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

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Low birthweight centile in males is linked to adverse outcomes, potentially due to altered androgen receptor (AR) signaling in the placenta. This study reveals changes in AR-regulated genes may impair placental vasculature and fetal growth.

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androgen receptorandrogen response elementfetal growthplacenta transcriptome

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Area of Science:

  • Reproductive Biology
  • Genomics
  • Perinatal Medicine

Background:

  • Birthweight centile (BWC) below the 25th percentile is linked to adverse perinatal outcomes, especially in males.
  • Male vulnerability may involve placenta-specific androgen signaling via the androgen receptor (AR) and androgen response elements (AREs).

Purpose of the Study:

  • To investigate global and ARE-specific transcriptomic signatures in term male placentae across different BWC subcategories.
  • To explore the relationship between ARE-containing transcripts, placental function, and fetal growth.

Main Methods:

  • RNA sequencing (RNA-seq) was used to analyze transcriptomes of term male placentae (≥37 weeks gestation).
  • Gene set enrichment analysis identified functional pathways associated with BWC subcategories (<10th, 10th-30th, >30th).

Main Results:

  • Placentae with BWCs <10th percentile showed upregulated ARE-containing transcripts, linked to hypoxia and suppressed mitochondrial function.
  • In silico analysis indicated <10th and 10th-30th BWC placentae upregulated vasculature, immune, and cell adhesion gene sets.

Conclusions:

  • Altered expression of ARE-containing transcripts in male placentae may impair placental vasculature.
  • This impairment, suggested by in silico findings, could contribute to reduced fetal growth and adverse perinatal outcomes.