Dynamic genome-wide gene expression and immune cell composition in the developing human placenta.

Area of Science:

• Reproductive Biology
• Genomics
• Immunology

Background:

• The placenta's role in pregnancy is crucial, yet its transcriptomic and immune cell dynamics throughout gestation remain underexplored.
• Understanding these changes is vital for addressing pregnancy-related disorders.

Purpose of the Study:

• To create a comprehensive gene expression map of the human placenta across the first (T1), second (T2), and third (T3) trimesters.
• To analyze transcriptomic differences between maternal and fetal placental tissues at full term.
• To identify temporal and spatial variations in placental gene expression and immune cell composition.

Main Methods:

• RNA-sequencing (RNA-Seq) analysis was performed on 64 biopsy samples from 18 human placentas across T1, T2, and T3.
• Differential gene expression analysis was conducted using DESeq2.
• Immune cell populations were quantified and compared across trimesters.

Main Results:

• 1120 differentially expressed genes were identified between T1 and T3 placentas, with 411 and 709 genes associated with T1 and T3, respectively.
• T1 placenta gene expression was enriched for cell division and proliferation, while T3 showed enrichment for vasculature development and regulation.
• Immune cell populations shifted, with increased monocytes and NK cells in T3 and expanded Hofbauer cells in T2, decreasing in T3. No significant spatial differences were found in T3 placentas.

Conclusions:

• Human placenta gene expression patterns change significantly over gestation but not between maternal and fetal sides.
• The identified gene sets provide a valuable resource for investigating the molecular underpinnings of pregnancy pathologies.
• This study establishes a temporal gene expression atlas for the human placenta.