, G.; Sun, T.; Han, Y.Y.; Rosser, F.; Forno, E.; Chen, W.; Celedón, J.C. Serum cadmium and lead, current wheeze, and lung function in a nationwide study of adults in the United States. J. Allergy Clin. Immunol. Pract. 2019, 7, 2653–2660.e3. [Google Scholar] [CrossRef]
- Kaneda, M.; Wai, K.M.; Kanda, A.; Ando, M.; Murashita, K.; Nakaji, S.; Ihara, K. Low level of serum cadmium in relation to blood pressures among Japanese general population. Biol. Trace Elem. Res. 2022, 200, 67–75. [Google Scholar] [CrossRef]
- Lee, S.; Min, J.Y.; Min, K.B. Female infertility associated with blood lead and cadmium levels. Int. J. Environ. Res. Public Health 2020, 17, 1794. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jackson, L.W.; Zullo, M.D.; Goldberg, J.M. The association between heavy metals, endometriosis and uterine myomas among premenopausal women: National Health and Nutrition Examination Survey 1999–2002. Hum. Reprod. 2008, 23, 679–687. [Google Scholar] [CrossRef] [Green Version]
- Kim, K.; Pollack, A.Z.; Nobles, C.J.; Sjaarda, L.A.; Zolton, J.R.; Radoc, J.G.; Schisterman, E.F.; Mumford, S.L. Associations between blood cadmium and endocrine features related to PCOS-phenotypes in healthy women of reproductive age: A prospective cohort study. Environ. Health 2021, 20, 64. [Google Scholar] [CrossRef]
- Upson, K.; O’Brien, K.M.; Hall, J.E.; Tokar, E.J.; Baird, D.D. Cadmium exposure and ovarian reserve in women aged 35–49 years: The impact on results from the creatinine adjustment approach used to correct for urinary dilution. Am. J. Epidemiol. 2021, 190, 116–124. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pan, W.; Ye, X.; Zhu, Z.; Li, C.; Zhou, J.; Liu, J. Urinary cadmium concentrations and risk of primary ovarian insufficiency in women: A case-control study. Environ. Geochem. Health 2021, 43, 2025–2035. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.M.; Chung, H.W.; Jeong, K.; Sung, Y.A.; Lee, H.; Ye, S.; Ha, E.H. Association between cadmium and anti-Mullerian hormone in premenopausal women at particular ages. Ann. Occup. Environ. Med. 2018, 30, 44. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. WHO Manual for the Examination and Processing of Human Semen, 5th ed.; WHO: Geneva, Switzerland; Cambridge University Press: Cambridge, UK, 2010; pp. 4–33. [Google Scholar]
- Kumar, N.; Singh, A.K. Trends of male factor infertility, an important cause of infertility: A review of literature. J. Hum. Reprod. Sci. 2015, 8, 191–196. [Google Scholar] [CrossRef]
- Jeng, H.A.; Huang, Y.-L.; Pan, C.-H.; Norou Diawara, N. Role of low exposure to metals as male reproductive toxicants. Int. J. Environ. Health Res. 2015, 25, 405–417. [Google Scholar] [CrossRef] [Green Version]
- Calogero, A.E.; Fiore, M.; Giacone, F.; Altomare, M.; Asero, P.; Ledda, C.; Romeo, G.; Mongioì, L.M.; Copat, C.; Giuffrida, M.; et al. Exposure to multiple metals/metalloids and human semen quality: A cross-sectional study. Ecotoxicol. Environ. Saf. 2021, 215, 112165. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.X.; Wang, P.; Feng, W.; Liu, C.; Yang, P.; Chen, Y.J.; Sun, L.; Sun, Y.; Yue, J.; Gu, L.J.; et al. Relationships between seminal plasma metals/metalloids and semen quality, sperm apoptosis and DNA integrity. Environ. Pollut. 2017, 224, 224–234. [Google Scholar] [CrossRef]
- Nsonwu-Anyanwu, A.C.; Ekong, E.R.; Offor, S.J.; Awusha, Q.F.; Orji, O.C.; Umoh, E.I.; Owhorji, J.A.; Emetonjor, F.R.; Usoro, C.A.O. Heavy metals, biomarkers of oxidative stress and changes in sperm function: A case-control study. Int. J. Reprod. Biomed. 2019, 17, 163–174. [Google Scholar] [CrossRef]
- Mendiola, J.; Moreno, J.M.; Roca, M.; Vergara-Juárez, N.; Martínez-García, M.J.; García-Sánchez, A.; Elvira-Rendueles, B.; Moreno-Grau, S.; López-Espín, J.J.; Ten, J.; et al. Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: A pilot study. Environ. Health 2011, 10, 6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pant, N.; Kumar, G.; Upadhyay, A.D.; Gupta, Y.K.; Chaturvedi, P.K. Correlation between lead and cadmium concentration and semen quality. Andrologia 2015, 47, 887–891. [Google Scholar] [CrossRef] [PubMed]
- Inoue, K.; Takano, H.; Shimada, A.; Satoh, M. Metallothionein as an anti-inflammatory mediator. Mediators Inflamm. 2009, 101659. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Genchi, G.; Sinicropi, M.S.; Lauria, G.; Carocci, A.; Catalano, A. The Effects of Cadmium Toxicity. Int. J. Environ. Res. Public Health 2020, 17, 3782. [Google Scholar] [CrossRef] [PubMed]
- Sato, S.; Okabe, M.; Kurasaki, M.; Kojima, Y. Metallothionein in the ovaries of laying hens exposed to cadmium. Life Sci. 1996, 58, 1561–1567. [Google Scholar] [CrossRef]
- Foulkes, E.C. Cadmium. In Handbook of Experimental Pharmacology; Springer: Berlin/Heidelberg, Germany, 1986; pp. 1–400. [Google Scholar]
- Jarup, L.; Berglund, M.; Elinder, C.G.; Nordberg, G.; Vahter, M. Health effects of cadmium exposure–A review of the literature and a risk estimate. Scand. J. Work Environ. Health 1998, 24, 1–51. [Google Scholar] [PubMed]
- Prozialeck, W. New insights into the mechanisms of cadmium toxicity–advances in cadmium research. Toxicol. Appl. Pharmacol. 2009, 238, 1–326. [Google Scholar] [CrossRef] [PubMed]
- Moulis, J.-M.; Thevenod, F. New perspectives in cadmium toxicity. BioMetals 2010, 23, 763–960. [Google Scholar] [CrossRef] [Green Version]
- Waalkes, M.P.; Rehm, S.; Peratoni, A. Metal-Binding Proteins of the Syrian Hamster Ovaries: Apparent Deficiency of Metallothionein. Biol. Reprod. 1988, 39, 953–961. [Google Scholar] [CrossRef] [Green Version]
- Rani, A.; Kumar, A.; Lal, A.; Pant, M. Cellular mechanisms of cadmium-induced toxicity: A review. Int. J. Environ. Health Res. 2014, 24, 378–399. [Google Scholar] [CrossRef]
- Satarug, S.; Moore, M.R. Adverse health effects of chronic exposure to low-level cadmium in foodstuffs and cigarette smoke. Environ. Health Perspect. 2004, 112, 1099–1103. [Google Scholar] [CrossRef]
- Satarug, S.; Garrett, S.H.; Somji, S.; Sens, M.A.; Sens, D.A. Zinc, zinc transporters, and cadmium cytotoxicity in a cell culture model of human urothelium. Toxics 2021, 9, 94. [Google Scholar] [CrossRef]
- Satarug, S.; Garrett, S.H.; Somji, S.; Sens, M.A.; Sens, D.A. Aberrant expression of ZIP and ZnT zinc transporters in UROtsa cells transformed to malignant cells by cadmium. Stresses 2021, 1, 78–89. [Google Scholar] [CrossRef]
- Satarug, S.; Vesey, D.A.; Gobe, G.C. The evolving role for zinc and zinc transporters in cadmium tolerance and urothelial cancer. Stresses 2021, 1, 105–118. [Google Scholar] [CrossRef]
- Wang, B.; Schneider, S.N.; Dragin, N.; Girijashanker, K.; Dalton, T.P.; He, L.; Miller, M.L.; Stringer, K.F.; Soleimani, M.; Richardson, D.D.; et al. Enhanced cadmium-induced testicular necrosis and renal proximal tubule damage caused by gene-dose increase in a Slc39a8-transgenic mouse line. Am. J. Physiol. Cell Physiol. 2007, 292, C1523–C1535. [Google Scholar] [CrossRef] [Green Version]
