Dataset Information

Effects of PFOA, PFBA, PFHxA, PFOS, PFBS, PFHxS on gene expression in monolayer and non-neuroectoderm cells differentiated from H1

ABSTRACT: Per- and polyfluoroalkyl substances (PFAS) are a group of organic chemicals that contain multiple carbon-fluorine bonds, which make them highly stable and widespread in our environment, even in the human body. They have been detected in cord blood and showed correlation with neonatal health abnormalities such as weight loss. Here, we utilized human embryonic stem cell-based model to assess the early developmental toxicity of six PFAS (PFOA, PFHxA, PFBA, PFOS, PFHxS, and PFBS) and their skin developmental toxicity. We employed global monolayer differentiated model to mimic the early embryonic development and performed non-neural ectoderm (NNE) differentiation which can give rise to keratinocytes to imitate early skin development. Transcriptomic analysis revealed that PFOS caused the most differentially expressed genes (DEGs) both in day 16 global monolayer samples and NNE samples to making it the most toxic of the six PFAS. Further validation of gene expression levels showed that the TGF-β signaling pathways were involved in the early global developmental toxicity and in the early skin developmental toxicity of PFOS. Interestingly, our results showed that PFOS inhibited the ciliogenesis of NNE cells, which may interfere with the transduction of TGF-β, Notch, Hedgehog, and Hippo signaling pathways, ultimately inhibiting early embryonic skin development and posing a potential threat to the occurrence of congenital skin diseases. Overall, our study suggests a potential toxicity mechanism by which PFAS inhibit ciliogenesis to interfere with the transduction of important signaling pathways, leading to early global developmental toxicity as well as early embryonic skin developmental toxicity and potential congenital skin diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236956 | GEO | 2024/04/28

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The potential effects of poly- and perfluoroalkyl substances (PFAS) are a recent human and environmental health concern. There is a persistent link between PFAS exposure and cancer, but the mechanisms are poorly understood. Although epidemiological evidence supporting PFAS exposure and cancer in general is conflicting, there is a relatively strong evidence linking PFAS and testicular germ cell tumors (TGCTs). However, there have been no mechanistic studies to date cancerning PFAS and TGCTs. In this report, the effects of the legacy PFAS, perfluorooctanesulfonic acid (PFOS) and the newer "clean energy" PFAS, lithium bis(trifluoromethylsulfonyl)imide (LiTFSi and called HQ-115) on TGCT tumorigenicity, survival, metabolism, and gene regulation were investigated. In vitro, proliferation and survival of both chemo-sensitive and -resistant TGCT cells were minimally affected by a wide concentration range of PFOS and HQ-115. However, both chemicals promoted the growth of TGCT cells in mouse xenografts at doses consistenet with human exposure but had minimal acute toxicity, as assessed by total body, kidney, and testis weight. PFOS, but not HQ-115, increased liver weight. Transcriptiomic alterations of PFOS-exposed normal mouse testes were dominated by cancer-related pathways and gene expression altersations associated with the H3K27me3 polycomb pathway and DNA methylation, epigenetic pathways were previously shown to be critical for the survival of TGCT cells after cisplatin-based chemotherapy. Similar pattersn of PFOS-mediated gene expression occured in PFOS-exposed cells in vitro. Metabolomic studies revealed that PFOS also altered metabolites associiated with steroid biosynthesis and fatty acid metabolism in TGCT cells, consistent with the proposed ability of PFAS to mimic fatty acied based ligands controlling lipid metabolism and the proposed role of PFAS as endocrine disrupters. Our data, this first cell and animal based study on PFAS in TGCTs, support a pro-tumorigenic effect of PFAS on TGCT biology and suggests epigenetic, metabolic, and endocrine disruption as potential mechanisms of action that are consistent with the non-mutagenic nature of the PFAS class.

Dataset Information

Effects of PFOA, PFBA, PFHxA, PFOS, PFBS, PFHxS on gene expression in monolayer and non-neuroectoderm cells differentiated from H1

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets