Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining <i>In Vitro</i> Assays and <i>In Silico</i> Modeling

Li, Juan; Cao, Huiming; Feng, Hongru; Xue, Qiao; Zhang, Aiqian; Fu, Jie

doi:10.1021/acs.est.0c03468

Cited by 45 publications

(12 citation statements)

References 58 publications

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“…While another study describes that EGR3 functions as an intracellular mediator of estrogen signaling mechanism in breast cancer. Bother studies provide vital evidence on the association of EGR3 with cancer (Li et al, 2020). In the current study, we found that EGR3 was a highly enriched gene and exhibited a similar expression pattern in both datasets i.e., GSE66359 and GSE45216.…”

Section: Discussionsupporting

confidence: 61%

Untitled

2023

Pak. J. Pharm. Sci.,

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Global incidence of cutaneous squamous cell carcinoma is rising. This study investigated the molecular mechanism of CSCC and screened genes that could serve as biomarkers, providing a theoretical framework for pathogenesis and drug development research. We examined differentially expressed genes (DEGs) between normal tissue specimens and CSCC patient tissues using microarray data analysis.. Also, signal pathway and functional enrichment analysis were employed for target genes to rule out the specific genes that display close association with CSCC with the potential to serve as unique CSCC biomarkers. Two datasets GSE66359 and GSE45216 were used in the differential expression analysis. Results revealed the upregulation of potential candidate genes like P13, MMP1, A100A12, and KRT16 while downregulation of rf132, EGR3, PAMR1, LRP4, and KRT2. Verifying these genes demonstrated that KRT16 and EGR3 had obvious differential expression patterns. Further analyses showed that EGR3 was the only gene that exhibited a similar differential pattern in CSCC. Thus, we infer that EGR3 is closely related to the occurrence and development of CSCC, and it has the potential to function as the candidate biomarker gene against CSCC and facilitate subsequent diagnosis and treatment in clinical management.

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Section: Discussionsupporting

confidence: 61%

Untitled

2023

Pak. J. Pharm. Sci.,

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“…Liu et al found that PFOS could increase mRNA expression of PPARγ, CCAAT/enhancer-binding protein-α (C/EBPα), lipoprotein lipase, and leptin [ 37 ]. Furthermore, animal and in vitro studies have shown that certain PFAS, including PFOA and PFOS, have estrogenic activity and directly interact with estrogen receptors (ERs) [ 38 , 39 , 40 , 41 , 42 , 43 ]. ERs play an important part in energy balance, glucose homeostasis, and lipid metabolism [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

“…ERs play an important part in energy balance, glucose homeostasis, and lipid metabolism [ 44 , 45 ]. Research has indicated that PFAS may disturb transcription mediated by ERs and interfere with ER signaling pathways [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Per- and Polyfluoroalkyl Substances (PFAS) Mixture during Pregnancy and Postpartum Weight Retention in the New Hampshire Birth Cohort Study (NHBCS)

Wang

Howe

Gallagher

et al. 2023

Toxics

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Per- and polyfluoroalkyl substances (PFAS), widely used in industrial and consumer products, are suspected metabolic disruptors. We examined the association between a PFAS mixture during pregnancy and postpartum weight retention in 482 participants from the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate, perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate, were quantified in maternal plasma collected at ~28 gestational weeks. Postpartum weight change was calculated as the difference between self-reported weight from a postpartum survey administered in 2020 and pre-pregnancy weight abstracted from medical records. Associations between PFAS and postpartum weight change were examined using Bayesian kernel machine regression and multivariable linear regression, adjusting for demographic, reproductive, dietary, and physical activity factors; gestational week of blood sample collection; and enrollment year. PFOS, PFOA, and PFNA were positively associated with postpartum weight retention, and associations were stronger among participants with a higher pre-pregnancy body mass index. A doubling of PFOS, PFOA, and PFNA concentrations was associated with a 1.76 kg (95%CI: 0.31, 3.22), 1.39 kg (−0.27, 3.04), and 1.04 kg (−0.19, 2.28) greater postpartum weight retention, respectively, among participants who had obesity/overweight prior to pregnancy. Prenatal PFAS exposure may be associated with increased postpartum weight retention.

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“…Alterations in genes related to estrogenic pathways could also be observed [ 29 ]. Additionally, PFHxS has been showed to be able to exert estrogenic effects [ 45 ]. Thus, the increase in blastocyst rate and cell count seen here could potentially be due to an estrogenous effect exerted by PFHxS, while higher concentrations of PFHxS may cause suppressed development.…”

Section: Discussionmentioning

confidence: 99%

Occurrence of late-apoptotic symptoms in porcine preimplantation embryos upon exposure of oocytes to perfluoroalkyl substances (PFASs) under in vitro meiotic maturation

Leclercq

Hallberg

2022

PLoS ONE

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The objectives of this study were to evaluate the effect of perfluoroalkyl substances on early embryonic development and apoptosis in blastocysts using a porcine in vitro model. Porcine oocytes (N = 855) collected from abattoir ovaries were subjected to perfluorooctane sulfonic acid (PFOS) (0.1 μg/ml) and perfluorohexane sulfonic acid (PFHxS) (40 μg/ml) during in vitro maturation (IVM) for 45 h. The gametes were then fertilized and cultured in vitro, and developmental parameters were recorded. After 6 days of culture, resulting blastocysts (N = 146) were stained using a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and imaged as stacks using confocal laser scanning microscopy. Proportion of apoptotic cells as well as total numbers of nuclei in each blastocyst were analyzed using objective image analysis. The experiment was run in 9 replicates, always with a control present. Effects on developmental parameters were analyzed using logistic regression, and effects on apoptosis and total numbers of nuclei were analyzed using linear regression. Higher cell count was associated with lower proportion of apoptotic cells, i.e., larger blastocysts contained less apoptotic cells. Upon PFAS exposure during IVM, PFHxS tended to result in higher blastocyst rates on day 5 post fertilization (p = 0.07) and on day 6 post fertilization (p = 0.05) as well as in higher apoptosis rates in blastocysts (p = 0.06). PFHxS resulted in higher total cell counts in blastocysts (p = 0.002). No effects attributable to the concentration of PFOS used here was seen. These findings add to the evidence that some perfluoroalkyl substances may affect female reproduction. More studies are needed to better understand potential implications for continued development as well as for human health.

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Evaluation of the Estrogenic/Antiestrogenic Activities of Perfluoroalkyl Substances and Their Interactions with the Human Estrogen Receptor by Combining In Vitro Assays and In Silico Modeling

Cited by 45 publications

References 58 publications

Untitled

Untitled

Per- and Polyfluoroalkyl Substances (PFAS) Mixture during Pregnancy and Postpartum Weight Retention in the New Hampshire Birth Cohort Study (NHBCS)

Occurrence of late-apoptotic symptoms in porcine preimplantation embryos upon exposure of oocytes to perfluoroalkyl substances (PFASs) under in vitro meiotic maturation

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