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Genes Upregulated in Human Fetal Membranes by Infection or Labor

From the Pacific Biomedical Research Center, University of Hawaii, and the Kapiolani Medical Center for Women and Children, Honolulu, Hawaii.

Address reprint requests to: Gillian D. Bryant-Greenwood, PhD Department of Anatomy and Reproductive Biology University of Hawaii 1960 East-West Road Honolulu, HI 96822 E-mail: gbg{at}pbrc.hawaii.edu

Objective: To determine whether suppression subtractive hybridization can detect genes in fetal membranes that are upregulated by infection, preterm premature rupture of membranes (PROM), or labor.

Methods: Using suppression subtractive hybridization, messenger RNAs from a preterm fetal membrane obtained at cesarean delivery without labor (control) were subtracted from a pool of messenger RNAs of three patients with preterm PROM and vaginal delivery. Eight candidate genes identified as upregulated were quantitated by Northern analysis in each of the tissues and in additional patient subgroups.

Results: Eight differentially upregulated genes were identified in preterm labor with PROM. Four of the genes are known to be involved in the response to inflammation or infection, and subsequent histologic examination showed one of the preterm PROM tissues to be infected. F-actin capping protein and chitinase precursor, not previously known to be involved in infection, were also upregulated in the infected tissue from preterm PROM. Northern blots using additional subgroups of patients showed that a regulatory G-protein signaling protein gene was significantly upregulated at term by labor in addition to significant upregulation of interleukin-8. There was a strong correlation between the gene expression for complement factor-B and duration of membrane rupture in the patients with preterm PROM.

Conclusion: Two novel genes potentially involved in the response to inflammation or infection have been identified. A regulatory G-protein signaling protein and interleukin-8 gene expression were upregulated by labor. Complement factor-B gene expression was directly related to the duration of membrane rupture.

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