- He, L.; Wang, B.; Hay, E.B.; Nebert, D.W. Discovery of ZIP transporters that participate in cadmium damage to testis and kidney. Toxicol. Appl. Pharmacol. 2009, 238, 250–257. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheng, C.Y.; Mruk, D.D. The blood-testis barrier and its implications for male contraception. Pharmacol. Rev. 2012, 64, 16–64. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol. 2014, 24, R453–R462. [Google Scholar] [CrossRef] [Green Version]
- He, L.; He, T.; Farrar, S.; Ji, L.; Liu, T.; Ma, X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell Physiol. Biochem. 2017, 44, 532–553. [Google Scholar] [CrossRef] [PubMed]
- Tvrdá, E.; Kňažická, Z.; Bárdos, L.; Massányi, P.; Lukáč, N. Impact of oxidative stress on male fertility—A review. Acta Vet. Hung. 2011, 59, 465–484. [Google Scholar] [CrossRef]
- Xu, G.; Liu, S.; Huang, M.; Jiang, X.; Yang, M. Cadmium induces apoptosis of human granulosa cell line KGN via mitochondrial dysfunction-mediated pathways. Ecotoxicol. Environ. Saf. 2021, 220, 112341. [Google Scholar] [CrossRef]
- Nishi, Y.; Yanase, T.; Mu, Y.; Oba, K.; Ichino, I.; Saito, M.; Nomura, M.; Mukasa, C.; Okabe, T.; Goto, K.; et al. Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. Endocrinology 2001, 142, 437–445. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Zou, P.; Zhan, H.; Zhang, M.; Zhang, L.; Ge, R.-S.; Huang, Y. Dihydrolipoamide dehydrogenase and cAMP are associated with cadmium-mediated Leydig cell damage. Toxicol. Lett. 2011, 205, 183–189. [Google Scholar] [CrossRef] [PubMed]
- Ji, X.; Li, Z.; Chen, H.; Li, J.; Tian, H.; Li, Z.; Gao, X.; Xiang, Q.; Su, Z.; Huang, Y.; et al. Cytotoxic mechanism related to dihydrolipoamide dehydrogenase in Leydig cells exposed to heavy metals. Toxicology 2015, 334, 22–32. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.; Guo, X.; Wang, H.; Zhou, S.; Li, L.; Chen, X.; Wang, G.; Liu, J.; Ge, H.-S.; Ge, R.-S. A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis. Sci. Rep. 2017, 207, 6337. [Google Scholar] [CrossRef] [Green Version]
- Zeng, L.; Zhou, J.; Wang, X.; Zhang, Y.; Wang, M.; Su, P. Cadmium attenuates testosterone synthesis by promoting ferroptosis and blocking autophagosome-lysosome fusion. Free Radic. Biol. Med. 2021, 176, 176–188. [Google Scholar] [CrossRef] [PubMed]
- Zhou, G.X.; Zhu, H.L.; Shi, X.T.; Nan, Y.; Liu, W.B.; Dai, L.M.; Xiong, Y.-W.; Yi, S.-J.; Cao, X.-L.; Xu, D.-X.; et al. Autophagy in Sertoli cell protects against environmental cadmium-induced germ cell apoptosis in mouse testes. Environ. Pollut. 2021, 270, 116241. [Google Scholar] [CrossRef] [PubMed]
- Kechiche, S.; Venditti, M.; Knani, L.; Jablonska, K.; Dziegiel, P.; Messaoudi, I.; Reiter, R.J.; Minucci, S. First evidence of the protective role of melatonin in counteracting cadmium toxicity in the rat ovary via the mTOR pathway. Environ. Pollut. 2021, 270, 116056. [Google Scholar] [CrossRef] [PubMed]
- Oyewopo, A.O.; Olaniyi, K.S.; Olojede, S.O.; Lawal, S.K.; Amusa, O.A.; Ajadi, I.O. Hibiscus sabdariffa extract protects against cadmium-induced ovarian toxicity in adult Wistar rats. Int. J. Patophysiol. Pharmacol. 2020, 12, 107–114. [Google Scholar]
- Godam, E.T.; Olaniyan, O.T.; Wofuru, C.D.; Orupabo, C.D.; Ordu, K.S.; Gbaranor, B.K.; Dakoru, P.D. Xylopia aethiopica ethanol seed extract suppresses cadmium chloride-induced ovary and gonadotropins toxicity in adults female Wistar rats. JBRA Assist. Reprod. 2021, 27, 252–256. [Google Scholar] [CrossRef]
- Ruslee, S.S.; Zaid, S.S.; Bakrin, I.H.; Goh, Y.M.; Mustapha, N.M. Protective effect of Tualang honey against cadmium-induced morphological abnormalities and oxidative stress in the ovary of rats. BMC Complement. Med. Ther. 2020, 20, 160. [Google Scholar] [CrossRef] [PubMed]
