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

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.

Keywords: bisphenol A; myometrium; uterine leiomyoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / metabolism*
  • Benzhydryl Compounds / toxicity
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Female
  • Humans
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • Middle Aged
  • Myometrium / drug effects
  • Myometrium / metabolism*
  • Myometrium / pathology
  • Phenols / administration & dosage
  • Phenols / metabolism*
  • Phenols / toxicity
  • Proliferating Cell Nuclear Antigen / metabolism*
  • Rats
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology

Substances

  • Benzhydryl Compounds
  • Phenols
  • Proliferating Cell Nuclear Antigen
  • bisphenol A