Progress in Evaluating Embryotoxicity of Compounds Based on Human Embryonic Stem Cell Model in Vitro

doi:10.12280/gjfckx.20240854

Abstract

Abstract:

Embryonic stem cell test (EST) was widely used in evaluation of embryotoxicity or developmental toxicity of compounds in the fields of drugs, chemicals, and environmental safety. In recent years. Compared to the traditional reproductive toxicity tests, EST has the advantages of short cycletime, high throughput and low loss, in order to further improve the applicability and safety assessment of EST to various drugs and to avoid species differences, researchers used human embryonic stem cell (hESC) instead of the original mouse embryonic stem cell (mESC), and the researches which utilized hESC to evaluate embryotoxicity or developmental toxicity have been became more diversified and in-depth, such as the development of different evaluation models of differentiation types (myocardial cell, nerve cell and osteoblast etc.) or the construction of three-dimensional (3D) models which were closer to real living condition of embryo (embryoid bodys and organoid), these studies provided a new direction for establishing a more accurate and efficient model for the evaluation of embryotoxicity.

Key words: Human embryonic stem cells, Embryo, mammalian, Models, theoretical, Cells, cultured, In vitro techniques, Embryotoxicity

SUN Lu, CHEN Ran-ran, SONG Dian-rong. Progress in Evaluating Embryotoxicity of Compounds Based on Human Embryonic Stem Cell Model in Vitro[J]. Journal of International Obstetrics and Gynecology, 2024, 51(6): 707-711.

