Seasonally Variant Gene Expression in Full-Term Human Placenta

Abstract

ABSTRACTSeasonal exposures influence human health and development. The placenta, as a mediator of the maternal and fetal systems and a regulator of development, is an ideal tissue to understand the biological pathways underlying relationships between season of birth and later life health outcomes. Here, we conducted a transcriptome-wide association study of season of birth in full-term human placental tissue to evaluate whether the placenta may be influenced by seasonal cues. Of the analyzed transcripts, 583 displayed differential expression between summer and winter births (FDR q<0.05); among these, BHLHE40, MIR210HG, and HILPDA had increased expression among winter births (Bonferroni p<0.05). Enrichment analyses of the seasonally variant genes between summer and winter births indicated over-representation of transcription factors HIF1A, VDR, and CLOCK, among others, and of GO term pathways related to ribosomal activity and infection. Additionally, a cosinor analysis found rhythmic expression for approximately 11.9% of all 17,664 analyzed placental transcripts. These results suggest that the placenta responds to seasonal cues and add to the growing body of evidence that the placenta acts as a peripheral clock, which may provide a molecular explanation for the extensive associations between season of birth and health outcomes.