Reproductive toxicity and associated mechanism of tricresyl phosphate on <i>Caenorhabditis elegans</i>

TANG Jielin; ZHANG Hongdan; ZHOU Qinyu; LI Jiayi; WANG Tong; ZHANG Juan

doi:10.11836/JEOM21396

Volume 39 Issue 5

May 2022

Turn off MathJax

Article Contents

Abstract

References

Journal of Environmental and Occupational Medicine > 2022 > 39(5): 532-538. > DOI: 10.11836/JEOM21396

TANG Jielin, ZHANG Hongdan, ZHOU Qinyu, LI Jiayi, WANG Tong, ZHANG Juan. Reproductive toxicity and associated mechanism of tricresyl phosphate on Caenorhabditis elegans[J]. Journal of Environmental and Occupational Medicine, 2022, 39(5): 532-538. DOI: 10.11836/JEOM21396

Citation:

PDF (1887 KB)

Reproductive toxicity and associated mechanism of tricresyl phosphate on Caenorhabditis elegans

Key Laboratory of Environmental Medicine and Engineering, Ministry of Education/School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China

Funds: This study was funded.

More Information

Corresponding author:
ZHANG Juan,Email:101011288@seu.edu.cn
Received Date: August 28, 2021
Accepted Date: March 27, 2022
Published Date: May 24, 2022

Graphical Abstract

Abstract

Abstract

[Background] Tricresyl phosphate (TCP) is mainly used as a flame retardant. Studies have confirmed that it has cytotoxicity and neurotoxicity, but its reproductive toxicity is not clear.

[Objective] To investigate the reproductive toxicity and potential mechanism of TCP subacute exposure on Caenorhabditis elegans.

[Methods] Caenorhabditis elegans were exposed to solvent control and 0.1, 1, 10, 100, and 1000 μg·L⁻¹ TCP respectively for 72 h. Brood size and number of fertilized eggs in the uterus were detected to evaluate reproductive ability. The number of total germline cells and the relative area of gonad arm were measured to evaluate the development of gonads. The body length and body width of Caenorhabditis elegans were detected to evaluate growth and development. The activities of reactive oxygen species (ROS) and superoxide dismutase (SOD) in Caenorhabditis elegans, and the mitochondrial active oxygen metabolism genes (mev-1 and gas-1) of N2 nematodes were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) to evaluate oxidative stress. WS1433 transgenic nematodes and wild-type nematodes N2 were exposed to solvent control or TCP (0.1, 1, 10, 100, and 1000 μg·L⁻¹) respectively. DNA damage in germ cells of WS1433 transgenic nematodes was detected, the relative expressions of DNA damage-related genes (hus-1, clk-2, cep-1, and egl-1) in N2 nematodes were detected by qRT-PCR to evaluate the effect of TCP exposure on genetic damage.

[Results] Compared with the solvent control group (217.00 ± 12.20), the brood size of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (170.80 ± 11.51, 169.60 ± 10.52, P < 0.05). Compared with the solvent control group (18.43 ± 1.69), the number of fertilized eggs of N2 nematodes in the 100 μg·L ⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (13.47 ± 0.81, 11.95 ± 0.90,P < 0.05). Compared with the solvent control group (312.46 ± 77.4), the number of total germline cells of N2 nematodes in the 100 μg·L ⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (281.80 ± 12.98, 273.50 ± 8.53,P < 0.05). Compared with the solvent control group, the relative area of gonads of N2 nematodes in the 100 μg·L ⁻¹ and 1000 μg·L⁻¹ TCP groups decreased by 13.83% and 17.25% respectively (P<0.05). Compared with the solvent control group [(1058.10±80.12) μm, (78.21±14.69) μm], the body length and body width of N2 nematodes in the 100 μg·L⁻¹ and 1000 μg·L⁻¹ TCP groups decreased (P<0.05). Compared with the solvent control group, the relative fluorescence intensity of ROS in nematodes in the 10, 100, and 1000 μg·L⁻¹ TCP groups increased significantly (107.60%±1.02%, 105.90%±1.40%, and 106.40%±1.85%, respectively, P<0.05), and the activities of SOD were reduced (by 20.66%, 15.88%, and 16.44%, respectively,P<0.05). Compared with the solvent control group (1.3±1.3), the number of DNA-damaged germ cells of WS1433 nematodes in the 100 and 1000 μg·L⁻¹ TCP groups increased significantly (2.4±0.3, 2.7±0.3, P<0.05); the expressions ofmev-1 andgas-1 genes in N2 nematodes in the 10, 100 and 1000 μg·L⁻¹ TCP groups decreased significantly (P<0.05); the expressions ofhus-1 in the 0.1-1000 μg·L⁻¹ TCP groups significantly increased (P<0.05); the expressions ofclk-2 and egl-1 in the 100 and 1000 μg·L⁻¹ TCP groups increased significantly (P<0.05); the expressions ofcep-1 in the 1, 10, and 100 μg·L⁻¹ TCP groups increased significantly (P<0.05).

