Advertisement

Predictive biomarkers may allow precision therapy of endometriosis

Abstract

Introduction

Endometriosis is a chronic inflammatory gynecological disorder that causes pelvic pain. Due to the heterogeneity of the disease, response to any treatment in an individual is variable. We aimed to develop in vitro testing that could be adapted for use in precision therapy for endometriosis. We piloted a personalized medicine approach by identifying predictive biomarkers while determining the effect of bazedoxifene (BZA) and medroxyprogesterone acetate (MPA) on the gene expression of a progesterone receptor (PR), an estrogen receptor (ER), and an aromatase (CYP19A1) enzyme in cells cultured from biopsies of endometriosis patients. The differential expression of the most common molecular targets in endometriosis therapy correlated with cellular response.

Methods

Primary eutopic endometrial stromal cells were cultured from endometrial biopsies obtained in secretory phase from women between 24 and 42 years old with moderate-to-severe endometriosis (stages III and IV). Exclusion criteria included use of hormonal treatments and intrauterine contraception in the 6 months prior to surgery. Cells were treated either with BZA, MPA, or vehicle control. Total RNA was extracted from the treated and untreated cells. Differential expression of genes that are involved in the pathogenesis of endometriosis was determined by quantitative reverse transcriptase-polymerase chain reaction analysis.

Results

After determining the baseline expression levels of PRA/B, ERα and CYP19A1, response to treatment was monitored using Ki-67 as a marker of cell proliferation. MPA was effective in blocking proliferation in the group expressing high levels of PRA/B. Endometrium expressing high levels of CYP19A1 preferentially responded to BZA, a selective estrogen receptor modulator known to block estrogen action in endometrium.

Conclusions

PR expression may predict progestin resistance in endometriosis while CYP19A1 expression may indicate the need to block estrogen signaling.

Post author correction

Article Type: ORIGINAL RESEARCH ARTICLE

Article Subject: Basic sciences

DOI:10.5301/jeppd.5000311

Authors

Zhen Hou, Ramanaiah Mamillapalli, Hugh S. Taylor

Article History

Disclosures

Financial support: This work was supported by NIH HD052668, Pfizer W5957335 and Jiangsu Province Government Scholarship for Overseas Studies (JS-2015-082).
Conflict of interest: None of the authors has financial interest related to this study to disclose.

This article is available as full text PDF.

  • If you are a Subscriber, please log in now.

  • Article price: Eur 36,00
  • You will be granted access to the article for 72 hours and you will be able to download any format (PDF or ePUB). The article will be available in your login area under "My PayPerView". You will need to register a new account (unless you already own an account with this journal), and you will be guided through our online shop. Online purchases are paid by Credit Card through PayPal.
  • If you are not a Subscriber you may:
  • Subscribe to this journal
  • Unlimited access to all our archives, 24 hour a day, every day of the week.

Authors

Affiliations

  • Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut - USA
  • State Key Laboratory of Reproductive Medicine, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing - PR China

Article usage statistics

The blue line displays unique views in the time frame indicated.
The yellow line displays unique downloads.
Views and downloads are counted only once per session.

No supplementary material is available for this article.