Deficiency in clonogenic endometrial mesenchymal stem cells in obese women with reproductive failure--a pilot study

PLoS One. 2013 Dec 10;8(12):e82582. doi: 10.1371/journal.pone.0082582. eCollection 2013.

Abstract

Objectives: The mechanisms of obesity associated reproductive complications remain poorly understood. Endometrial mesenchymal stem-cells are critical for cyclic renewal and uterine function. Recently, W5C5(+) cells, with high clonogenicity, capable of producing endometrial stroma in vivo, have been described. We sought to investigate the abundance and cloning efficiency of W5C5(+) and W5C5(-) endometrial cells in relation to Body Mass Index, age and reproductive outcome.

Design: W5C5(+) and W5C5(-) cells were purified from mid-luteal endometrial biopsies (n = 54) by magnetic bead separation and subjected to in vitro colony-forming assays.

Results: First trimester pregnancy losses were significantly higher in obese subjects (n = 12) compared to overweight (n = 20) and subjects with normal Body Mass Index (n = 22) (P<0.05, P<0.01, respectively). W5C5(+) cells (%) were significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). W5C5(+) cloning efficiency was significantly lower in obese subjects compared to overweight and subjects with normal Body Mass Index (P<0.05, respectively). W5C5(-) cloning efficiency was significantly lower in obese subjects compared to subjects with normal Body Mass Index (P<0.05). Body Mass Index was significantly negatively correlated with W5C5(+) cloning efficiency and W5C5(-) cloning efficiency (P<0.01, respectively), and positively correlated with first trimester loss (P<0.01). We found no significant results with age (P>0.05).

Conclusions: Our observations suggest that the regenerative capacity and plasticity of the endometrium of obese women is suboptimal, which in turn may account for the increased risk of reproductive complications associated with obesity.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Embryo Loss / metabolism*
  • Embryo Loss / pathology
  • Endometrium / metabolism*
  • Endometrium / pathology
  • Female
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Obesity / metabolism*
  • Obesity / pathology
  • Pilot Projects
  • Pregnancy
  • Pregnancy Trimester, First / metabolism

Grants and funding

This work was supported by the Biomedical Research Unit in Reproductive Health, a joint initiative between the University Hospitals Coventry and Warwickshire NHS Trust and Warwick Medical School. Dr Caroline Gargett also received funding from The Australian National Health and Medical Research Council for a Senior Research Fellowship 1042298 (CEG) and the Victorian Government’s Operational Infrastructure Support Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.