Ra. Muhle et al., A high-throughput study of gene expression in preterm labor with a subtractive microarray approach, AM J OBST G, 185(3), 2001, pp. 716-724
OBJECTIVE: We propose that elucidation of the pathophysiology of preterm la
bor can be achieved with genome-scale analyses of differential gene express
ion.
STUDY DESIGN: CD-1 mice on day 14.5 of a 19- to 20-clay gestation were assi
gned to one of 4 treatment groups modeling different clinical conditions (n
= 5 per group): group A, infection with labor (intrauterine injection of 1
0(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 aver
age of 27 hours); and group D, no infection and no labor (intrauterine inje
ction 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 m
icroarrays. Transcripts specifically involved in infection-induced labor we
re identified by subtracting from the list of differentially regulated gene
s in group A those with common expression in groups B and C.
RESULTS: In group A 68 differentially expressed transcripts (greater than o
r equal to2-fold upregulation or downregulation) were identified. Among the
se 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 m
ost likely to be important for bacterially induced labor, as opposed to lab
or without infection or bacterial exposure without labor.
CONCLUSION: This study demonstrates the potential of the subtractive DNA mi
croarray technique to identify transcripts important specifically for bacte
rially induced preterm labor.