75: The molecular basis for sonographic cervical shortening: identification of differentially expressed genes as a function of cervical length

Article Outline

• Objective
• Study Design
• Results
• Conclusion
• Copyright

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Objective 

A sonographic short cervix is the most powerful predictor of spontaneous preterm birth, yet the etiology of a short cervix is unknown in most cases. Progestins appear to reduce the rate of preterm birth in women with a sonographic short cervix (<15mm). However, neither the etiology nor the mechanisms responsible for cervical shortening are understood. The purpose of this study was to use transcriptomics to identify changes in gene expression as a function of cervical shortening.

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Study Design 

Women at term not in labor scheduled to have an elective cesarean section were asked to participate in a study in which ultrasound examination was performed before delivery and patients consented to have a cervical biopsy while under anesthesia for the cesarean delivery (n=8). RNA was extracted and the transcriptome profiled with Affymetrix HG-U133PLUS 2.0 arrays. The mRNA expression was analyzed as a function of cervical length using log-linear models. A False Discovery Rate of 5% was used for microarray analysis. qRT-PCR confirmation was performed on selected differentially regulated genes.

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Results 

1) 14 genes were significantly associated with cervical length; 2) The expression of endometrial progesterone-induced protein (EPIP) decreased with cervical length at a rate of 1.51 fold per cm or equivalently 3.9 fold for the entire cervical length range (16-49 mm), p=0.02; 3) qRT-PCR analysis confirmed these findings; 4) These findings remained significant after adjustment for confounders including maternal age (p=0.006).

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Conclusion 

1) We demonstrate that sonographic cervical shortening prior to the onset of labor is associated with specific changes in the transcriptome of the uterine cervix (14 genes) and 2) We have identified and confirmed that cervical shortening is associated with changes in the expression of the endometrial progesterone-induced protein. This protein is up-regulated by progesterone in experimental models and is involved in serine metabolism, which participates in phospholipid synthesis.