[Conclusion] TCP may cause reproductive damage to nematodes through oxidative stress and germ cell DNA damage.
- organophosphate esters,
- Caenorhabditis elegans,
- reproductive toxicity,
- DNA damage,
- oxidative stress

FullText(HTML)

References (34)

References

[1]	VAN DER VEEN I, DE BOER J. Phosphorus flame retardants: Properties, production, environmental occurrence, toxicity and analysis[J]. Chemosphere, 2012, 88(10): 1119-1153. doi: 10.1016/j.chemosphere.2012.03.067
[2]	DING J, XU Z, HUANG W, et al. Organophosphate ester flame retardants and plasticizers in human placenta in Eastern China[J]. Sci Total Environ, 2016, 554-555: 211-217. doi: 10.1016/j.scitotenv.2016.02.171
[3]	FENG L, OUYANG F, LIU L, et al. Levels of urinary metabolites of organophosphate flame retardants, TDCIPP, and TPHP, in pregnant women in Shanghai[J]. J Environ Public Health, 2016, 2016: 9416054.
[4]	MA Y, JIN J, LI P, et al. Organophosphate ester flame retardant concentrations and distributions in serum from inhabitants of Shandong, China, and changes between 2011 and 2015[J]. Environ Toxicol Chem, 2017, 36(2): 414-421. doi: 10.1002/etc.3554
[5]	SUNDKVIST A M, OLOFSSON U, HAGLUND P. Organophosphorus flame retardants and plasticizers in marine and fresh water biota and in human milk[J]. J Environ Monit, 2010, 12(4): 943-951. doi: 10.1039/b921910b
[6]	HOU R, XU Y, WANG Z. Review of OPFRs in animals and humans: absorption, bioaccumulation, metabolism, and internal exposure research[J]. Chemosphere, 2016, 153: 78-90. doi: 10.1016/j.chemosphere.2016.03.003
[7]	XU Q, WU D, DANG Y, et al. Reproduction impairment and endocrine disruption in adult zebrafish (Danio rerio) after waterborne exposure to TBOEP[J]. Aquat Toxicol, 2017, 182: 163-171. doi: 10.1016/j.aquatox.2016.11.019
[8]	LI H, YUAN S, SU G, et al. Whole-life-stage characterization in the basic biology of Daphnia magna and effects of TDCIPP on growth, reproduction, survival, and transcription of genes[J]. Environ Sci Technol, 2017, 51(23): 13967-13975. doi: 10.1021/acs.est.7b04569
[9]	ZHANG X, TANG X, YANG Y, et al. Responses of the reproduction, population growth and metabolome of the marine rotifer Brachionus plicatilis to tributyl phosphate (TnBP)[J]. Environ Pollut, 2021, 273: 116462. doi: 10.1016/j.envpol.2021.116462
[10]	BOLON B, BUCCI T J, WARBRITTON A R, et al. Differential follicle counts as a screen for chemically induced ovarian toxicity in mice: results from continuous breeding bioassays[J]. Fundam Appl Toxicol, 1997, 39(1): 1-10. doi: 10.1006/faat.1997.2338
[11]	CARIGNAN C C, MÍNGUEZ-ALARCÓN L, BUTT C M, et al. Urinary concentrations of organophosphate flame retardant metabolites and pregnancy outcomes among women undergoing in vitro fertilization[J]. Environ Health Perspect, 2017, 125(8): 087018. doi: 10.1289/EHP1021
[12]	CHEN J X, XU L L, MEI J H, et al. Involvement of neuropathy target esterase in tri-ortho-cresyl phosphate-induced testicular spermatogenesis failure and growth inhibition of spermatogonial stem cells in mice[J]. Toxicol Lett, 2012, 211(1): 54-61. doi: 10.1016/j.toxlet.2012.03.004
[13]	LIU X, XU L, SHEN J, et al. Involvement of oxidative stress in tri-ortho-cresyl phosphate-induced autophagy of mouse Leydig TM3 cells in vitro[J]. Reprod Biol Endocrinol, 2016, 14(1): 30. doi: 10.1186/s12958-016-0165-x
[14]	WANG J, RUAN W, HUANG B, et al. Tri-ortho-cresyl phosphate induces autophagy of mouse ovarian granulosa cells[J]. Reproduction, 2019, 158(1): 61-69. doi: 10.1530/REP-18-0456
[15]	CHEN G, ZHANG S, JIN Y, et al. TPP and TCEP induce oxidative stress and alter steroidogenesis in TM3 Leydig cells[J]. Reprod Toxicol, 2015, 57: 100-110. doi: 10.1016/j.reprotox.2015.05.011
[16]	DISHAW L V, POWERS C M, RYDE I T, et al. Is the PentaBDE replacement, tris (1, 3-dichloro-2-propyl) phosphate (TDCPP), a developmental neurotoxicant? Studies in PC12 cells[J]. Toxicol Appl Pharmacol, 2011, 256(3): 281-289. doi: 10.1016/j.taap.2011.01.005
