High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples

对来自生育和不育夫妇的女性的子宫内膜活检中的关键蛋白质进行高通量、细胞类型特异性分析

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作者:Richard E Leach, Philip Jessmon, Christos Coutifaris, Michael Kruger, Evan R Myers, Rouba Ali-Fehmi, Sandra A Carson, Richard S Legro, William D Schlaff, Bruce R Carr, Michael P Steinkampf, Susan Silva, Phyllis C Leppert, Linda Giudice, Michael P Diamond, D Randall Armant; Reproductive Medicine Netw

Background

Although histological dating of endometrial biopsies provides little help for prediction or diagnosis of infertility, analysis of individual endometrial proteins, proteomic profiling and transcriptome analysis have suggested several biomarkers with altered expression arising from intrinsic abnormalities, inadequate stimulation by or in response to gonadal steroids or altered function due to systemic disorders. The

Conclusions

This approach overcomes the limitations of a small sample number. Protein expression and localization provided important insights into the potential roles of these proteins in normal and pathological development of the endometrium that is not attainable from transcriptome analysis, establishing a basis for biomarker, diagnostic and targeted drug development for women with infertility.

Results

Progesterone receptor-B (PGR-B), leukemia inhibitory factor, glycodelin/progestagen-associated endometrial protein (PAEP), homeobox A10, heparin-binding EGF-like growth factor, calcitonin and chemokine ligand 14 (CXCL14) were measured using a high-throughput, quantitative immunohistochemical method. Significant cyclic and tissue-specific regulation was documented for each protein, as well as their dysregulation in women of infertile couples. Infertile patients demonstrated a delay early in the secretory phase in the decline of PGR-B (P < 0.05) and premature mid-secretory increases in PAEP (P < 0.05) and CXCL14 (P < 0.05), suggesting that the implantation interval could be closing early. Correlation analysis identified potential interactions among certain proteins that were disrupted by infertility. Conclusions: This approach overcomes the limitations of a small sample number. Protein expression and localization provided important insights into the potential roles of these proteins in normal and pathological development of the endometrium that is not attainable from transcriptome analysis, establishing a basis for biomarker, diagnostic and targeted drug development for women with infertility.

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