- Nna, V.U.; Usman, U.Z.; Ofutet, E.O.; Owu, D.U. Quercetin exerts preventive, ameliorative and prophylactic effects on cadmium chloride-induced oxidative stress in the uterus and ovaries of female Wistar rats. Food Chem. Toxicol. 2017, 102, 143–155. [Google Scholar]
- Naď, P.; Massányi, P.; Skalická, M.; Koréneková, B.; Cigánková, V.; Almásiová, V. The effect of cadmium in combination with zinc and selenium on ovarian structure in Japanese quails. J. Environ. Sci. Health A 2007, 42, 2017–2022. [Google Scholar] [CrossRef] [PubMed]
- Paksy, K.; Varga, B.; Lazar, P. Zinc protection against cadmium-induced infertility in female rats. Effect of zinc and cadmium on the progesterone production of cultured granulosa cells. Biometals 1997, 10, 27–36. [Google Scholar] [CrossRef] [PubMed]
- Tirpák, F.; Greifová, H.; Lukáč, N.; Stawarz, R.; Massányi, P. Exogenous Factors Affecting the Functional Integrity of Male Reproduction. Life 2021, 11, 213. [Google Scholar] [CrossRef] [PubMed]
- Mouro, V.G.S.; Martins, A.L.P.; Silva, J.; Menezes, T.P.; Gomes, M.L.M.; Oliveira, J.A.; Melo, F.C.S.A.; Matta, S.L.P. Subacute Testicular Toxicity to Cadmium Exposure Intraperitoneally and Orally. Oxid. Med. Cell. Longev. 2019, 2019, 3429635. [Google Scholar] [CrossRef] [Green Version]
- Wang, H.; Zhang, R.; Song, Y.; Li, T.; Ge, M. Protective Effect of Ganoderma Triterpenoids on Cadmium-Induced Testicular Toxicity in Chickens. Biol. Trace Elem. Res. 2019, 187, 281–290. [Google Scholar] [CrossRef]
- Fan, R.; Hu, P.-C.; Wang, Y.; Lin, H.-Y.; Su, K.; Feng, X.-S.; Wei, L.; Yang, F. Betulinic acid protects mice from cadmium chloride-induced apoptosis in kidney and liver. Toxicol. Lett. 2018, 299, 56–66. [Google Scholar] [CrossRef]
- Babaknejad, N.; Bah&rami, S.; Moshtaghie, S.A.A.; Nayeri, H.; Rajabi, P.; Iranpour, F.G. Cadmium Testicular Toxicity in Male Wistar Rats: Preventive Role of Zinc and Magnesium. Biol. Trace Elem. Res. 2018, 185, 106–115. [Google Scholar] [CrossRef] [PubMed]
- Adamkovičová, M.; Toman, R.; Cabaj, M.; Massányi, P.; Martiniaková, M.; Omelka, R.; Krajčovicová, V.; Ďuránová, H. Effects of Subchronic Exposure to Cadmium and Diazinon on Testis and Epididymis in Rats. Sci. World J. 2014, 2014, 632581. [Google Scholar] [CrossRef] [PubMed] [Green Version]
No. | Foodstuffs | MPC * mg/kg Wet Weight |
---|---|---|
1. | Meat (excluding offal) of bovine animals, sheep, pig, and poultry. | 0.05 |
2. | Horsemeat, excluding offal. | 0.20 |
3. | Liver of bovine animals, sheep, pig, poultry, and horse. | 0.50 |
4. | Kidney of bovine animals, sheep, pig, poultry, and horse. | 1.0 |
5. | Muscle meat of fish, excluding species listed in #6 and #7. | 0.050 |
6. | Bonito (Sarda sarda), common two-banded seabream (Diplodus vulgaris), eel (Anguilla nguilla), grey mullet (Mugil labrosus labrosus), horse mackerel or scad (Trachurus spp), louvar or luvar (Luvarus imperialis), mackerel (Scomber spp), sardine (Sardina pilchardus), sardinops (Sardinops spp), tuna (Thunnus spp, Euthynnus spp, Katsuwonus pelamis), and wedge sole (Dicologoglossa cuneata). | 0.10 |
7. | Muscle meat of bullet tuna (Auxis spp). | 0.20 |
8. | Muscle meat of anchovy (Engraulis spp) and swordfish (Xiphias gladius). | 0.30 |
9. | Crustaceans, excluding brown meat of crab and excluding head and thorax meat of lobster and similar large crustaceans (Nephropidae and Palinuridae). | 0.50 |
10. | Bivalve mollusks. | 1.0 |
11. | Cephalopods (without viscera). | 1.0 |
12. | Cereals, excluding bran, germ, wheat, and rice. | 0.10 |
13. | Bran, germ, wheat, and rice. | 0.20 |
14. | Soybeans. | 0.20 |
