Downregulation of genes related to immune and inflammatory response in IVF implantation failure cases under controlled ovarian stimulation

Am J Reprod Immunol. 2017 Jul;78(1). doi: 10.1111/aji.12679. Epub 2017 Mar 30.

Abstract

Problem: Implantation failure (IF) even after the good-quality embryo transfer (ET) is main obstacle in in vitro fertilization (IVF). We aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF.

Method of study: Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by microarray. Enrichment analysis of microarray data was performed to determine dysregulated pathways. Microarray results were validated by real-time PCR. Localization of genes related to immune response (progestagen-associated endometrial protein (PAEP), leukaemia inhibitory factor (LIF), interleukin-6 signal transducer (IL6ST) was detected by immunohistochemistry.

Results: The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of PAEP, LIF and IL6ST in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes.

Conclusion: Importance of immune and inflammatory response in endometrial receptivity adds on to the current knowledge of gene expression profile in IF under COS. The panel of genes involved in these pathways would be useful in determining further line of treatment for IF during IVF.

Keywords: endometrial receptivity; gene expression microarray; window of implantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytokine Receptor gp130 / genetics
  • Cytokine Receptor gp130 / immunology
  • Cytokine Receptor gp130 / metabolism
  • Down-Regulation
  • Embryo Implantation / genetics*
  • Embryo Implantation / immunology*
  • Endometrium / immunology
  • Endometrium / metabolism
  • Female
  • Fertilization in Vitro*
  • Gene Expression Profiling
  • Glycodelin / genetics
  • Glycodelin / immunology
  • Glycodelin / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Leukemia Inhibitory Factor / genetics
  • Leukemia Inhibitory Factor / immunology
  • Leukemia Inhibitory Factor / metabolism
  • Oocytes / immunology
  • Oocytes / metabolism
  • Ovary / immunology
  • Ovary / metabolism
  • Young Adult

Substances

  • Glycodelin
  • IL6 protein, human
  • IL6ST protein, human
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • PAEP protein, human
  • Cytokine Receptor gp130