Exploring the Effects of Increased Bacteria Exposure on Late Gestation Fetal Sheep

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The concept of the fetal microbiome is beginning to gain traction as new evidence of bacterial presence in fetal tissues arise. With evidence of bacteria in fetal tissues mounting, it becomes important to find out how the fetus responds to increasing presence of bacteria. In our previous studies, we reported that small numbers of bacteria (too few to cause fever or behavioral response) inoculated into the maternal sheep during late gestation can be detected in fetal tissues. In the present study, we hypothesize that transfer of these low numbers of bacteria from mother to fetus stimulate a transcriptomic response in the fetal brain, and that the response is related to inoculation dose. In this study, we used tissues from our previous study in which we inoculated Staphylococcus aureus bacteria into maternal sheep during late gestation. We studied three experimental groups: Naïve (n=6), 300 CFUs (colony forming units injected into the maternal bloodstream) (n=7), and 30,000 CFUs delivered to maternal bloodstream, mouth, and vagina (n=7). Inoculation doses were chosen to ensure low enough dose to not cause fever or anorexia in the sheep. Fetal cerebral cortex samples were collected 3–5 days post inoculation. RNA was extracted and gene expression analyzed using RNAseq. Validation of RNAseq differential expression results was performed using qPCR. Gene expression in the three groups were minimally overlapping in Principal Component Analysis. Using conservative criteria (p<0.05 after Bonferroni correction, we identified 53 differentially expressed genes (DEG) comparing Naïve to 300 CFU and 60 DEG comparing Naïve to 30000 CFU. We conclude that bacteria passing from mother to fetus stimulate transcriptomics responses in the fetal brain. We speculate that this altered gene expression might alter the course of fetal development.Support or Funding InformationThis work was supported by HD033053, AI120195, and HL083810