15. | Vegetables and fruit, excluding leaf vegetables, fresh herbs, fungi, stem vegetables, root vegetables, and potatoes. | 0.050 |
16. | Stem vegetables, root vegetables and potatoes, excluding celeriac. For potatoes the maximum level applies to peeled potatoes. | 0.10 |
17. | Leaf vegetables, fresh herbs, celeriac, and the following fungi: Agaricus bisporus (common mushroom), Pleurotus ostreatus (Oyster mushroom), Lentinula edodes (Shiitake mushroom). | 0.20 |
18. | Fungi, excluding those listed in #17. | 1.0 |
19. | Food supplements excl. food supplements listed in #20. | 1.0 |
20. | Food supplements consisting exclusively or mainly of dried seaweed or of products derived from seaweed. | 3.0 |
Effects Observed | Study Design/Populations | Risk Estimates |
---|---|---|
Infertility [43]. | NHANES 2013–2016 participants, aged 20–39 years. Data from 42 pregnant and 82 infertile women were analyzed. GM for [Cd]b was 0.26 µg/L. | OR for infertility increased by 1.84-fold per a 2-fold increment of [Cd]b. OR for infertility increased by 1.15- and 2.47-fold, comparing [Cd]b 0.20–0.33 µg/L, 0.34–5.14 µg/L with [Cd]b 0.07–0.19 µg/L. |
Endometriosis [44]. | NHANES 1999–2002 participants (n = 1425) aged 20–49 years. GM for [Cd]b in women with endometriosis was 0.53 µg/L, 20.8% higher than those without endometriosis. | OR for endometriosis increased by 3.39-fold, comparing [Cd]b ≥ 0.5 µg/L) with [Cd]b < 0.3 µg/L after adjusting for age, race/ethnicity, smoking status, use of birth control pills, and exposure to lead and mercury. |
Polycystic ovary syndrome (PCOS) [45]. | A prospective cohort study of 251 healthy women, aged 18–44 years (New York, NY, U.S.). Median [Cd]b was 0.30 µg/L. | The probability of having PCOS was increased by 18% per 0.1 µg/L increment of [Cd]b, together with 2.2%, 2.9% and 7.7% increments of serum concentrations of testosterone, sex hormone-binding globulin and AMH, respectively. PCOS was based on serum AMH and testosterone levels. |
Low ovarian reserve [46]. | NHANES 1988–1994 participants (n = 1681) aged 35–49 years. Additional data from 65 postmenopausal women were analyzed. | RR for low ovarian reserve was increased by 1.4-, 1.6- and 1.8-fold, comparing [Cd]u 0.16–0.38, 0.39–0.77 and > 0.77 µg/L with [Cd]u < 0.16 µg/L, respectively. Low ovarian reserve was defined as [FSH]s ≥ 10 IU/L. |
Ovarian insufficiency [47]. | Chinese women in Zhejiang Province, 169 cases, 209 controls, aged 35–45 years. Median for ECd in cases was 0.58 μg/g creatinine, 25.6% higher than controls. | OR for ovarian insufficiency was increased by 2.5-fold, comparing ECd > 0.68 µg/g creatinine with ECd < 0.37 µg/g creatinine. ECd positively associated with [FSH]s and [LH]s, while showing inverse associations with [AMH]s and [estradiol]s. Ovarian insufficiency was defined as [FSH]s ≥ 25 IU/L. |
Ovarian failure [48]. | Korean women in Soul (n = 283), aged 30–45 years. GM for [Cd]b was 0.97 μg/L. | Ovarian reserve inversely associated with [Cd]b (adjusted β = −0.34, p = 0.02). An inverse association of ovarian reserve and [Cd]b was particularly strong in 30–35-yr age group (adjusted β = −0.43 (p = 0.01). Ovarian reserve was based [AMH]s. |
Effects Observed | Study Design/Populations | Risk Estimates |
---|---|---|
Spermatozoa vitality [51]. | Taiwan, n = 196, mean age 38, 62 (32%) had normal semen quality. Mean for [Cd]u was 0.7 µg/L and mean for ECd was 0.5 μg/g creatinine. | ECd ≥ 0.8 μg/g creatinine were associated in an increased risk of spermatozoa viability decline. Percentages of sperm viability correlated inversely with [Cd]u (r = −0.216) and ECd (r = −0.301). |
