A proteomic analysis of the endometrium in obese and overweight women with recurrent miscarriage: preliminary evidence for an endometrial defect.

Mostafa Metwally,Tin Li,Jerry Thomas,Rebecca Preece,William Ledger

doi:10.1186/1477-7827-12-75

Abstract

BackgroundOverweight and obese women have been shown to have an increased risk of recurrent miscarriage as well as other adverse reproductive outcomes, but it is yet unclear whether this is due to an effect on the endometrium, embryo or both. The current study employs proteomic analysis to examine for a potential endometrial defect in obese and overweight women with recurrent miscarriage.MethodsProteomic tissue analysis of 21 endometrial samples obtained In the midluteal phase from 16 women with recurrent miscarriage (obese, n = 12 and lean, n = 4) and 5 fertile volunteers (Obese, n = 2 and Lean, n = 3). Proteins were separated using 2-D gel electrophoresis and principle component analysis was used to quantitatively compare protein expression between groups. Protein spots showing significantly altered expression were identified using mass spectrometry.ResultsObese and overweight recurrent miscarriage patients had a significantly increased endometrial expression of haptoglobin compared to their lean counterparts (p = 0.01). These patients also displayed a significant increase in endometrial expression of transthyretin (p = 0.04) and beta- globulin (p = 0.04). Principle Component Analysis (PCA) of the studied groups also demonstrated that endometrial samples could be grouped based on differences in the BMI, suggesting that obesity is an independent factor influencing endometrial protein expression.ConclusionsThese findings provide preliminary evidence for an alteration in the endometrial protein profile in overweight/obese women with recurrent miscarriage mainly in the form of increased haptoglobin, an inflammatory marker associated with obesity.

Highlights

Overweight and obese women have been shown to have an increased risk of recurrent miscarriage as well as other adverse reproductive outcomes, but it is yet unclear whether this is due to an effect on the endometrium, embryo or both
Study population Endometrial samples from 16 consecutive women suffering from recurrent miscarriage and consenting to participation were included as the study group
Twelve of the 16 endometrial samples from the recurrent miscarriage group were obtained from women with unexplained recurrent miscarriage

Summary

Introduction

Overweight and obese women have been shown to have an increased risk of recurrent miscarriage as well as other adverse reproductive outcomes, but it is yet unclear whether this is due to an effect on the endometrium, embryo or both. There is growing evidence that an increase in body mass index (BMI) is associated an increased risk of miscarriage [1,2,3] It is unknown if this association is due to an adverse effect on the embryo, endometrium or both. To prospectively examine all possible endometrial factors using immunocytochemical staining or other molecular techniques could be a time consuming and possibly unrevealing process, so we postulated that by mapping the endometrial protein profile around the time of implantation, potential target proteins could be identified for further investigation.

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