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

Am J Obstet Gynecol. 2001 Sep;185(3):716-24. doi: 10.1067/mob.2001.117183.

Abstract

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-day 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 (>or=2-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Bacterial Infections / complications
  • Female
  • Gene Expression*
  • Inflammation / complications
  • Mice
  • Mice, Inbred Strains
  • Neoplasms / complications
  • Obstetric Labor, Premature / etiology
  • Obstetric Labor, Premature / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Pregnancy Complications / physiopathology
  • Pregnancy Complications, Infectious / physiopathology
  • Transcription, Genetic