Abstract
Backgrounds
Heavy metals are environmental pollutants and their breakdown is regarded as a serious risk to human health. Despite increasing evidence that heavy metals have adverse effects in vivo and in vitro, there is no evidence of the effect of heavy metals during placental formation.
Objective
We determined the effect of heavy metals on cell viability of BeWo human placental cells using MTS assay and live and dead assay. We also evaluated cell proliferation, cell cycle, and apoptosis by heavy metal treatment using FACS analysis.
Results
Mercury chloride induces severe cell cycle arrest at the sub-G1 phase by the accumulation of cyclin B. Furthermore, we identified that mercury chloride induces apoptosis by enhancing the activity of caspase-3. However, we were unable to confirm the deleterious effect of lead in BeWo cells.
Conclusion
Our results suggested that exposure to heavy metals, specifically mercury chloride, induced cytotoxic effects in BeWo cells through cell cycle arrest and apoptosis.
Similar content being viewed by others
References
Al-Gubory KH (2014) Environmental pollutants and lifestyle factors induce oxidative stress and poor prenatal development. Reprod Biomed Online 29:17–31. https://doi.org/10.1016/j.rbmo.2014.03.002
Barr DB, Bishop A, Needham LL (2007) Concentrations of xenobiotic chemicals in the maternal-fetal unit. Reprod Toxicol 23:260–266. https://doi.org/10.1016/j.reprotox.2007.03.003
Bjorklund G, Dadar M, Mutter J, Aaseth J (2017) The toxicology of mercury: current research and emerging trends. Environ Res 159:545–554. https://doi.org/10.1016/j.envres.2017.08.051
Bommarito PA, Martin E, Fry RC (2017) Effects of prenatal exposure to endocrine disruptors and toxic metals on the fetal epigenome. Epigenomics. https://doi.org/10.2217/epi-2016-0112
Canfield RL et al (2003) Intellectual impairment in children with blood lead concentrations below 10 μg per deciliter. N Engl J Med. https://doi.org/10.1056/NEJMoa022848
Caserta D et al (2013) Heavy metals and placental fetal-maternal barrier. Eur Rev Med Phamacol Sci 17:2198–2206
Chatterjee S, Kundu S, Sengupta S, Bhattacharyya A (2009) Divergence to apoptosis from ROS induced cell cycle arrest: effect of cadmium. Mutat Res 663:22–31. https://doi.org/10.1016/j.mrfmmm.2008.12.011
Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal induced oxidative damage. Curr Top Med Chem. https://doi.org/10.2174/1568026013394831
Flora SJ, Mittal M, Mehta A (2008) Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J Med Res 128:501
Flora G, Gupta D, Tiwari A (2012) Toxicity of lead: a review with recent updates. Interdiscip Toxicol 5:47–58. https://doi.org/10.2478/v10102-012-0009-2
Fonfria E et al (2005) Mercury compounds disrupt neuronal glutamate transport in cultured mouse cerebellar granule cells. J Neurosci Res 79:545–553. https://doi.org/10.1002/jnr.20375
Garza A, Vega R, Soto E (2006) Cellular mechanisms of lead neurotoxicity. Med Sci Monit 12:RA57–RA65
Goyer RA (1990) Transplacental transport of lead. Environ Health Perspect. https://doi.org/10.1289/ehp.9089101
Grandjean P, Landrigan PJ (2006) Developmental neurotoxicity of industrial chemicals. Lancet 368:2167–2178. https://doi.org/10.1016/s0140-6736(06)69665-7
Gundacker C, Hengstschlager M (2012) The role of the placenta in fetal exposure to heavy metals. Wien Med Wochenschr 162:201–206. https://doi.org/10.1007/s10354-012-0074-3
Jang DH, Hoffman RS (2011) Heavy metal chelation in neurotoxic exposures. Neurol Clin 29:607–622. https://doi.org/10.1016/j.ncl.2011.05.002
Jarup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182. https://doi.org/10.1093/bmb/ldg032
Jomova K, Valko M (2011) Advances in metal-induced oxidative stress and human disease. Toxicology 283:65–87. https://doi.org/10.1016/j.tox.2011.03.001
Joshi D et al (2014) N-acetyl cysteine and selenium protects mercuric chloride-induced oxidative stress and antioxidant defense system in liver and kidney of rats: a histopathological approach. J Trace Elem Med Biol 28:218–226. https://doi.org/10.1016/j.jtemb.2013.12.006
Karri V et al (2018) An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line. Toxicol Lett 282:25–36. https://doi.org/10.1016/j.toxlet.2017.10.002
Kil K, Kim M, Kim J, Cho H (2018) Perinatal exposure to di-ethyl-hexyl phthalate via parenteral route induced polycystic ovarian syndrome-like genetic and pathologic changes in F1 offspring mice. Mol Cell Toxicol 15:19–30. https://doi.org/10.1007/s13273-019-0003-2
Kim T, Choi J, Oh S, Choi C (2018a) Effects of waterborne copper on toxicity stress and apoptosis responses in red seabream, Pagrus major. Mol Cell Toxicol 14:201–210. https://doi.org/10.1007/s13273-018-0022-4
