Abstract #500

# 500
Physiology and pathophysiology of the microbiome and immune-related genes in development of the fetal brain.
C. E. Wood*1, M. B. Rabaglino1, M. A. Zarate1, E. I. Chang1, 1Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL.

Fetuses are commonly understood to develop in a sterile environment, and it is generally understood that bacterial invasion of the intrauterine environment predisposes the pregnancy to preterm birth. We have performed 2 studies that suggest that bacteria may play a role in the development of the fetus and preparation for birth and extrauterine life. To identify the major pattern of gene expression in the developing fetal sheep brain in the latter half of gestation, we used microarray technology to model gene expression in cerebral cortex, hypothalamus, hippocampus, and medullary brainstem at 80, 100, 120, 130, and 145 d gestation prenatally (term = 147 d) and 1 and 7 d postnatally. The differentially expressed genes (DEG) were analyzed using Supervised Weighted Gene Co-expression Network Analysis. The gene ontology analysis revealed that genes expressed by immune cells of the hematopoietic lineage (from the hematopoietic stem cells to more differentiated cells, for example macrophage, dendritic cells and T cells) are being transcribed at an increasing rate toward the last stage of gestation and transition to the extra-uterine life. We proposed that this gene expression pattern might be stimulated by the presence of bacteria in the fetal brain. qPCR experiments revealed an increasing abundance of bacterial 16S rRNA in the fetal brain in the latter half of gestation, approximating the rise in gene expression of the immune system within the brain. In other experiments, we discovered that maternal stress (ventilatory hypoxia) causes migration of bacteria into the fetal circulation and stimulates inflammatory pathways in fetal brain and other tissues. Bacterial populations appearing in fetal brain after maternal stress are relatively non-diverse: Staphylococcus simulans and other Staphylococcus species predominate. Together, our studies suggest that, in normal fetuses, there is a fetal microbiome. We propose that the presence of small numbers of bacteria may help direct fetal immune development and that the migration of bacteria into the fetus can be stimulated in conditions of maternal stress.

Key Words: fetal brain, microbiome

Speaker Bio
Dr. Wood’s laboratory is focused on the mechanisms controlling the fetal responses to stress and the mechanism of prematurity. Our experimental model is the chronically catheterized fetal sheep model, and our work combines a wide range of techniques including in vivo experimentation, molecular biology endpoints, and systems biology analysis of transcriptomics.

Degrees and Training
  • AB in Biochemistry, University of California, Berkeley
  • PhD in Endocrinology, University of California, San Francisco
  • Postdoctoral fellowship in Fetal Physiology, University of California, San Francisco