Placenta-Specific Transcripts Containing Androgen Response Elements Are Altered In Silico by Male Growth Outcomes

Ashley S. Meakin, Melanie Smith, Janna L. Morrison, Claire T. Roberts, Martha Lappas, Stacey J. Ellery, Olivia Holland, Anthony Perkins, Sharon A. McCracken, Vicki Flenady, Vicki L. Clifton

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Abstract

A birthweight centile (BWC) below the 25th is associated with an elevated risk of adverse perinatal outcomes, particularly among males. This male vulnerability may stem from alterations in placenta-specific androgen signalling, a signalling axis that involves the androgen receptor (AR)-mediated regulation of target genes containing androgen response elements (AREs). In this study, we examined global and ARE-specific transcriptomic signatures in term male placentae (≥37 weeks of gestation) across BWC subcategories (<10th, 10th–30th, >30th) using RNA-seq and gene set enrichment analysis. ARE-containing transcripts in placentae with BWCs below the 10th percentile were upregulated compared to those in the 10th–30th and >30th percentiles, which coincided with the enrichment of gene sets related to hypoxia and the suppression of gene sets associated with mitochondrial function. In the absence of ARE-containing transcripts in silico, <10th and 10th–30th BWC subcategory placentae upregulated gene sets involved in vasculature development, immune function, and cell adhesion when compared to those in the >30th BWC subcategory. Collectively, our in silico findings suggest that changes in the expression of ARE-containing transcripts in male placentae may contribute to impaired placental vasculature and therefore result in reduced fetal growth outcomes.

Original languageEnglish
Article number1688
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume25
Issue number3
DOIs
Publication statusPublished - 1 Feb 2024

Keywords

  • androgen receptor
  • androgen response element
  • fetal growth
  • placenta transcriptome

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