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

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 Peter Diamond, D. Randall Armant

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 objective of this study was to delineate the developmental dynamics of potentially important proteins in the secretory phase of the menstrual cycle, utilizing a collection of endometrial biopsies from women of fertile (n 89) and infertile (n 89) couples.Methods AND RESULTSProgesterone 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.

Original languageEnglish (US)
Pages (from-to)814-828
Number of pages15
JournalHuman Reproduction
Volume27
Issue number3
DOIs
StatePublished - Jan 1 2012

Fingerprint

Biopsy
Infertility
Proteins
Gene Expression Profiling
Biomarkers
Leukemia Inhibitory Factor
Homeobox Genes
Luteal Phase
antineoplaston A10
Calcitonin
Endometrium
Chemokines
Proteomics
Steroids
Ligands
Pharmaceutical Preparations
Glycodelin

Keywords

  • developmental regulation
  • endometrium
  • idiopathic infertility
  • immunohistochemistry
  • protein expression

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Leach, R. E., Jessmon, P., Coutifaris, C., Kruger, M., Myers, E. R., Ali-Fehmi, R., ... Armant, D. R. (2012). High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples. Human Reproduction, 27(3), 814-828. https://doi.org/10.1093/humrep/der436

High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples. / Leach, Richard E.; Jessmon, Philip; Coutifaris, Christos; Kruger, Michael; Myers, Evan R.; Ali-Fehmi, Rouba; Carson, Sandra A.; Legro, Richard S.; Schlaff, William D.; Carr, Bruce R.; Steinkampf, Michael P.; Silva, Susan; Leppert, Phyllis C.; Giudice, Linda; Diamond, Michael Peter; Armant, D. Randall.

In: Human Reproduction, Vol. 27, No. 3, 01.01.2012, p. 814-828.

Research output: Contribution to journalArticle

Leach, RE, Jessmon, P, Coutifaris, C, Kruger, M, Myers, ER, Ali-Fehmi, R, Carson, SA, Legro, RS, Schlaff, WD, Carr, BR, Steinkampf, MP, Silva, S, Leppert, PC, Giudice, L, Diamond, MP & Armant, DR 2012, 'High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples', Human Reproduction, vol. 27, no. 3, pp. 814-828. https://doi.org/10.1093/humrep/der436
Leach, Richard E. ; Jessmon, Philip ; Coutifaris, Christos ; Kruger, Michael ; Myers, Evan R. ; Ali-Fehmi, Rouba ; Carson, Sandra A. ; Legro, Richard S. ; Schlaff, William D. ; Carr, Bruce R. ; Steinkampf, Michael P. ; Silva, Susan ; Leppert, Phyllis C. ; Giudice, Linda ; Diamond, Michael Peter ; Armant, D. Randall. / High throughput, cell type-specific analysis of key proteins in human endometrial biopsies of women from fertile and infertile couples. In: Human Reproduction. 2012 ; Vol. 27, No. 3. pp. 814-828.
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abstract = "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 objective of this study was to delineate the developmental dynamics of potentially important proteins in the secretory phase of the menstrual cycle, utilizing a collection of endometrial biopsies from women of fertile (n 89) and infertile (n 89) couples.Methods AND RESULTSProgesterone 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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AU - Myers, Evan R.

AU - Ali-Fehmi, Rouba

AU - Carson, Sandra A.

AU - Legro, Richard S.

AU - Schlaff, William D.

AU - Carr, Bruce R.

AU - Steinkampf, Michael P.

AU - Silva, Susan

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AU - Giudice, Linda

AU - Diamond, Michael Peter

AU - Armant, D. Randall

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N2 - 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 objective of this study was to delineate the developmental dynamics of potentially important proteins in the secretory phase of the menstrual cycle, utilizing a collection of endometrial biopsies from women of fertile (n 89) and infertile (n 89) couples.Methods AND RESULTSProgesterone 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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