Does an increased body mass index affect endometrial gene expression patterns in infertile patients? A functional genomics analysis

Fertil Steril. 2017 Mar;107(3):740-748.e2. doi: 10.1016/j.fertnstert.2016.11.009. Epub 2016 Dec 2.

Abstract

Objective: To analyze the transcriptomic profile of endometrial gene alterations during the window of implantation in infertile obese patients.

Design: Multicenter, prospective, case-control study.

Setting: Three academic medical centers for reproductive medicine.

Patient(s): Infertile patients, stratified into body mass index (BMI) categories according to the World Health Organization guidelines, were included in the study.

Intervention(s): Endometrial samples were obtained from women undergoing standardized estrogen and P replacement cycles after 5 days of vaginal P supplementation.

Main outcome measure(s): To identify endometrial gene expression alterations that occur during the window of implantation in infertile obese patients as compared with infertile normal-weight controls using a microarray analysis.

Result(s): XCL1, XCL2, HMHA1, S100A1, KLRC1, COTL1, COL16A1, KRT7, and MFAP5 are significantly dysregulated during the window of implantation in the receptive endometrium of obese patients. COL16A1, COTL1, HMHA1, KRCL1, XCL1, and XCL2 were down-regulated and KRT7, MFAP5, and S100A1 were up-regulated in the endometrium of obese patients. These genes are mainly involved in chemokine, cytokine, and immune system activity and in the structural extracellular matrix and protein-binding molecular functions.

Conclusion(s): Obesity is associated with significant endometrial transcriptomic differences as compared with non-obese subjects. Altered endometrial gene expression in obese patients may contribute to the lower implantation rates and increased miscarriage rates seen in obese infertile patients.

Clinical trial registration number: NCT02205866.

Keywords: Endometrial gene expression; endometrial receptivity; infertility; metabolic syndrome; obesity.

Publication types

  • Multicenter Study

MeSH terms

  • Abortion, Spontaneous / genetics
  • Abortion, Spontaneous / physiopathology
  • Body Mass Index*
  • California
  • Case-Control Studies
  • Embryo Implantation / genetics
  • Endometrium / chemistry*
  • Endometrium / physiopathology
  • Female
  • Fertility / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genomics* / methods
  • Humans
  • Infertility, Female / diagnosis
  • Infertility, Female / genetics*
  • Infertility, Female / physiopathology
  • Obesity / complications
  • Obesity / diagnosis
  • Obesity / genetics*
  • Obesity / physiopathology
  • Phenotype
  • Pregnancy
  • Prospective Studies
  • Risk Factors
  • Spain
  • Texas
  • Transcriptome*

Substances

  • Genetic Markers

Associated data

  • ClinicalTrials.gov/NCT02205866