2-Ethylhexyl Diphenyl Phosphate Affects Steroidogenesis and Lipidome Profile in Human Adrenal (H295R) Cells
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00141528" target="_blank" >RIV/00216224:14310/25:00141528 - isvavai.cz</a>
Result on the web
<a href="https://pubs.acs.org/doi/10.1021/acs.chemrestox.5c00030" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.chemrestox.5c00030</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/acs.chemrestox.5c00030" target="_blank" >10.1021/acs.chemrestox.5c00030</a>
Alternative languages
Result language
angličtina
Original language name
2-Ethylhexyl Diphenyl Phosphate Affects Steroidogenesis and Lipidome Profile in Human Adrenal (H295R) Cells
Original language description
The ever-increasing use of chemicals and the rising incidence of adverse reproductive effects in the modern environment have become an emerging concern. Several studies have shown that environmental contaminants, such as organophosphate flame retardants (OPFRs), negatively impact reproductive health. To evaluate the potential endocrine-related adverse reproductive effects of widely used and priority-listed compound 2-Ethylhexyl diphenyl phosphate (EHDPP), we characterized its effects on adrenal steroidogenesis in human adrenocortical (H295R) cells. The cells were exposed to EHDPP (1 and 5 mu M) for 48 h, and the production of hormones, including progesterone, androstenedione, testosterone, estradiol, cortisol, and aldosterone, was measured. In addition, LC-MS/MS-based lipidomics analysis was done to quantify intracellular lipid profiles, and transcriptional assays were performed to examine the expression of genes related to corticosteroidogenesis, lipid metabolism, and mitochondrial dynamics. Our findings indicate that EHDPP disrupts hormone regulation in vitro, as evidenced by increased estradiol, cortisol, and aldosterone secretion. The expression of key corticosteroidogenic genes (CYP11B2, CYP21A1, 3 beta-HSD2, and 17 beta-HSD1) was upregulated significantly upon EHDPP exposure. Intracellular lipidomics revealed EHDPP-mediated disruption, including reduced total cholesterol ester, sphingolipids, and increased phospholipids, triglyceride species, and saturated-monounsaturated lipids subspecies. These alterations were accompanied by decreased ACAT2 and SCD1 gene expression. Moreover, a shift in mitochondrial dynamics was indicated by increased MF1 expression and decreased FIS1 expression. These data suggest that EHDPP disrupts adrenal steroidogenesis and lipid homeostasis, emphasizing its potential endocrine-disrupting effects.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30108 - Toxicology
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
CHEMICAL RESEARCH IN TOXICOLOGY
ISSN
0893-228X
e-ISSN
1520-5010
Volume of the periodical
38
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
733-744
UT code for WoS article
001458664800001
EID of the result in the Scopus database
2-s2.0-105001986461