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双酚 A 浓缩物优先积聚在人类子宫肌瘤中,并诱导大鼠子宫平滑肌增殖。

Bisphenol A Concentrates Preferentially in Human Uterine Leiomyoma and Induces Proliferation in Rat Myometrium.

机构信息

Department of Obstetrics and Gynecology, Assiut University, Assiut, Egypt Center of Excellence of Stem Cells and Regenerative Medicine CESCRM, Assiut University, Assiut, Egypt

Department of Forensic Medicine and Toxicology, Assiut University, Assiut, Egypt.

出版信息

Reprod Sci. 2016 Apr;23(4):508-14. doi: 10.1177/1933719115608001. Epub 2015 Oct 6.

Abstract

OBJECTIVES

To measure tissue levels of bisphenol A (BPA) in uterine leiomyoma (ULM), adjacent myometrium (Myo-F), and normal myometrium (Myo-N). Also, we tested the effect of BPA treatment on rat myometrium.

METHODS

Uterine leiomyomas and Myo-F tissues were isolated from hysterectomy specimens done to treat symptomatic ULMs (N = 30). Normal myometrium is isolated from hysterectomies done on ULM-free uteri for other benign indications (N = 25). Bisphenol A was measured in 1 g of tissue using solid-phase extraction and high-performance liquid chromatography, with fluorescence detectors. Experimentally, adult female rats were fed BPA orally at a dose of 50 mg/kg/d for 90 days. Animals were killed, and their myometrial thickness and proliferating cell nuclear antigen (PCNA) immunostaining were evaluated.

RESULTS

Tissue concentration of BPA in each of ULM (12.3 ± 2.8 µg/g) and Myo-F (10.1 ± 0.2 µg/g) was significantly higher than that of Myo-N (0.58 ± 0.2 µg/g). There was no statistically significant difference in BPA level between ULM and Myo-F within submucous or interstitial/subserous fibroid groups. Compared to control rats, BPA-treated animals showed significantly higher myometrial thickness (168.67 ± 5.7 µm and 281.6 ± 20.32 µm, respectively, P = .003) and increased myometrial PCNA immunoscores (1.5 ± 0.37 and 10.38 ± 0.67, respectively, P ≤ .001).

CONCLUSION

Bisphenol A concentrates in human ULM tissue and its adjacent Myo-F compared to Myo-N. No significant difference is detected in BPA content of ULM tissue of different subtypes. Bisphenol A increases thickness and induces cellular proliferation in rat myometrium. Taken together, our results support a role of BPA in ULM development/growth.

摘要

目的

测量子宫平滑肌瘤(ULM)、邻近的子宫肌层(Myo-F)和正常子宫肌层(Myo-N)中的双酚 A(BPA)组织水平。此外,我们还测试了 BPA 处理对大鼠子宫肌层的影响。

方法

从因有症状的 ULM 而行子宫切除术的标本中分离 ULM 组织和 Myo-F 组织(N=30)。从因其他良性指征而行子宫切除术且无 ULM 的子宫中分离正常子宫肌层(N=25)。使用固相萃取和高效液相色谱法,荧光检测器测量 1g 组织中的 BPA。在实验中,成年雌性大鼠经口给予 50mg/kg/d 的 BPA 90 天。处死动物,评估其子宫肌层厚度和增殖细胞核抗原(PCNA)免疫染色。

结果

ULM(12.3±2.8µg/g)和 Myo-F(10.1±0.2µg/g)中的组织 BPA 浓度明显高于 Myo-N(0.58±0.2µg/g)。在黏膜下或间质/浆膜下纤维瘤组中,ULM 和 Myo-F 之间的 BPA 水平无统计学差异。与对照组大鼠相比,BPA 处理的动物的子宫肌层厚度明显更高(分别为 168.67±5.7µm 和 281.6±20.32µm,P=0.003),子宫肌层 PCNA 免疫评分也更高(分别为 1.5±0.37 和 10.38±0.67,P≤0.001)。

结论

BPA 集中在人 ULM 组织及其邻近的 Myo-F 中,而不是 Myo-N 中。不同亚型的 ULM 组织中 BPA 含量无显著差异。BPA 增加大鼠子宫肌层的厚度并诱导细胞增殖。综上所述,我们的研究结果支持 BPA 在 ULM 发展/生长中的作用。

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