ABSTRACT
The aim of this study was to assess the molecular effect of ulipristal acetate (UPA) on gene expression in myometrium and endometrium of patients with symptomatic fibroids. Tissues isolated from four women treated preoperatively with UPA (5 mg) were compared to those from untreated controls using NanoString platform to assess the expression of 75 candidate genes modulated by UPA and ovarian steroids. Deregulated genes were then validated by real-time PCR. In myometrium, UPA exerted an antagonistic effect similar to that observed in fibroids. In UPA-treated endometrium, six genes were identified as highly and significantly upregulated, including matricellular genes CCN1 (54-fold, P = 0.0018) and CCN2 (11-fold, P = 0.00044), Krüppel-like factor 4 (>3-fold, P = 0.0036), and mast cell markers including tryptases TPSAB1/TPSB2 (31-fold, P = 0.023) and carboxypeptidase A (CPA3, 17-fold, P = 0.05). In endometrium, UPA induced the expression of genes involved in fibrogenesis and mast cell function—some of them being widely involved in hepatic injury, which could explain the marked fibrosis and inflammatory cell infiltration observed in explanted livers from patients under UPA treatment.
Author contributions
TA Almeida: studied conception and design, analysis and interpretation of data, and revising the manuscript critically for intellectual content.
D Báez: secured funding, study conception and design, interpretation of data, and revising the manuscript critically for intellectual content.
A Salas: acquisition of data, analysis and interpretation of data, and manuscript drafting.
P Vázquez: acquisition of data, analysis and interpretation of data, and manuscript drafting.
AR Bello: acquisition of data, analysis and interpretation of data, and revising the manuscript critically for intellectual content.
All authors approved this version of the manuscript and agree to be accountable for all aspects of the work.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from that disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
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