[17]	BANERJEE B D, SETH V, AHMED R S. Pesticide-induced oxidative stress: perspective and trends[J]. Rev Environ Health, 2001, 16(1): 1-40. doi: 10.1515/REVEH.2001.16.1.1
[18]	INGLE M E, WATKINS D, ROSARIO Z, et al. An exploratory analysis of urinary organophosphate ester metabolites and oxidative stress among pregnant women in Puerto Rico[J]. Sci Total Environ, 2020, 703: 134798. doi: 10.1016/j.scitotenv.2019.134798
[19]	BAMAI Y A, BASTIAENSEN M, ARAKI A, et al. Multiple exposures to organophosphate flame retardants alter urinary oxidative stress biomarkers among children: the Hokkaido study[J]. Environ Int, 2019, 131: 105003. doi: 10.1016/j.envint.2019.105003
[20]	LU S Y, LI Y X, ZHANG T, et al. Effect of E-waste recycling on urinary metabolites of organophosphate flame retardants and plasticizers and their association with oxidative stress[J]. Environ Sci Technol, 2017, 51(4): 2427-2437. doi: 10.1021/acs.est.6b05462
[21]	BEHL M, HSIEH J H, SHAFER T J, et al. Use of alternative assays to identify and prioritize organophosphorus flame retardants for potential developmental and neurotoxicity[J]. Neurotoxicol Teratol, 2015, 52: 181-193. doi: 10.1016/j.ntt.2015.09.003
[22]	BEHL M, RICE J R, SMITH M V, et al. Editor’s highlight: comparative toxicity of organophosphate flame retardants and polybrominated diphenyl ethers to Caenorhabditis elegans[J]. Toxicol Sci, 2016, 154(2): 241-252. doi: 10.1093/toxsci/kfw162
[23]	徐诚, 宋宁慧, 张圣虎, 等. 长江南京段水体及市政自来水中多种OPEs的分布特征[J]. 环境监测管理与技术, 2018, 30(4): 60-64. doi: 10.3969/j.issn.1006-2009.2018.04.015 XU C, SONG N H, ZHANG S H, et al. Distribution of organophosphates in Yangtze River and running water in Nanjing[J]. Administration and Technique of Environmental Monitoring, 2018, 30(4): 60-64. doi: 10.3969/j.issn.1006-2009.2018.04.015
[24]	WANG T, XU C, SONG N, et al. Seasonal variation and health risk assessment of organophosphate esters in surface and drinking water in Nanjing, China [J]. Int J Environ Sci Technol, 2022: doi.org/10.1007/s13762-022-03987-2.
[25]	DAYEM A A, HOSSAIN M K, LEE S B, et al. The role of reactive oxygen species (ROS) in the biological activities of metallic nanoparticles[J]. Int J Mol Sci, 2017, 18(1): 120. doi: 10.3390/ijms18010120
[26]	VALKO M, LEIBFRITZ D, MONCOL J. Free radicals and antioxidants in normal physiological functions and human disease[J]. Int J Biochem Cell Biol, 2007, 39(1): 44-84. doi: 10.1016/j.biocel.2006.07.001
[27]	ZHAO L, RUI Q, WANG D. Molecular basis for oxidative stress induced by simulated microgravity in nematode Caenorhabditis elegans[J]. Sci Total Environ, 2017, 607-608: 1381-1390. doi: 10.1016/j.scitotenv.2017.07.088
[28]	ISHII T, MIYAZAWA M, ONOUCHI H, et al. Model animals for the study of oxidative stress from complex II[J]. Biochim Biophys Acta, 2013, 1827(5): 588-597. doi: 10.1016/j.bbabio.2012.10.016
[29]	ZHANG H, LIU T, SONG X, et al. Study on the reproductive toxicity and mechanism of tri-n-butyl phosphate (TnBP) in Caenorhabditis elegans[J]. Ecotoxicol Environ Saf, 2021, 227: 112896. doi: 10.1016/j.ecoenv.2021.112896
[30]	HOFMANN E R, MILSTEIN S, BOULTON S J, et al. Caenorhabditis elegans HUS-1 is a DNA damage checkpoint protein required for genome stability and EGL-1-mediated apoptosis[J]. Curr Biol, 2002, 12(22): 1908-1918. doi: 10.1016/S0960-9822(02)01262-9
[31]	AHMED S, ALPI A, HENGARTNER M O, et al. C. elegans RAD-5/CLK-2 defines a new DNA damage checkpoint protein[J]. Curr Biol, 2001, 11(24): 1934-44. doi: 10.1016/S0960-9822(01)00604-2
[32]	POLLI J R, ZHANG Y, PAN X. Dispersed crude oil amplifies germ cell apoptosis in Caenorhabditis elegans, followed a CEP-1-dependent pathway[J]. Arch Toxicol, 2014, 88(3): 543-551.
[33]	NEHME R, CONRADT B. egl-1: a key activator of apoptotic cell death in C. elegans [J]. Oncogene, 2008, 27 (Suppl 1): S30-40.
[34]	AL-SALEM A M, SAQUIB Q, SIDDIQUI M A, et al. Organophosphorus flame retardant (tricresyl phosphate) trigger apoptosis in HepG2 cells: Transcriptomic evidence on activation of human cancer pathways[J]. Chemosphere, 2019, 237: 124519. doi: 10.1016/j.chemosphere.2019.124519