Analysis of the inï¿½vitro effects of di‑(2‑ethylhexyl) phthalate exposure on human uterine leiomyoma cells

Kim, Jin Hee

doi:10.3892/etm.2018.6040

Cited by 14 publications

(15 citation statements)

References 55 publications

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“…However, a highly inflammatory milieu rich in TNF- can compromise the intestinal epithelial barrier, further exacerbating inflammatory and apoptotic conditions. In vitro studies have shown that high-molecular-weight phthalates including DEHP alter the expression of genes involved in cell cycle and apoptotic pathways in human leiomyoma cells 29 , ovarian antral follicles 30 , and spermatocytes 29 , 31 . Disruptions in the cell cycle can either lead to abnormal cell proliferation and/or apoptosis, and this may depend on the cell type.…”

Section: Introductionmentioning

confidence: 99%

Subacute exposure to di-isononyl phthalate alters the morphology, endocrine function, and immune system in the colon of adult female mice

Bashir

Nowak

Mei

et al. 2020

Sci Rep

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Di-isononyl phthalate (DiNP), a common plasticizer used in polyvinyl chloride products, exhibits endocrine-disrupting capabilities. It is also toxic to the brain, reproductive system, liver, and kidney. However, little is known about how DiNP impacts the gastrointestinal tract (GIT). It is crucial to understand how DiNP exposure affects the GIT because humans are primarily exposed to DiNP through the GIT. Thus, this study tested the hypothesis that subacute exposure to DiNP dysregulates cellular, endocrine, and immunological aspects in the colon of adult female mice. To test this hypothesis, adult female mice were dosed with vehicle control or DiNP doses ranging from 0.02 to 200 mg/kg for 10–14 days. After the treatment period, mice were euthanized during diestrus, and colon tissue samples were subjected to morphological, biochemical, and hormone assays. DiNP exposure significantly increased histological damage in the colon compared to control. Exposure to DiNP also significantly decreased sICAM-1 levels, increased Tnf expression, decreased a cell cycle regulator (Ccnb1), and increased apoptotic factors (Aifm1 and Bcl2l10) in the colon compared to control. Colon-extracted lipids revealed that DiNP exposure significantly decreased estradiol levels compared to control. Collectively, these data indicate that subacute exposure to DiNP alters colon morphology and physiology in adult female mice.

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Section: Introductionmentioning

confidence: 99%

Subacute exposure to di-isononyl phthalate alters the morphology, endocrine function, and immune system in the colon of adult female mice

Bashir

Nowak

Mei

et al. 2020

Sci Rep

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“…Moreover, several of the mRNA gene targets identified in our analysis (eg, PTEN, ADORA2B, KIT, E2 F3) are associated with proteins that were over-expressed in phthalate-treated fibroid cells. 49-52 Kim and colleagues 53,54 reported that exposing human fibroid cells to DEHP enhanced cell proliferation, blocked apoptosis, and induced protein expression of HIF-1α, COX-2, PCNA, and BLC2. It is plausible that the toxicity demonstrated in vitro is partly mediated through miRNA regulation.…”

Section: Discussionmentioning

confidence: 99%

Phthalate Exposures and MicroRNA Expression in Uterine Fibroids: The FORGE Study

et al. 2020

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Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (q interaction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.

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“…These results indicate that DEHP has nonmonotonic effects in uterus. Recently, it has been reported that DEHP induced leiomyoma cells to have higher viability and lower apoptosis rate (Kim, 2018). In vitro treatment with DEHP has suggested increased viability of endometrial stromal cells, a precondition to endometriosis (Scsukova et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Chronic Low-Dose Nonylphenol or Di-(2-ethylhexyl) Phthalate has a Different Estrogen-like Response in Mouse Uterus

Kim¹,

Cha²,

Lee³

et al. 2018

Dev. Reprod.

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Through the development of organic synthetic skill, chemicals that mimic signaling mediators such as steroid hormones have been exposed to the environment. Recently, it has become apparent that this circumstance should be further studied in the field of physiology. Estrogenic action of chronic low-dose nonylphenol (NP) and di-(2-ethylhexyl) phthalate (DEHP) in mouse uterus was assessed in this study. Ten to twelve-week-old female mice (CD-1) were fed drinking water containing NP (50 or 500 μg/L) or DEHP (133 or 1,330 μg/L) for 10 weeks. Uterine diameter, the thickness of myometrium and endometrium, and the height of luminal epithelial cells were measured and the number of glands were counted. The expression levels of the known 17β-estradiol (E2)-regulated genes were evaluated with real-time RT-PCR methodology. The ration of uterine weight to body weight increased in 133 μg/L DEHP. Endometrial and myometrial thickness increased in 133 and 1,330 μg/L DEHP treated groups, and in 50, 500 μg/L NP and 133 μg/L DEHP, respectively. The height of luminal epithelial cell decreased in NP groups. The numbers of luminal epithelial gland were decreased in NP groups but increased in 50 μg/L DEHP group. The histological characters of glands were not different between groups. The mRNA expression profiles of the known 17β-estradiol (E2) downstream genes, Esr1, Esr2, Pgr, Lox, and Muc1, were also different between NP and DEHP groups. The expression levels dramatically increased in some genes by the NP or DEHP. Based on these results, it is suggested that the chronic low-dose NP or DEHP works as estrogen-like messengers in uterus with their own specific gene expression-regulation patterns.

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Analysis of the inï¿½vitro effects of di‑(2‑ethylhexyl) phthalate exposure on human uterine leiomyoma cells

Cited by 14 publications

References 55 publications

Subacute exposure to di-isononyl phthalate alters the morphology, endocrine function, and immune system in the colon of adult female mice

Subacute exposure to di-isononyl phthalate alters the morphology, endocrine function, and immune system in the colon of adult female mice

Phthalate Exposures and MicroRNA Expression in Uterine Fibroids: The FORGE Study

Chronic Low-Dose Nonylphenol or Di-(2-ethylhexyl) Phthalate has a Different Estrogen-like Response in Mouse Uterus

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