Ku T(1)(2), Hao F(1), Yang X(1), Rao Z(1), Liu QS(1), Sang N(2), Faiola F(1)(3), Zhou Q(1)(3)(4), Jiang G(1)(3)(4). Author information:
(1)State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research
Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing
100085, China.
(2)College of Environment and Resource, Research Center of Environment and
Health, Shanxi University, Taiyuan 030006, China.
(3)College of Resources and Environment, University of Chinese Academy of
Sciences, Beijing 100049, China.
(4)School of Environment, Hangzhou Institute for Advanced Study, University of
Chinese Academy of Sciences, Hangzhou 310000, China.
The tremendous potential for graphene quantum dots (GQDs) in biomedical applications has led to growing concerns of their health risks in human beings. However, present studies mainly focused on oxidative stress, apoptosis, and other general toxicity effects; the knowledge on the developmental toxicity and the related regulatory mechanisms is still far from sufficient. Our study revealed the development retardation of mouse embryonic stem cells (mESCs) caused by GQDs with a novel DNA methylation epigenetic mechanism. Specifically, GQDs were internalized into cells mainly via energy-dependent endocytosis, and a significant fraction of internalized GQDs remained in the cells even after a 48-h clearance period. Albeit with unobservable cytotoxicity or any influences on cell pluripotency, significant retardation was found in the in vitro differentiation of the mESCs into embryoid bodies (EBs) with the upregulation of Sox2 levels in GQD pretreatment groups. Importantly, this effect could be contributed by GQD-induced inhibition in CpG methylation of Sox2 through altering methyltransferase and demethyltransferase transcriptional expressions, and the demethyltransferase inhibitor, bobcat339 hydrochloride, reduced GQD-induced upregulation of Sox2. The current study first demonstrated that GQDs compromised the differentiation program of the mESCs, potentially causing development retardation. Exposure to this nanomaterial during gestation or early developmental period would cause adverse health risks and is worthy of more attention.
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