Fetal sepsis in utero induces disruption of gene networks involved in cardiac morphogenesis in a nonhuman primate model of infection-induced preterm labor

Fetal lung and brain injury have been linked with intrauterine exposure to amniotic fluid (AF) cytokines, but injury to other fetal organs are not well characterized. Fetal cardiac injury was suspected based on an ultrasound study suggesting diastolic dysfunction, but not previously confirmed or characterized. In this study we explore the relationship between cytokine exposure due to exposure to group B streptococcus and cardiac gene expression. Fetal cardiac tissue was obtained after Cesarean section and fetal necropsy in cases known to have fetal sepsis (N=5) or from saline controls (N=5) in a nonhuman primate model of preterm labor (Macaca nemestrina). Fetal sepsis was induced by choriodecidual inoculation of Group B Streptococcus (N=4) or intra-amniotic inoculation of E. coli (N=1). RNA was extracted from fetal hearts and profiled by microarray. Statistical analysis included Wilcoxon rank sum, single gene analysis, gene set analysis. Results were validated by quantitative RT-PCR.