References 28

[1]	Spielmann H, Pohl I, Döring B, et al. The embryonic stem cell test (EST), an in vitro embryotoxicity test using two permanent mouse cell lines: 3T3 fibroblasts and embryonic stem cells[J]. In Vitro Toxicol, 1997, 10(1):119-127. doi: 10.1007/978-3-7091-7500-2_69.
[2]	Mennen RH, Oldenburger MM, Piersma AH. Endoderm and mesoderm derivatives in embryonic stem cell differentiation and their use in developmental toxicity testing[J]. Reprod Toxicol, 2022, 107:44-59. doi: 10.1016/j.reprotox.2021.11.009.
[3]	Adler S, Pellizzer C, Hareng L, et al. First steps in establishing a developmental toxicity test method based on human embryonic stem cells[J]. Toxicol In Vitro, 2008, 22(1):200-211. doi: 10.1016/j.tiv.2007.07.013. pmid: 17961973
[4]	Klemm M, Schrattenholz A. Neurotoxicity of active compounds--establishment of hESC-lines and proteomics technologies for human embryo- and neurotoxicity screening and biomarker identification[J]. ALTEX, 2004, 21(Suppl 3):41-48.
[5]	Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts[J]. Science, 1998, 282(5391):1145-1147. doi: 10.1126/science.282.5391.1145. pmid: 9804556
[6]	Richards M, Fong CY, Chan WK, et al. Human feeders support prolonged undifferentiated growth of human inner cell masses and embryonic stem cells[J]. Nat Biotechnol, 2002, 20(9):933-936. doi: 10.1038/nbt726. pmid: 12161760
[7]	Shewale B, Dubois N. Of form and function: Early cardiac morphogenesis across classical and emerging model systems[J]. Semin Cell Dev Biol, 2021, 118:107-118. doi: 10.1016/j.semcdb.2021.04.025. pmid: 33994301
[8]	Braam SR, Tertoolen L, van de Stolpe A, et al. Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes[J]. Stem Cell Res, 2010, 4(2):107-116. doi: 10.1016/j.scr.2009.11.004. pmid: 20034863
[9]	Jiang Y, Wang D, Zhang G, et al. Disruption of cardiogenesis in human embryonic stem cells exposed to trichloroethylene[J]. Environ Toxicol, 2016, 31(11):1372-1380. doi: 10.1002/tox.22142. pmid: 25847060
[10]	Fu H, Wang L, Wang J, et al. Dioxin and AHR impairs mesoderm gene expression and cardiac differentiation in human embryonic stem cells[J]. Sci Total Environ, 2019, 651(Pt 1):1038-1046. doi: 10.1016/j.scitotenv.2018.09.247.
[11]	He B, Chen J, Tian M, et al. Adverse effects of nicotine on cardiogenic differentiation from human embryonic stem cells detected by single-cell RNA sequencing[J]. Biochem Biophys Res Commun, 2020, 526(3):848-855. doi: 10.1016/j.bbrc.2020.03.149.
[12]	Collins JM, Keane JM, Deady C, et al. Prenatal stress impacts foetal neurodevelopment: Temporal windows of gestational vulnerability[J]. Neurosci Biobehav Rev, 2024, 164:105793. doi: 10.1016/j.neubiorev.2024.105793.
[13]	Zhang S, Zhao M, Li S, et al. Developmental toxicity assessment of neonicotinoids and organophosphate esters with a human embryonic stem cell- and metabolism-based fast-screening model[J]. J Environ Sci(China), 2024, 137:370-381. doi: 10.1016/j.jes.2023.02.022.
[14]	Feutz AC, De Geyter C. Accuracy, discriminative properties and reliability of a human ESC-based in vitro toxicity assay to distinguish teratogens responsible for neural tube defects[J]. Arch Toxicol, 2019, 93(8):2375-2384. doi: 10.1007/s00204-019-02512-8.
[15]	Shan W, Hu W, Wen Y, et al. Evaluation of atrazine neurodevelopment toxicity in vitro-application of hESC-based neural differentiation model[J]. Reprod Toxicol, 2021, 103:149-158. doi: 10.1016/j.reprotox.2021.06.009. pmid: 34146662
[16]	Liang X, Yin N, Liang S, et al. Bisphenol A and several derivatives exert neural toxicity in human neuron-like cells by decreasing neurite length[J]. Food Chem Toxicol, 2020, 135:111015. doi: 10.1016/j.fct.2019.111015. pmid: 31812737
[17]	Sottile V, Thomson A, McWhir J. In vitro osteogenic differentiation of human ES cells[J]. Cloning Stem Cells, 2003, 5(2):149-155. doi: 10.1089/153623003322234759. pmid: 12930627
[18]	Kääntä E, Parviainen R, Tikanmäki M, et al. Maternal Smoking During Pregnancy and Offspring′s Risk for Bone Fracture in Childhood and Adolescence[J]. J Bone Miner Res, 2023, 38(12):1791-1799. doi: 10.1002/jbmr.4923. pmid: 37823763
[19]	Martinez I, Sparks N, Madrid JV, et al. Exposure to Cigarette Smoke Impedes Human Osteoblast Differentiation Independently of Nicotine[J]. Nicotine Tob Res, 2022, 24(12):1921-1926. doi: 10.1093/ntr/ntac144. pmid: 35778911
[20]	Madrid JV, Vera-Colón M, Zur Nieden NI. Perturbations in Osteogenic Cell Fate Following Exposure to Constituents Present in Tobacco: A Combinatorial Study[J]. Toxics, 2023, 11(12):998. doi: 10.3390/toxics11120998.
[21]	Cheng Z, Liang X, Liang S, et al. A human embryonic stem cell-based in vitro model revealed that ultrafine carbon particles may cause skin inflammation and psoriasis[J]. J Environ Sci(China), 2020, 87:194-204. doi: 10.1016/j.jes.2019.06.016.
[22]	Li B, Jin X, Chan HM. Effects of low doses of methylmercury (MeHg) exposure on definitive endoderm cell differentiation in human embryonic stem cells[J]. Arch Toxicol, 2023, 97(10):2625-2641. doi: 10.1007/s00204-023-03580-7. pmid: 37612375
[23]	Huang X, Huang Z, Gao W, et al. Current Advances in 3D Dynamic Cell Culture Systems[J]. Gels, 2022, 8(12):829. doi: 10.3390/gels8120829.
[24]	Marikawa Y, Chen HR, Menor M, et al. Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells[J]. Reprod Toxicol, 2020, 91:74-91. doi: 10.1016/j.reprotox.2019.10.004. pmid: 31711903
[25]	Noh JS, Jeong JK, Han JW, et al. Rg3 and Rh2 ginsenosides suppress embryoid body formation by inhibiting the epithelial-mesenchymal transition[J]. Arch Pharm Res, 2022, 45(7):494-505. doi: 10.1007/s12272-022-01395-1. pmid: 35759089
[26]	Kirkwood-Johnson L, Marikawa Y. Developmental toxicity of remdesivir, an anti-COVID-19 drug, is implicated by in vitro assays using morphogenetic embryoid bodies of mouse and human pluripotent stem cells[J]. Birth Defects Res, 2023, 115(2):224-239. doi: 10.1002/bdr2.2111.
[27]	Wang Y, Yin N, Yang R, et al. Development of a simplified human embryonic stem cell-based retinal pre-organoid model for toxicity evaluations of common pollutants[J]. Cutan Ocul Toxicol, 2023, 42(4):264-272. doi: 10.1080/15569527.2023.2249988.
[28]	Bu Q, Huang Y, Li M, et al. Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids[J]. Food Chem Toxicol, 2020, 144:111643. doi: 10.1016/j.fct.2020.111643. pmid: 32763439