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Gene Expression Profiling of Cervical Tissue During Physiological Cervical Effacement

Ambros Huber, MD^*, Gernot Hudelist, MD, Klaus Czerwenka, MD, Peter Husslein, MD^*, Ernst Kubista, MD and Christian F. Singer, MD

From the *Division of Obstetrics and Division of Special Gynecology, Department of OB/GYN, Medical University of Vienna; Department of Obstetrics and Gynecology, LKH Villach and Ludwig Boltzmann Institute for Clinical and Experimental Oncology; and Division of Gynecopathology, Department of Pathology, Medical University of Vienna, Vienna, Austria.

Address reprint requests to: Christian F. Singer, MD, Department of OB/GYN, Vienna Medical University, Waehringer Guertel 18–20, A-1090 Vienna, Austria; e-mail: christian.singer{at}meduniwien.ac.at.

OBJECTIVE: The softening and dilation of cervical tissue during parturition requires a rapid reorganization of extracellular matrix and cellular interactions. The purpose of this study was to gain insight into the complex transformational changes in gene expression that lead to cervical effacement.

METHODS: Cervical biopsies from effaced cervices of 10 women undergoing spontaneous vaginal delivery and from competent cervices of 10 women undergoing primary cesarean delivery were collected at 37–41 weeks of gestation and subjected to differential complementary DNA (cDNA) microarray analysis. Gene expression results were validated by real-time polymerase chain reaction (PCR).

RESULTS: In a cDNA array that enables the analysis of the differential gene expression of more than 600 genes, the messenger (m)RNA expression of 40 genes increased more than 2.5-fold during cervical ripening. The majority of these genes encode cytokines, transcription factors, and cell-matrix–associated proteins. The mRNA expression of 6 genes decreased to less than 0.5-fold. The remaining 556 genes were not significantly altered. Real-time PCR analysis performed for selected, highly up-regulated genes confirmed our cDNA array findings.

CONCLUSION: Complete cervical effacement is associated with a characteristic and profound alteration in the gene expression profile of cervical cells. We hypothesize that an understanding of the molecular events that accompany physiological cervical dilation is pivotal to an understanding of pathological conditions such as premature delivery and postterm pregnancy.

LEVEL OF EVIDENCE: II-2

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