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Exposure to Phthalates and Alternative Plasticizers Is Associated with Methylation Changes of ESR1 and PGR in Uterine Leiomyoma: The ELENA Study
- Source :
- Applied Sciences, Vol 11, Iss 4234, p 4234 (2021), Applied Sciences, Volume 11, Issue 9
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Uterine leiomyomas are estrogen-dependent benign tumors with unknown etiologies. Phthalates are endocrine-disrupting chemicals and ubiquitous in the environment<br />thus, it has been suggested that they play a role in the development of uterine leiomyoma. We aimed to investigate whether the pathogenesis of uterine leiomyoma is related to methylation changes in promoter regions of estrogen receptor α (ESR1) and progesterone receptor (PGR) genes in response to phthalates and alternative plasticizers exposure. Urinary concentrations of 20 phthalate metabolites and seven metabolites of di-2-ethylhexyl terephthalate (DEHTP) and di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH) were measured by UHPLC-MS/MS in thirty leiomyoma patients, who provided both paired leiomyoma and myometrium tissues. Methylation levels of ESR1 and PGR were analyzed by pyrosequencing assay. A total of 12 phthalate metabolites and 5 alternative metabolites (3 DEHTP and 2 DINCH) were detected &gt<br />70% among study participants. The methylation of ESR1 and PGR were significantly lower in leiomyoma tissues compared to those in myometrium (18.10 ± 4.41 vs. 28.72 ± 4.95<br />2.32 ± 0.81 vs. 3.27 ± 0.56, respectively). ESR1 methylation in leiomyoma was negatively associated with mono-2-carboxylmethyl-hexyl phthalate (2cx-MMHP) and mono-3-carbocyl-propyl phthalate (MCPP) after adjusting for confounding factors. However, 1-mono-2-ethyl-5-oxohexyl-benzene-1,4-dicarboxylate (5OXO-MEHTP), one of the alternatives, showed positive association with ESR1 methylation in leiomyoma. PGR methylation in leiomyoma was significantly associated with mono butyl phthalate (MnBP), but negatively associated with cyclohexane-1,2-dicarboxylate-mono-7-hydroxy-4-methyl-heptyl ester (cx-MINCH). Our results suggest that phthalates exposure may contribute to leiomyoma pathogenesis via ESR1 and PGR methylation changes.
- Subjects :
- Technology
medicine.medical_specialty
QH301-705.5
QC1-999
Estrogen receptor
010501 environmental sciences
complex mixtures
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
alternative plasticizers
Internal medicine
leiomyoma
Progesterone receptor
medicine
General Materials Science
Biology (General)
neoplasms
PGR
QD1-999
Instrumentation
030304 developmental biology
0105 earth and related environmental sciences
Fluid Flow and Transfer Processes
phthalates
0303 health sciences
Uterine leiomyoma
Chemistry
Physics
Process Chemistry and Technology
General Engineering
Phthalate
Myometrium
ESR1
Methylation
equipment and supplies
Engineering (General). Civil engineering (General)
medicine.disease
female genital diseases and pregnancy complications
Computer Science Applications
body regions
Endocrinology
Leiomyoma
bacteria
methylation
TA1-2040
Estrogen receptor alpha
Subjects
Details
- ISSN :
- 20763417
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Applied Sciences
- Accession number :
- edsair.doi.dedup.....6782f345359ff913ec7e8e628d085628