Screening of Variants in the Transcript Profile of Eutopic Endometrium from Infertile Women with Endometriosis during the Implantation Window.

Rui Alberto Ferriani,Paula Andrea Navarro,Michele Gomes Da Broi,Jessica Rodrigues Plaça,Wilson Araújo Da Silva

doi:10.1055/s-0041-1730287

Abstract

Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease's context. None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial modulation, it could be a candidate gene for powered further studies evaluating mutations in eutopic endometria from endometriosis patients.

Highlights

Endometriosis, a disease characterized by implantation and growth of endometrial tissue outside the uterine cavity,[1,2] has a high prevalence, affecting between 6 and 10% of women in reproductive age.[1]
None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls
Conclusão Apesar de nenhum padrão de mutação ter sido encontrado, ponderamos o pequeno tamanho da amostra e a análise dos dados de sequenciamento de RNA

Summary

Introduction

Endometriosis, a disease characterized by implantation and growth of endometrial tissue outside the uterine cavity,[1,2] has a high prevalence, affecting between 6 and 10% of women in reproductive age.[1]. Evidence have suggested that changes in the endometrial receptivity, due to molecular and functional disorders in the eutopic endometrium, may be related to impaired fertility in women with endometriosis.[5,7,8,9] The success of embryonic implantation depends on an adequate embryonic development, on the arrival of a competent embryo to a receptive endometrium, and on an efficient communication between the embryo and the endometrium.[10,11,12] It is known that the human endometrium becomes receptive only during the implantation window,[10,13,14,15,16] a certain period that results from the synchronized interaction of a variety of molecules (ovarian hormones, growth factors, transcription factors, cytokines, adhesion molecules), with an important role in establishing uterine receptivity.[16,17,18,19,20,21,22] molecular changes in the eutopic endometrium of these patients could impair their endometrial receptivity, contributing to the infertility observed in women with the disease

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