Spermatozoa counts, spermatozoa motility/Se as a protective factor [52]. | Italy, n = 179, aged 18–46 years, 131 (73.2%) had two or more at abnormal sperm quality parameters. Seminal plasma Cd was more predictive of semen quality than blood Cd. | In men with abnormal semen quality, the median level for seminal plasma Cd was 2.2-fold higher (0.93 vs. 0.43 μg/L), while the median level for Se was 10.6-fold lower (1.17 vs. 12.36 μg/L), compared to controls. Sperm concentration, total sperm count and progressive motility were increased with increment of seminal plasma Se levels. |
Spermatozoa motility, Zn as a protective factor [53]. | China (Wuhan), n = 746, aged, 18–55 years, 482 (65%) had normal spermatozoa quality, 238, 200, 66, and 56 men were those with low total motility, low spermatozoa progressive motility, low concentration, and low total spermatozoa counts, respectively. | Seminal plasma Cd levels inversely associated with progressive sperm motility and total motility. Seminal plasma Zn levels positively associated with sperm concentrations. Compared with seminal plasma Zn quartile 1, sperm concentrations rose by 13%, 23%, and 25% in seminal plasma Zn quartiles 2, 3 and 4, respectively. |
Spermatozoa concentration [54]. | Nigeria, n = 130, aged 20–60 years, 30, 20 and 50 were azoospermic, oligozoospermic and normozoospermic. | Serum Cd concentrations inversely correlated with sperm concentrations. The means for serum Cd levels in azoospermic and oligospermic were 0.305 and 0.287 µg/L, respectively. These means for serum Cd levels were higher than normospermic group (0.219 µg/L). |
Sperm motility [55]. | Spain, n = 61, age 33.5 ± 3.8 years, 30 infertile cases and 31 controls, The respective GM values for [Cd]b, serum Cd and seminal plasma Cd were 1.0, 0.8, 0.8 μg/L. | Seminal plasma Cd levels positively associated with percentages of immotile sperm after adjustment for age, BMI, and smoking (β = 4.9; 95% CI, 0.84, 9.1). An increment of seminal plasma Cd from 0.7 to 1.0 μg/L was associated with a rise of immotile sperms by 24.3%. |
Sperm motility and concentration [56]. | India (New Delhi), n = 119, aged 20–43 years, 73 infertile cases and 46 controls. | Seminal plasma Cd levels inversely correlated with sperm concentrations (r = −0.33) and sperm motility (r = −0.33). The mean for seminal plasma in cases was 0.591 μg/L, 31.2% higher than controls. The means for seminal plasma Cd were 23.9% and 30.8% higher in men with low sperm concentrations and impaired sperm motility, compared to controls. |
Cadmium Dose/Form/Species | Toxic Signs | Substance | Beneficial Effects | References |
---|---|---|---|---|
50 mg/L as CdCl2 p.o. Wistar rats | Extended estrous cycle; decreased number of primary and antral follicles; larger number of atretic follicles. | Melatonin | Improved estrous cycle duration; improvement in count of primary, secondary, antral and atretic follicles. | Kechiche et al., 2020 [83] |
100 mg/kg b.w. CdCl2 p.o. Wistar rats | Alteration of the cytoarchitecture of the ovaries. | Hibiscus sabdariffa | Restoration of cytoarchitecture; follicle proliferation. | Oyewopo et al., 2020 [84] |
2 mg/kg CdCl2 p.o. Wistar rats | Severe tissue necrosis; follicular cell degeneration, atresia, and no formation of new follicles. | Xylopia aethiopica | Significant improvement of the ovarian histological structure and increment of follicle numbers. | Godam et al., 2020 [85] |
