Peculiarities of cadmium accumulation in the gonads in heterosexual laboratory animals

Introduction. The present study examined the bioaccumulation of cadmium in the gonads in heterosexual rats and assessed the effects of low doses of cadmium on the level of essential elements during subchronic intoxication by oral route. Our results showed cadmium to accumulate in both female and male reproductive organs, regardless of exposure dose, and also affects the calcium, zinc, and copper content in the gonads in animals.
Materials and methods. Three groups of different-sex white outbred rats were intragastrically injected with a cadmium chloride solution containing 1 (Cd1), 10 (Cd10) and 100 (Cd100) μg of cadmium per kg of body weight daily for 3 months. Cadmium exposure was assessed after 1, 4, 12, 30, 60, and 90 days. Concentrations of cadmium, calcium, copper, and zinc in the gonads were measured by atomic absorption spectrometry.
Results. After 1 day, a sharp increase in cadmium concentration was observed in all groups. The content exceeded the control up to 60 times. After 4 days, cadmium levels in all groups decreased to 0.02 mg/kg and remained approximately at the same level until 30 days. An increase in cadmium concentration was detected in the testes at the beginning of the experiment, then a smooth decrease was observed, but by the end of the study the cadmium concentration remained higher than in the control group. The copper content in the ovaries of females did not change, while in males an increase by 1.7 times was detected in all groups. The calcium concentration in the ovaries of females was by 1.4–1.6 times higher than that in controls; in males, on the contrary, a trend towards to a decrease in calcium was established. The zinc content in the ovaries of females did not change regardless of the dose of cadmium; a slight increase was observed in the organs of males.
Limitations. The assessment of cadmium accumulation in the gonads of heterosexual animals was carried out without studying reprotoxicity and pathomorphology.
Conclusion. In the present study, marked changes in the concentration of essential elements in the gonads of laboratory animals were observed, which may be an indicator of disruption of cellular homeostasis. The gonads of females were revealed to be more susceptible to cadmium, since the content of this element was higher than in the gonads of males.

cadmium, rats, animal gonads, essential elements

1. Zou M., Zhou S., Zhou Y., Jia Z., Guo T., Wang J. Cadmium pollution of soil-rice ecosystems in rice cultivation dominated regions in China: A review. Environ. Pollut. 2021; 280: 116965. https://doi.org/10.1016/j.envpol.2021.116965

2. Satarug S. Dietary cadmium intake and its effects on kidneys. Toxics. 2018; 6(1): 15. https://doi.org/10.3390/toxics6010015

3. Rzymski P., Niedzielski P., Rzymski P., Tomczyk K., Kozak L., Poniedziałek B. Metal accumulation in the human uterus varies by pathology and smoking status. Fertil. Steril. 2016; 105(6): 1511–8.e3. https://doi.org/10.1016/j.fertnstert.2016.02.006

4. Nordberg G.F., Bernard A., Diamond G.L., Duffus J.H., Illing P., Nordberg M., et al. Risk assessment of effects of cadmium on human health (IUPAC Technical Report). Pure Appl. Chem. 2018; 90(4): 755–808. https://doi.org/10.1515/pac-2016-0910

5. Farimani Raad H., Pardakhti A., Kalarestaghi H. Carcinogenic and non-carcinogenic health risk assessment of heavy metals in ground drinking water wells of Bandar Abbas. Pollution. 2021; 7(2): 395–404.

6. Andjelkovic M., Buha Djordjevic A., Antonijevic E., Antonijevic B., Stanic M., Kotur-Stevuljevic J., et al. Toxic effect of acute cadmium and lead exposure in rat blood, liver, and kidney. Int. J. Environ. Res. Public Health. 2019; 16(2): 274. https://doi.org/10.3390/ijerph16020274

7. Egger A.E., Grabmann G., Gollmann-Tepeköylü C., Pechriggl E.J., Artner C., Türkcan A., et al. Chemical imaging and assessment of cadmium distribution in the human body. Metallomics. 2019; 11(12): 2010–9. https://doi.org/10.1039/c9mt00178f

8. Monsefi M., Fereydouni B. The effects of cadmium pollution on female rat reproductive system. J. Infertil. Reprod. Biol. 2013; 1(1): 1–6.

