Abstract

BackgroundCompromised receptivity of the endometrium is a major cause of unexplained infertility, implantation failure and subclinical pregnancy loss. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from early-secretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility.Methods2-D gel electrophoresis was performed to analyze the proteomic changes between early- (n = 8) and mid-secretory (n = 8) phase endometrium of women with unexplained infertility. The differentially expressed protein spots were identified by LC-MS analysis and validated by immunoblotting and immuno-histochemical analysis in early- (n = 4) and mid-secretory (n = 4) phase endometrium of infertile women. Validated proteins were also analyzed in early- (n = 4) and mid-secretory (n = 4) phase endometrium of fertile women.ResultsNine proteins were found to be differentially expressed between early- and mid- secretory phases of endometrium of infertile women. The expression of Ras-related protein Rap-1b, Protein disulfide isomerase A3, Apolipoprotein-A1 (Apo-A1), Cofilin-1 and RAN GTP-binding nuclear protein (Ran) were found to be significantly increased, whereas, Tubulin polymerization promoting protein family member 3, Superoxide dismutase [Cu-Zn], Sorcin, and Proteasome subunit alpha type-5 were significantly decreased in mid- secretory phase endometrium of infertile women as compared to early-secretory phase endometrium of infertile women. Validation of 4 proteins viz. Sorcin, Cofilin-1, Apo-A1 and Ran were performed in separate endometrial biopsy samples from infertile women. The up-regulated expression of Sorcin and down-regulated expression of Cofilin-1 and Apolipoprotein-A1, were observed in mid-secretory phase as compared to early-secretory phase in case of fertile women.ConclusionsDe-regulation of the expression of Sorcin, Cofilin-1, Apo-A1 and Ran, during early- to mid-secretory phase may have physiological significance and it may be one of the causes for altered differentiation and/or maturation of endometrium, in women with unexplained infertility.

Highlights

  • Human endometrium undergoes a series of morphological and molecular changes during the transition from proliferative to secretory phase, under the influence of ovarian steroids [1,2]

  • Several genomics and proteomics approach based studies have revealed large number of differentially regulated genes/proteins by comparing pre-receptive (LH+2) and receptive phase (LH+7) endometrium of fertile women [10,11,12,13]. These studies have provided a large number of molecular candidates that are important during endometrial receptivity and some of them have been established as receptivity markers for fertile endometrium but to date the causes of unexplained infertility are not well explored

  • Comparison of proteomic profile of early-secretory (LH+2) and mid-secretory phase (LH+7) endometrium of women with unexplained infertility were performed by 2D-PAGE analysis

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Summary

Introduction

Human endometrium undergoes a series of morphological and molecular changes during the transition from proliferative to secretory phase, under the influence of ovarian steroids [1,2]. Several genomics and proteomics approach based studies have revealed large number of differentially regulated genes/proteins by comparing pre-receptive (LH+2) and receptive phase (LH+7) endometrium of fertile women [10,11,12,13]. These studies have provided a large number of molecular candidates that are important during endometrial receptivity and some of them have been established as receptivity markers for fertile endometrium but to date the causes of unexplained infertility are not well explored. In order to investigate the changes in endometrial protein profile as a cause of unexplained infertility, the current study was undertaken to analyze the differentially expressed proteins of endometrium from earlysecretory (LH+2) to mid-secretory phase (LH+7), in women with unexplained infertility

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