# Integrated Metabolomic and Transcriptomic Analysis Revealed the Mechanism of BHPF Exposure in Endometrium

**Authors:** Xin Tan, Nengyong Ouyang, Wenjun Wang, Junting Qiu

PMC · DOI: 10.3390/toxics13020100 · Toxics · 2025-01-27

## TL;DR

This study explores how exposure to BHPF affects endometrial cells and reveals concentration-dependent health risks through combined metabolomic and transcriptomic analysis.

## Contribution

The study introduces an integrated metabolomic and transcriptomic approach to uncover BHPF's molecular mechanisms in endometrial cells.

## Key findings

- Low-concentration BHPF exposure affects endometrial cells via primary immunodeficiency pathways involving IL7R and PTPRC.
- High-concentration BHPF exposure reduces cell viability by disrupting purine metabolism and altering genes like PGM1 and PDE3B.
- Integrated analysis reveals concentration-dependent health risks and candidate target genes for further study.

## Abstract

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC. High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1, PDE3B, AK9, and ENTPD8. Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration.

## Linked entities

- **Genes:** IL7R (interleukin 7 receptor) [NCBI Gene 3575], PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788], PGM1 (phosphoglucomutase 1) [NCBI Gene 5236], PDE3B (phosphodiesterase 3B) [NCBI Gene 5140], AK9 (adenylate kinase 9) [NCBI Gene 221264], ENTPD8 (ectonucleoside triphosphate diphosphohydrolase 8) [NCBI Gene 377841]
- **Chemicals:** BHPF (PubChem CID 76716)

## Full-text entities

- **Genes:** PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, PGM1 (phosphoglucomutase 1) [NCBI Gene 5236] {aka CDG1T, GSD14}, PDE3B (phosphodiesterase 3B) [NCBI Gene 5140] {aka HcGIP1, cGIPDE1}, ENTPD8 (ectonucleoside triphosphate diphosphohydrolase 8) [NCBI Gene 377841] {aka E-NTPDase, GLSR2492, NTPDase-8, UNQ2492}, AK9 (adenylate kinase 9) [NCBI Gene 221264] {aka AK 9, AKD1, AKD2, C6orf199, C6orf224, SPGF89}, IL7R (interleukin 7 receptor) [NCBI Gene 3575] {aka CD127, CDW127, IL-7R-alpha, IL-7Ralpha, IL7RA, IL7Ralpha}
- **Diseases:** primary immunodeficiency (MESH:D000081207)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11861605/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC11861605/full.md

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Source: https://tomesphere.com/paper/PMC11861605