The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: identification of novel molecular functions involved in this process.
OBJECTIVE
The aim of this study was to identify changes in the cervical transcriptome in the human uterine cervix as a function of ripening before the onset of labor.


METHODS
Human cervical tissue was obtained from women at term not in labor with ripe (n = 11) and unripe (n = 11) cervices and profiled using Affymetrix GeneChip HGU133Plus2.0 arrays. Gene expression was analyzed using a moderated t-test (False Discovery Rate 5%). Gene ontology and pathway analysis were performed. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used for confirmation of selected differentially expressed genes.


RESULTS
(1) Ninety-one genes were differentially expressed between ripe and unripe groups. (2) Cervical ripening was associated with enrichment of specific biological processes (e.g. cell adhesion, regulation of anatomical structure), pathways and 11 molecular functions (e.g. extracelluar matrix (ECM)-structural constituent, protein binding, glycosaminoglycan binding). (3) qRT-PCR confirmed that 9 of 11 tested differentially expressed genes (determined by microarray) were upregulated in a ripe cervix (e.g. MYOCD, VCAN, THBS1, COL5A1). (4) Twenty-three additional genes related to ECM metabolism and adhesion molecules were differentially regulated (by qRT-PCR) in ripe cervices.


CONCLUSIONS
(1) This is the first description of the changes in the human cervical transcriptome with ripening before the onset of labor. (2) Biological processes, pathways and molecular functions were identified with the use of this unbiased approach. (3) In contrast to cervical dilation after term labor, inflammation-related genes did not emerge as differentially regulated with cervical ripening. (4) Myocardin was identified as a novel gene upregulated in human cervical ripening.
Hassan
Sonia S
SS
Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women's Hospital, Detroit, MI 48201, USA. shassan@med.wayne.edu
Romero
Roberto
R
Tarca
Adi L
AL
Nhan-Chang
Chia-Ling
CL
Vaisbuch
Edi
E
Erez
Offer
O
Mittal
Pooja
P
Kusanovic
Juan Pedro
JP
Mazaki-Tovi
Shali
S
Yeo
Lami
L
Draghici
Sorin
S
Kim
Jung-Sun
JS
Uldbjerg
Niels
N
Kim
Chong Jai
CJ
D000328:Adult; D020070:Cervical Ripening / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002584:Cervix Uteri / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007745:Labor Onset / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D047929:Term Birth / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099251:Myocardin
D009687:Nuclear Proteins; D015534:Trans-Activators; D000099251:Myocardin