A high-throughput study of gene expression in preterm labor with a subtractive microarray approach

OBJECTIVE: We propose that elucidation of the pathophysiology of preterm labor can be achieved with genome-scale analyses of differential gene expression. STUDY DESIGN: CD-1 mice on day 14.5 of a 19- to 20-clay gestation were assigned to one of 4 treatment groups modeling different clinical conditions (n = 5 per group): group A, infection with labor (intrauterine injection of 10(10) heat-killed Escherichia coli, which causes delivery within an average of 20 hours); group B, infection without labor (intrauterine injection of 10(7) heat-killed E coli, which leads to normal delivery at term); group C, labor without infection (ovariectomy, which causes delivery within an average of 27 hours); and group D, no infection and no labor (intrauterine injection of vehicle). Total pooled myometrial RNA was prepared 3.5 hours after surgery for groups A, B, and D and 5 hours after surgery for group C. The relative expression of 4963 genes was assayed in these pools by using DNA microarrays. Transcripts specifically involved in infection-induced labor were identified by subtracting from the list of differentially regulated genes in group A those with common expression in groups B and C. RESULTS: In group A 68 differentially expressed transcripts (greater than or equal to2-fold upregulation or downregulation) were identified. Among these are 39 characterized genes. Fourteen (45%) are involved in inflammatory responses, 7 (18%) are involved in growth-differentiation-oncogenesis, and 3 (8%) are involved in apoptosis. Subtraction identified 13 gene products most likely to be important for bacterially induced labor, as opposed to labor without infection or bacterial exposure without labor. CONCLUSION: This study demonstrates the potential of the subtractive DNA microarray technique to identify transcripts important specifically for bacterially induced preterm labor.