Effect of ulipristal acetate on gene expression profile in endometrial cells in culture and in vivo upon post-ovulatory administration in fertile women

Abstract

Purpose

To analyse the effect of ulipristal acetate (UPA) as emergency contraception (EC) on the gene expression of human endometrial cell line (HEC-1A) and endometrium from fertile women treated with UPA after ovulation.

Materials and methods

HEC-1A cells were treated with UPA, and endometrial tissue from four healthy women was collected in cycles before, during and 2 months after post-ovulation pill intake. Ovulation and luteal phase were monitored, and endometrial biopsies were obtained at day LH + 7 in each cycle. In all cases, we analysed the expression profile of 192 genes associated to endometrial receptivity.

Results

We observed a significant change in total transcriptomic activity of UPA-treated HEC-1A cells compared to controls. In vivo, we also observed a trend to down-regulation of genes in the UPA-treated cycle that was partially restored in the post-treatment cycle. Altogether, our results supported a partially reversible effect of UPA in gene expression associated with uterine receptivity.

Conclusions

When UPA was administered after ovulation, it seems to induce a down-regulation of the main genes involved in conditioning the endometrium for implantation. This effect is partially restored two months after pill intake. The action of UPA on the endometrium for users of EC should be further investigated.

摘要

目的：分析醋酸乌利司他(UPA)用作紧急避孕（EC）对子宫内膜细胞系(HEC-1A)及育龄妇女服用UPA后的排卵后子宫内膜基因表达的影响。

材料和方法：用UPA处理HEC-1A细胞, 收集4例健康妇女在服药前、服药中和服药后2个月的子宫内膜组织。监测排卵和黄体期, 并在每个周期LH＋7天取子宫内膜活检。在所有病例中, 我们分析了192个与子宫内膜容受性相关的基因的表达谱。

结果：我们观察到UPA处理的HEC-1A细胞的总转录活性与对照组相比有显著变化。在体内, 我们还观察到在UPA治疗周期中有下调趋势的基因在治疗后的周期中部分恢复。总之, 我们的结果支持：UPA对子宫容受性相关基因表达的影响部分可逆。

结论：在排卵后服用UPA, 似乎诱导子宫内膜着床的主要基因下调。这种影响在服药两个月后部分恢复。UPA用作EC对子宫内膜的作用有待进一步研究。

Keywords:

• Ulipristal acetate
• emergency contraception
• implantation
• gene expression
• endometrium

Acknowledgements

To Lic. Antonio Ballesteros Ribelles for technical assistance in writing this manuscript and Dr. Regine Sitruk-Ware from The Population Council, New York and to Dr. Delphine Levy from HRA, Paris, France for the kindly donation of UPA.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by SINAE, Spain, a grant of the University of Rosario (BIO 565) to MJM, a grant [2015/20504-9] from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and from the Brazilian National Research Council (CNPq) grant No. 573747/2008-3, and partially supported by the National Agency of Scientific and partially supported by the National Agency of Scientific and Technological Promotion (ANPCyT), Argentina grants PICT 2016-1057 to DJC.