The transcriptome of the uterine cervix before and after spontaneous term parturition.
OBJECTIVE
This study was designed to identify genes differentially expressed in the human uterine cervix after spontaneous term labor.


METHODS
The transcriptome of cervical tissue was characterized using Affymetrix HG-U133 plus 2 microarrays. Samples were collected from patients at term not in labor (n = 7) and after spontaneous labor (n = 9). Microarray statistical analysis included robust multiarray average, reduction of invariant probes, and permutation analysis for differential expression. Real-time quantitative reverse transcriptase-polymerase chain reaction assays of selected genes were performed on a new set of samples from term patients without labor (n = 10) and patients after spontaneous labor (n = 9).


RESULTS
(1) The cervical transcriptome of term patients without labor was dramatically different from that of patients who underwent labor; (2) unique genes (n = 1192) were differentially expressed in the cervical tissue from patients after spontaneous labor, compared with that of the term patients without labor (false discovery rate less than 0.05, absolute fold change greater than 2); (3) Gene Ontology analysis indicated that multiple "Biological Process" categories were enriched, including "response to biotic stimulus," "apoptosis," "epidermis development," and "steroid metabolism"; (4) of major interest, genes involved in neutrophil chemotaxis were dramatically up-regulated in specimens from women after spontaneous labor; (5) real-time quantitative reverse transcriptase-polymerase chain reaction confirmed the increased expression of interleukin-8, interleukin-6, and vascular endothelial growth factor in patients after spontaneous labor; and (6) Toll-like receptor-3 and Toll-like receptor-5 showed decreased gene expression in patients after spontaneous labor. This was confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction.


CONCLUSIONS
(1) Cervical dilatation in term labor is associated with a stereotypic gene expression pattern determined by microarray, which is characterized by overexpression of genes involved in neutrophil chemotaxis, apoptosis, extracellular matrix regulation, and steroid metabolism; (2) Toll-like receptor-3 and Toll-like receptor-5 are differentially regulated during spontaneous parturition at term; and (3) this study provides an unbiased and comprehensive description of the changes in the cervical transcriptome before and after spontaneous term labor.
Hassan
Sonia S
SS
Department of Obstetrics and Gynecology, Wayne State University, Detroit, MI, USA. shassan@med.wayne.edu
Romero
Roberto
R
Haddad
Ramsi
R
Hendler
Israel
I
Khalek
Nahla
N
Tromp
Gerard
G
Diamond
Michael P
MP
Sorokin
Yoram
Y
Malone
John
J
D000293:Adolescent; D000328:Adult; D020070:Cervical Ripening / Q000502:physiology; D002584:Cervix Uteri / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007743:Labor, Obstetric / Q000276:immunology / Q000378:metabolism*; D016014:Linear Models; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015850:Interleukin-6; D016209:Interleukin-8; D051196:Toll-Like Receptor 3; D051198:Toll-Like Receptor 5; D042461:Vascular Endothelial Growth Factor A