Ulipristal Acetate Modifies miRNA Expression in Both Superficial and Basal Layers of the Human Endometrium.

Kamila Kolanska,Maria Sbeih,Perrine Capmas,Martin Koskas,Emile Daraï,Selim Aractingi,Justine Varinot,Nathalie Chabbert-Buffet,Arsène Mekinian,Geoffroy Canlorbe

doi:10.3390/jcm10194442

Abstract

(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary.

Highlights

Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM)
Our results show that UPA modifies the expression of 59 miRNAs, the majority of which have been described as being involved in processes connected to embryo implantation and cancerogenesis
The changes in miRNA expression observed in the basal layer, from which the functional layer renews every month, are different from the molecular changes observed in the superficial layer

Summary

Introduction

Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM). It binds to the major progesterone receptor (PR) isoforms and exerts a wide spectrum of actions, from antagonistic to agonistic effects, depending on the target tissue [1]. It is widely used for emergency contraception and, in some countries, as repetitive 3-month cures in leiomyoma treatment [2]. UPA, like other SPRMs, has a reversible impact on the morphological aspect of the whole endometrium [5]. Endometrial thickening is observed on ultrasound scan in 10% of UPA treated patients, and a specific histological aspect called PR modulator-associated endometrial changes (PAEC) [6,7] has been observed in up to 59% of endometrial biopsies at treatment week 13 with a subsequent decrease to 8% after treatment discontinuation [8]

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