Kim W et al (2018b) A study of cytotoxicity and genotoxicity of particulate matter (PM2.5) in human lung epithelial cells (A549). Mol Cell Toxicol 14:163–172. https://doi.org/10.1007/s13273-018-0018-0
Kim K, Kim J, Han J, Moon Y (2019) In vitro estimation of metal-induced disturbance in chicken gut-oviduct chemokine circuit. Mol Cell Toxicol 15:443–452. https://doi.org/10.1007/s13273-019-0048-2
Li A et al (2019) Heavy metals in maternal and cord blood in Beijing and their efficiency of placental transfer. J Environ Sci (China) 80:99–106. https://doi.org/10.1016/j.jes.2018.11.004
Liu B et al (2017) Enhanced oxidative stress by lead toxicity retards cell survival in primary thyroid cells survival in primary thyroid cells. Int J Clin Exp Med 10:4590–4597. https://doi.org/10.1007/s00412-018-0659-8
Lohren H et al (2015) Toxicity of organic and inorganic mercury species in differentiated human neurons and human astrocytes. J Trace Elem Med Biol 32:200–208. https://doi.org/10.1016/j.jtemb.2015.06.008
Mari M et al (2014) Human exposure to metals: levels in autopsy tissues of individuals living near a hazardous waste incinerator. Biol Trace Elem Res 159:15–21. https://doi.org/10.1007/s12011-014-9957-z
Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ (2007) Lead exposure and cardiovascular disease–a systematic review. Environ Health Perspect 115:472–482. https://doi.org/10.1289/ehp.9785
Needham LL et al (2011) Partition of environmental chemicals between maternal and fetal blood and tissues. Environ Sci Technol. https://doi.org/10.1021/es1019614
Omanwar S, Ravi K, Fahim M (2011) Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: mechanisms of endothelial dysfunction. Hum Exp Toxicol 30:1777–1784. https://doi.org/10.1177/0960327110391389
Rice D, Barone S (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect. https://doi.org/10.1289/ehp.00108s3511
Rzymski P et al (2015) Impact of heavy metals on the female reproductive system. Ann Agric Environ Med 22:259–264. https://doi.org/10.5604/12321966.1152077
Silva-Pereira LC et al (2005) Cytotoxicity and genotoxicity of low doses of mercury chloride and methylmercury chloride on human lymphocytes in vitro. Braz J Med Biol Res. https://doi.org/10.1590/s0100-879x2005000600012
Sun X, Kaufman PD (2018) Ki-67: more than a proliferation marker. Chromosoma 127:175–186. https://doi.org/10.1007/s00412-018-0659-8
Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D (2003) Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol 18:149–175. https://doi.org/10.1002/tox.10116
Teixeira FB et al (2018) Exposure to inorganic mercury causes oxidative stress, cell death, and functional deficits in the motor cortex. Front Mol Neurosci 11:125. https://doi.org/10.3389/fnmol.2018.00125
Thompson LA, Darwish WS (2019) Environmental chemical contaminants in food: review of a global problem. J Toxicol 2019:2345283. https://doi.org/10.1155/2019/2345283
Trebucobich MS et al (2014) Protein expression of kidney and liver bilitranslocase in rats exposed to mercuric chloride—a potential tissular biomarker of toxicity. Toxicol Lett 225:305–310. https://doi.org/10.1016/j.toxlet.2013.11.022
Ung CY et al (2010) Mercury-induced hepatotoxicity in zebrafish. BMC Genom. https://doi.org/10.1186/1471-2164-11-212
WHO (2007) Exposure to mercury. World Health Organization (WHO), Genava
WHO (2010) Exposure to lead. World Health Organization (WHO), Genava
Yedjou CG, Tchounwou HM, Tchounwou PB (2016) DNA damage, cell cycle arrest, and apoptosis induction caused by lead in human leukemia cells. Int J Environ Res Public Health 13:ijerph13010056. https://doi.org/10.3390/ijerph13010056
Yoshida M (2002) Placental to fetal transfer of mercury and fetotoxicity. Tohoku J Exp Med. https://doi.org/10.1620/tjem.196.79
Zalups RK (2000) Molecular interactions with mercury in the kidney. Pharmacol Rev 52:113–144
Acknowledgements
The study was supported by Korea Environmental Industry & Technology Institute (KEITI) through “The Environmental Health Action Program” funded by Korea Ministry of Environment (MOE), Grant and Award Number: 2017001360007. This research was also supported by the Chung-Ang University Research Grants in 2018.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Mi Jin Kim, Chul-Hong Kim, Mi-Jin An, Ju-Hyun Lee, Geun-Seup Shin, Hyun-Min Lee, Ji-Young Kim, Jae Yoon Hwang, and Jung-Woong Kim declare that they have no conflict of interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Kim, M.J., Kim, CH., An, MJ. et al. Exposure to mercury induced early apoptotic signals in human placental BeWo cells through alteration of cell cycle regulation. Mol. Cell. Toxicol. 16, 419–429 (2020). https://doi.org/10.1007/s13273-020-00098-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13273-020-00098-2