The molecular basis for sonographic cervical shortening at term: identification of differentially expressed genes and the epithelial-mesenchymal transition as a function of cervical length.
OBJECTIVE
The purpose of this study was to determine whether cervical shortening of a ripe cervix at term is associated with changes in the cervical transcriptome.


METHODS
Sonographically measured cervical lengths and biopsy specimens were obtained from 19 women at term who were not in labor with a ripe cervix. Affymetrix HG-U133 Plus 2.0 arrays (Affymetrix Inc, Santa Clara, CA) were used. Gene expression was analyzed as a function of cervical length. Gene Ontology, pathway analyses, quantitative real-time reverse transcription-polymerase chain reaction, and immunohistochemistry were performed.


RESULTS
Cervical length shortening was associated with differential expression of 687 genes. Fifty-four biologic processes, 22 molecular functions, and 9 pathways were enriched. Quantitative real-time reverse transcription-polymerase chain reaction analysis confirmed differential expression of 13 genes. Bone morphogenetic protein-7, claudin-1, integrin beta-6, and endometrial progesterone-induced protein messenger RNA, and protein expressions were down-regulated with cervical shortening.


CONCLUSIONS
Sonographic cervical shortening in patients at term who are not in labor with a ripe cervix is associated with changes in the uterine cervix transcriptome. The epithelial-mesenchymal transition may participate in the mechanism of cervical shortening at term.
Hassan
Sonia S
SS
Department of Obstetrics and Gynecology, Wayne State University/Hutzel Women’s Hospital, 3990 John R., Detroit, MI 48201, USA. shassan@med.wayne.edu
Romero
Roberto
R
Tarca
Adi L
AL
Nhan-Chang
Chia-Ling
CL
Mittal
Pooja
P
Vaisbuch
Edi
E
Gonzalez
Juan M
JM
Chaiworapongsa
Tinnakorn
T
Ali-Fehmi
Rouba
R
Dong
Zhong
Z
Than
Nandor Gabor
NG
Kim
Chong Jai
CJ
D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D054791:Cervical Length Measurement; D002584:Cervix Uteri / Q000000981:diagnostic imaging* / Q000378:metabolism*; D062445:Claudin-1; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
D055419:Bone Morphogenetic Protein 7; C568108:CLDN1 protein, human; D062445:Claudin-1; D039641:Integrin beta Chains; D008565:Membrane Proteins; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C072170:integrin beta6; C097069:progesterone-induced uterine protein-1, human