5 mg/kg b.w. CdCl2 p.o. Sprague Dawley rats | Increased number of antral and atretic follicles; morphological abnormalities; decrease in number of follicles. | Tualang honey | Reduced morphological abnormalities in the ovary; restoration of the gonadotropin hormones; reduction in lipid peroxidation levels; increased levels of antioxidant enzymes. | Ruslee et al., 2020 [86] |
5 mg/kg b.w./day CdCl2 p.o. albino Wistar rats | Decrease in viable follicular cells as a result of apoptosis; decreased levels of FSH and LH. | Quercetin | Beneficial effects on the ovaries in cadmium induced toxicity; decrease in apoptosis. | Nna et al., 2017 [87] |
3 mg/kg of feed mixture; 118 days CdCl2 p.o. Japanese quails | Lower relative volume of primary follicles; decrease number of growing follicles; increased relative volume of atretic primary and growing follicles. | Selenium (Na2SeO3) Zinc (ZnSO4) | Se and Zn improved the relative volume of primary and growing follicles. | Naď et al., 2007 [88] |
2.5, 5 and 10 mg/kg b.w. CdCl s.c. CFY rats | Reduced steroidogenesis in cultured granulosa cells; effects on steroid biosynthesis in vitro. | ZnCl2 | Potentiated FSH-stimulated progesterone production. | Paksy et al., 1996 [89] |
Cadmium Dose/Form/Species | Toxic Signs | Substance | Beneficial Effects | References |
---|---|---|---|---|
140 mg/kg CdCl2 p.o. chicken | Deformed seminiferous tubules; mild lesions. | Ganoderma Triterpenoids | Enhanced activity of antioxidant enzymes; reduced MDA content and inflammatory cytokines; reduced damage to testicular morphology. | Wang et al., 2018 [92] |
1 mg/kg CdCl2 i.p. Kunming mice | Pathological lesion in testis; reduced supporting cells and greatly decreased number of spermatozoa in the lumen. | Betulinic acid | Reduced residual levels of cadmium in organs–promotion of cadmium excretion; inhibition of apoptosis. | Fan et al., 2018 [93] |
1 mg/kg b.w./day i.p. Wistar rats | Decrease in spermatozoa count, morphology, motility; degenerative changes in the seminiferous tubule – loss of spermatogenesis; severe necrosis of seminiferous tubules; absence of spermatogenic cells. | ZnCl2, MgCl2 | Spermatozoa observed in seminiferous tubules; lower severity of necrosis; Mg administration significantly reduced Cd effects on spermatozoa quality (at high doses). | Babaknejad et al., 2018 [94] |
30 mg/L; 90 days p.o. Wistar rats | Reduced seminiferous epithelium; decreased tubular lumen; increased vascular surface area and vascular volume. | Diazinon | Combined administration produced fewer pathological alterations in testes than single cadmium administration. | Adamkovicova et al., 2014 [95] |
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Massányi, M.; Satarug, S.; Madeddu, R.; Stawarz, R.; Massányi, P. Evidence for Ovarian and Testicular Toxicities of Cadmium and Detoxification by Natural Substances. Stresses 2022, 2, 1-16. https://doi.org/10.3390/stresses2010001
Massányi M, Satarug S, Madeddu R, Stawarz R, Massányi P. Evidence for Ovarian and Testicular Toxicities of Cadmium and Detoxification by Natural Substances. Stresses. 2022; 2(1):1-16. https://doi.org/10.3390/stresses2010001
Chicago/Turabian StyleMassányi, Martin, Soisungwan Satarug, Roberto Madeddu, Robert Stawarz, and Peter Massányi. 2022. "Evidence for Ovarian and Testicular Toxicities of Cadmium and Detoxification by Natural Substances" Stresses 2, no. 1: 1-16. https://doi.org/10.3390/stresses2010001
APA StyleMassányi, M., Satarug, S., Madeddu, R., Stawarz, R., & Massányi, P. (2022). Evidence for Ovarian and Testicular Toxicities of Cadmium and Detoxification by Natural Substances. Stresses, 2(1), 1-16. https://doi.org/10.3390/stresses2010001