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


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.
Michigan State University-Spectrum Health Medical Group, Grand Rapids, MI,  USA.
Richard E
RE
Leach
Philip
P
Jessmon
Christos
C
Coutifaris
Michael
M
Kruger
Evan R
ER
Myers
Rouba
R
Ali-Fehmi
Sandra A
SA
Carson
Richard S
RS
Legro
William D
WD
Schlaff
Bruce R
BR
Carr
Michael P
MP
Steinkampf
Susan
S
Silva
Phyllis C
PC
Leppert
Linda
L
Giudice
Michael P
MP
Diamond
D Randall
DR
Armant
D002116:Calcitonin / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005191:Family Characteristics; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008297:Male; D011257:Pregnancy Proteins / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D000071816:Glycodelin; D006023:Glycoproteins; C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D053605:Leukemia Inhibitory Factor; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D002116:Calcitonin