Seasonal Gene Expression in Human Placenta

Abstract

Background: Seasonal 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. Rhythmic seasonal gene expression in the placenta could provide a molecular explanation for the associations between season of birth and later life disease.Methods: We investigated whether transcriptome-wide placental gene expression had seasonal or monthly patterns in the Rhode Island Child Health Study (RICHS). We performed a differential expression analysis of season of birth, defined by the solstice and equinox dates to bin by photoperiod. Additionally, we evaluated whether placental gene expression displayed rhythmicity by conducting a cosinor analysis of birth month. Results were adjusted for multiple comparisons using the Benjamini and Hochberg or Bonferroni methods.Results: 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 (Bon p<0.05). Enrichment analyses indicated over-representation of transcription factors HIF1A, VDR, and CLOCK, among others, and of GO term pathways related to ribosomal activity and infection between summer and winter births. Additionally, the cosinor analysis found rhythmic expression for approximately 11.9% of all 17,664 analyzed placental transcripts.Conclusion: These results suggest that the placenta responds to seasonal cues and acts as a peripheral clock; results also suggest seasonal changes in placental inflammation and hypoxia, which may provide a molecular explanation for the extensive associations between season of birth and health outcomes. Further study of seasonal and circadian effects on the placenta could shed light on the pathways that influence the associations between season of birth and human health, as well as possible therapeutic targets.