An evidence in vitro for the influence of bisphenol A on uterine leiomyoma

Shen, Yang; Ren, Mulan; Xu, Feng; Cai, Yefeng; Gao, Yongxing; Xu, Qian

doi:10.1016/j.ejogrb.2014.03.052

Cited by 22 publications

(26 citation statements)

References 19 publications

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“…Our previous research on quantitative detection of EEs in samples collected from uterine fibroid patients suggests that the EE exposure levels are significantly higher in women with UL [4,19]. Furthermore, we reported that EEs can promote proliferation of UL cells via upregulating ERgmRNA and protein expression levels, and the effect is enhanced by increasing EE concentration [5,6]. In this study, we also found similar results that either E 2 or each of the EE treatments can promote proliferation by overexpression of ERα [5,6].…”

Section: Discussionsupporting

confidence: 83%

“…The primary cultured UL cells were successfully established and had the ability of passaging four to five generations, referenced to our previous researches [5,6]. Primary and passaged cultured UL cells grow well with forming parallel or radial spindle zonal beam (Fig.…”

Section: Identification Of Ul Cellsmentioning

confidence: 88%

“…Based on data in our previous research [5,6], the optimal dose of EEs was used in this study. The cells were incubated in 100 μl of medium with estradiol (10 −3 μmol/l, E 2 group), bisphenol A (10 μmol/l, BPA group), nonylphenol (32 μmol/l, NP group), octylphenol (8 μmol/l, OP group), or DMSO only (control group).…”

Section: Observation Of Cell Viabilitymentioning

confidence: 99%

“…According to our previous studies on the relationship between EEs and UL cell in vitro [5,6], we hereby try to evaluate if TGF-β3 would regulate UL cell proliferation, which is activated by three phenolic EEs. The effect curve demonstrated E 2 , BPA, and NP accelerated growth of UL cells when compared with untreated UL cells at each time point (p<0.05), while OP has a significant effect on the UL cell proliferation at the 48-and 72-h time point (p<0.05), but not at the 24-h incubation time (p > 0.05) (Fig.…”

Section: Effect Of Tgf-β3 On Uterine Leiomyoma Cell Proliferation Actmentioning

confidence: 99%

“…Some studies suggested that environmental estrogens (EEs) have an impact on the development of UL, which is also supported by our previous researches focused on the effects of in vitro EEs on the proliferation of UL. This proliferation is possibly associated with the increased expressions of IGF-1, VEGF, and other tumor-promoting growth factors mediated by ERα signaling pathway [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor-β signaling pathway cross-talking with ERα signaling pathway on regulating the growth of uterine leiomyoma activated by phenolic environmental estrogens in vitro

Shen

Lü

et al. 2015

Tumor Biol.

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The aim of this paper is to study the participation of transforming growth factor-β (TGF-β) signaling pathway in mediating the growth of human uterine leiomyoma (UL) activated by phenolic environmental estrogens (EEs), via the interaction between TGF-β and ER signaling pathways. The UL cells were prepared by primary culture and subculture methods. To validate the role of TGF-β3 (5 ng/ml) for the viability of human uterine leiomyoma cells, CCK-8 assay was performed in each of five treatment groups including E2 group (E2 10(9) mol/l), BPA group (bisphenol A 10 μmol/l), NP group (nonylphenol 32 μmol/l), OP group (octylphenol 8 μmol/l), or control group (DMSO only). Subsequently, qRT-PCR was applied to detect mRNA expressions of ERα and c-fos, while western blot assay was used to test the expressions of p-Smad3, SnoN, and c-fos proteins in all settings mentioned above; the expressions were compared among different groups, and also in settings with and without synchronous treatment of ICI 182,780. Primarily cultured UL cells were successfully established. Compared with the control group, there were statistically significant increases in the proliferation rate of the UL cells in all EE groups or treated with TGF-β3 only (p < 0.05). Nevertheless, a slight decrease in proliferation rate of UL was detected in coexistence with TGF-β3 in all EE groups (p > 0.05). Interestingly, mRNA expressions of ERα and c-fos reduced in the setting of coexistence of TGF-β3 and EEs compared to isolated EE treatment (p < 0.05). Compared with the control group, the expression of p-Smad3 and c-fos proteins significantly decreased (p < 0.05) in each of E2, BPA, NP, and OP group, and the expression of SnoN protein also significantly reduced only in BPA and NP groups (p < 0.05), followed by TGF-β3 treatment. When adding ICI 182,780, the expression of p-Smad3 protein significantly increased in OP group (p < 0.05), but slightly increased in E2, BPA, NP, and OP groups (p > 0.05). However, compared with the control group, the expressions of SnoN and c-fos proteins significantly decreased (p < 0.05) after adding ICI182,780. Moreover, there was a significant statistical difference in the expression of p-Smad3, SnoN, and c-fos proteins between pre- and post-treatment of ICI 182,780 in all groups (p < 0.05). The ERα signaling pathway and TGF-β signaling pathway have different roles in the control of UL cell proliferation. The phenolic EEs can be a promoter of UL cell proliferation, which is mediated by ERα signaling pathway and its cross-talking with TGF-β signaling pathway. Both less exposure to EEs and blockade of TGF signaling pathway are necessary strategies to prevent UL.

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