Transactions of the Twenty-Sixth Annual Meeting of the Society for Maternal-Fetal Medicine
The transcriptome of the uterine cervix before and after spontaneous term parturition

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Objective

This study was designed to identify genes differentially expressed in the human uterine cervix after spontaneous term labor.

Study design

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.

Conclusion

(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.

Section snippets

Study design

A cross-sectional study was performed in patients undergoing elective cesarean section with an unripe cervix (TNL) as well as patients after spontaneous vaginal delivery (TL). The criteria for inclusion were: (1) term gestation (≥37 weeks); (2) no prostaglandin or oxytocin administration; (3) absence of histological chorioamnionitis by examination of the placenta; (4) negative Neisseriae gonorrhea and Chlamydia trachomatis cervical cultures; and (5) normal Papanicolaou smear.

Patients underwent

Results

Microarray analysis was performed on cervical biopsy specimens obtained from 7 patients in the TNL group and 9 patients in the TL group. Clinical characteristics of the patients are described in Table I. Discriminant analysis demonstrated 1192 differentially expressed genes in the cervical biopsies of women who underwent spontaneous labor at term versus those not in labor. A list of the top 50 differentially expressed probe sets is presented in Table II. Hierarchical clustering of the

Comment

Principal findings of the study included the following: (1) the cervical transcriptome of patients after labor was dramatically different (1192 unique genes differentially expressed) from that of those not in labor (false discovery rate < 0.05, absolute fold change > 2); (2) a stereotypic gene expression pattern was observed in cervical tissue after spontaneous vaginal delivery; (3) Gene Ontology analysis indicated multiple “Biological Process” categories were enriched, including “response to

Acknowledgments

We thank Dr. Susan Land, Dan Lott, and Sarah McNorton at the Applied Genomics Technology Center of Wayne State University for the performing the qRT-PCR reactions. We thank Dr. Wendell Jones for critical comments on the manuscript.

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Supported by a Women's Reproductive Health Research Scholar (to S.S.H.) whose research is sponsored by a grant from the National Institutes of Health/National Institute of Child Health and Human Development Grant 2K12HD01254-06.

Presented at the 26th Annual Meeting of the Society for Maternal-Fetal Medicine, January 30 through February 4, 2006, Miami, FL.

Reprints not available from the authors. Address correspondence to Sonia S. Hassan, MD, Hutzel Women's Hospital, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, 3990 John R, Mailbox #4, Detroit, MI 48201.

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