The effect of sublethal doses of cadmium chloride on the development of preimplantation embryos of mice in two generations

Original article

УДК 616.13.002.2
DOI: 10.57034/2618723X-2024-01-03

E.M. Noniashvili*,
PhD of biological sciences, Senior Researcher,
https://orcid.org/0000-0002-2347-6920
I.O. Suchkova,
PhD of biological sciences, Senior Researcher,
https://orcid.org/0000-0003-2127-0459
E.L. Patkin,
MD of biological sciences, Head of Laboratory,
https://orcid.org/0000-0002-6292-4167

FSBSI “Institute of Experimental Medicine”,
Russia, 197022, St Petersburg, akad. Pavlova str. 12.

*E-mail: [email protected]


Keywords: cadmium chloride preimplantation mouse embryos morula blastocysts blastomere transgenerational effect of cadmium chloride

Acknowledgements

The work was carried out within the framework of the state assignment of the Ministry of Science and Higher Education of the Russian Federation: research work No. FGWG-2022-0012 (registration No. NIOKTR 122020300196-4).


For citation:

Noniashvili E.M., Suchkova I.O., Patkin E.L. The effect of sublethal doses of cadmium chloride on the development of preimplantation embryos of mice in two generations. Laboratory Animals for Science. 2024; 1. https://doi.org/10.57034/2618723X-2024-01-03

Abstract

Cadmium is a heavy metal, highly toxic pollutant, entering the environment as a by-product of most modern industries. The effect of cadmium on the body depends on the route of entry, duration and dose of exposure. One of the important areas of this research is the study of the effect of cadmium on early development, leading to diseases in the adult body and possible developmental abnormalities in offspring. The aim of this study was to analyze the development of preimplantation embryos of mice exposed in utero to cadmium chloride and embryos obtained from cadmium-exposed parents. Preimplantation embryos of F1 (CBA×C57BL) hybrid mice exposed in utero to 30 µM of cadmium chloride (F1 — the first generation) and embryos of similar age, obtained from females and males, exposed in utero (F2 — the second generation), was studied. The toxic effect of cadmium chloride was studied by paternal, maternal and “double” (both parents were exposed) lines of inheritance. The development of embryos was assessed by the rate of blastomeres cleavage and the number of blastocysts. The F1 generation embryos exposed to cadmium chloride in utero passed the initial stages of cleavage and blastocyst formation faster compared to the control embryos. The development of the the maternal line second generation embryos (F2) was comparable with the control group. In the paternal and “double” (both parents were exposed) lines of inheritance, the rate of cleavage at the morula stage was slowdown, however, at the blastocyst stage, the rate of cleavage of embryos did not statistically differ from the control embryos. The effect of sublethal doses of cadmium chloride on famale mice at the onset of pregnancy affects not only the embryos of the first generation, directly exposed to cadmium chloride, but also the descendants of exposed parents in the second generation, slowing down the process of proliferation in the embryos of the paternal line of inheritance and in embryos born from two exposed parents. The results obtained in our model suggest that the harm from smoking caused by the accumulation of cadmium is manifested not only in children, but also in grandchildren. The epigenetic mechanism of such inheritance is most likely, which gives grounds for the development of preventive approaches to eliminate possible harmful consequences. It is advisable to recommend stopping smoking during pregnancy and in the period before conception.

Conflict of interest

The authors declare no conflict of interest.

Authors contribution

All authors made significant contributions to the concept and preparation of the article and approved the final version before publication.
E.M. Noniashvili — planning and conducting experiments, writing the manuscript.
I.O. Suchkova — statistical analysis, table creation.
E.L. Patkin — study design, manuscript editing.