9. Satarug S., Gobe G.C., Ujjin P., Vesey D.A. A comparison of the nephrotoxicity of low doses of cadmium and lead. Toxics. 2020; 8(1): 18. https://doi.org/10.3390/toxics8010018

10. Wu X., Guo X., Wang H., Zhou S., Li L., Chen X., et al. A brief exposure to cadmium impairs Leydig cell regeneration in the adult rat testis. Sci. Rep. 2017; 7(1): 6337. https://doi.org/10.1038/s41598-017-06870-0

11. Santana V.P., Salles É.S., Correa D.E., Gonçalves B.F., Campos S.G., Justulin L.A., et al. Long-term effects of perinatal exposure to low doses of cadmium on the prostate of adult male rats. Int. J. Exp. Pathol. 2016; 97(4): 310–6. https://doi.org/10.1111/iep.12193

12. Ali W., Ma Y., Zhu J., Zou H., Liu Z. Mechanisms of cadmium-induced testicular injury: a risk to male fertility. Cells. 2022; 11(22): 3601. https://doi.org/10.3390/cells11223601

13. Kumar S., Sharma A. Cadmium toxicity: effects on human reproduction and fertility. Rev. Environ. Health. 2019; 34(4): 327–38. https://doi.org/10.1515/reveh-2019-0016

14. de Souza Predes F., Diamante M.A., Dolder H. Testis response to low doses of cadmium in Wistar rats. Int. J. Exp. Pathol. 2010; 91(2): 125–31. https://doi.org/10.1111/j.1365-2613.2009.00692.x

15. Xu L.C., Sun H., Wang S.Y., Song L., Chang H.C., Wang X.R. The roles of metallothionein on cadmium-induced testes damages in Sprague-Dawley rats. Environ. Toxicol. Pharmacol. 2005; 20(1): 83–7. https://doi.org/10.1016/j.etap.2004.10.008

16. Зиатдинова М.М., Валова Я.В., Мухаммадиева Г.Ф., Фазлыева А.С., Каримов Д.О., Хуснутдинова Н.Ю. Оценка активности генов МТ2А и МТ3 в печени и почках крыс в ответ на введение разных доз хлорида кадмия. Медицина труда и экология человека. 2021; (1): 93–101. https://doi.org/10.24412/2411-3794-2021-10109 https://elibrary.ru/lcamjh

17. Cuypers A., Plusquin M., Remans T., Jozefczak M., Keunen E., Gielen H., et al. Cadmium stress: an oxidative challenge. Biometals. 2010; 23(5): 927–40. https://doi.org/10.1007/s10534-010-9329-x

18. Halliwell B., Gutteridge J.M. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol. 1990; 186: 1–85. https://doi.org/10.1016/0076-6879(90)86093-b

19. Uetani M., Kobayashi E., Suwazono Y., Kido T., Nogawa K. Cadmium exposure aggravates mortality more in women than in men. Int. J. Environ. Health Res. 2006; 16(4): 273–9. https://doi.org/10.1080/09603120600734220

20. Nasiadek M., Krawczyk T., Sapota A. Tissue levels of cadmium and trace elements in patients with myoma and uterine cancer. Hum. Exp. Toxicol. 2005; 24(12): 623–30. https://doi.org/10.1191/0960327105ht575oa

21. Nasiadek M., Danilewicz M., Klimczak M., Stragierowicz J., Kilanowicz A. Subchronic exposure to cadmium causes persistent changes in the reproductive system in female Wistar rats. Oxid. Med. Cell. Longev. 2019; 2019: 6490820. https://doi.org/10.1155/2019/6490820

22. Bhardwaj J.K., Panchal H., Saraf P. Cadmium as a testicular toxicant: a review. J. Appl. Toxicol. 2021; 41(1): 105–17. https://doi.org/10.1002/jat.4055