References

  1. Saturg S., Moore M. Adverse Health Effects of Chronic Exposure to Low-Level Cadmium in Foodstoffs and Cigarette Smoke // Environmental Health Perspectives. 2004. Vol. 112. N. 10. P. 1099–1103. DOI: 10.1289/ehp.6751.
  2. Nishijo M., Satarug S., Honda R., Tsuritani I., Aoshima R. The gender differences in health effects of environmental cadmium exposure and potential mechanisms // Mol. Cell. Biochem. 2004. N. 255. P. 87–92. DOI: 10.1023/b:mcbi.0000007264.37170.39.
  3. Mortada W.I., Sobh M.A., El-Defrawy M.M. The exposure to cadmium, lead and mercury from smoking and its impact on renal integrity // Med. Sci. Monit. 2004. Vol. 10. N. 3. P. 112–116.
  4. Ionheimo H., Lange R., Tolonen H., Kolossa-Gehring M. Exposure to toxic metals and per- and polyfluoroalkyl substances and the risk of preeclampsia and preterm birth in the United States: a review // J. Obstet. Gynecol MFM. 2021. Vol. 3. N. 3. P. 100–308.
  5. Llanos M.N., Ronco A.M. Fetal growth restriction is related to placental levels of cadmium, lead and arsenic but not with antioxidant activities // Reprod. Toxicol. 2009. Vol. 27. N. 1. P. 88–92. DOI: 10.1016/j.reprotox.2008.11.057.
  6. Piasek M., Micolic A., Sekovanic A., Grgec A., Jurasovic A.S. Cadmium in placenta — a valuable biomarker of exposure during pregnancy in biomedical research // J. Toxocol. Environ. Health. 2014. Vol. 77. N. 18. P. 1071–1074. DOI: 10.1080/15287394.2014.915779.0.
  7. Нониашвили Е.М. Развитие доимплантационных зародышей мышей в условиях воздействия сублетальных доз хлорида кадмия на материнский организм // Токсикологический вестник. 2023. № 4 (31). С. 232–236. [Noniashvili E.M. Razvitie doimplantacionny’x zarody’shej my’shej v usloviyax vozdejstviya subletal’ny’x doz xlorida kadmiya na materinskij organism // Toksikologicheskij vestnik. 2023. N. 4 (31). P. 232–236. (In Russ.)].
  8. Barker D.J., Clark P. M. Fetal under nutrition and dise­ase in later life // Rev. Reprod. 1997. N. 2. P. 105–112. DOI: 10.1530/ror.0.0020105.
  9. Barker D., Eriksson J., Forsen T., Osmond C. Fetal origins of adult disease: Strength of effects and biological basis // Int. J. Epidemiol. 2002. N. 31. P. 1235–1239. DOI: 10.1093/ije/31.6.1235.
  10. Нониашвили Е.М., Чан В.Ч., Грудинина Н.А., Софронов Г.А., Епринцев А.Т., Паткин Е.Л. Особенности развития доимплантационных зародышей мышей в присутствии малых доз хлористого кадмия in vitro // Вестник Воронежского гос. университета. Серия: Химия. Биология. Фармация. 2019. № 1. С. 48–55. [Noniashvil E.M., Chan V.Ch., Grudinina N. A., Sofronov G.A., Eprincev A.T., Patkin E.L. Osobennosti razvitiya doimplantacionny’x zarody’shej my’shej v prisutstvii maly’x doz xloristogo kadmiya in vitro // Vestnik Voronejskogo gos. Universiteta. Seria: Chimia, Biologia, Pharmacia. 2019. N. 1. P. 48–55. (In Russ.)].
  11. Dalton T., Fu K., Enders G.C., Palmiter R.D., Andrews G.K. Analysis of the effects of overexpression of metallothionein-1 in transgenic mice on the reproductive toxicology of cadmium // Environmental Health Perspectives. 1996. 1041. P. 68–76. DOI: 10.1289/ehp.9610468.
  12. Shiverick K.T., Salafia C. Cigarette smoking and pregnancy I: Ovarian, uterine and placental effects // Placenta. 1999. Vol. 20. P. 65–72.
  13. Fang M.Z., Mar W.C., Cho M.H. Cadmium-induced alte­rations of connexin expression in the promotion stage of in vitro two-stage transformation // Toxicology. 2001. Vol. 161. N. 1–2. P. 117–127. DOI: 10.1016/s0300-483x(01)00344-4.
  14. Thompson J., Bannigan J. Cadmium: Toxic effects on the reproductive system and the embryo // Reprod. Toxicol. 2008. Vol. 25. P. 304–315. DOI: 10.1016/j.reprotox.2008.02.001.
  15. Maes M., Vinken M. Connexin-based signaling and drug-induced hepatotoxicity // Clin. Trans. Res. 2017. Vol. 3. N. 1. P. 189–198. DOI: 10.18053/jctres.03.2017S1.004.

Received: 2023-09-25
Reviewed: 2023-11-30
Accepted for publication: 2024-02-05

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