Placental gene expression signatures based on maternal parity

Area of Science:

• Reproductive Biology
• Genomics
• Perinatal Medicine

Background:

• Nulliparity is associated with adverse pregnancy outcomes, including preeclampsia, preterm birth, and lower birth weight, though the underlying mechanisms remain unclear.
• Placental gene expression patterns differ by parity and fetal sex, potentially influencing placental function and pregnancy outcomes.
• Understanding these placental differences is crucial for addressing disparities in maternal and infant health.

Purpose of the Study:

• To identify differences in placental gene expression between nulliparous and multiparous women.
• To investigate the relationship between these gene expression differences and birth weight.
• To explore the influence of fetal sex on parity-related placental gene expression.

Main Methods:

• RNA sequencing of placental samples from the NICHD Fetal Growth Studies.
• Differential gene expression analysis between nulliparous (n=34) and multiparous (n=41) participants, stratified by fetal sex.
• Weighted gene co-expression network analysis to identify parity-associated modules and correlation with birth weight.

Main Results:

• Five differentially expressed genes were identified (DDX5, ANKRD33, SLITRK6, IL1B, MTCO1P40).
• Two gene co-expression modules ('Grey60', 'Tan') were negatively associated with multiparity.
• Specific genes (DDX5, IL1B) and the 'Grey60' module correlated with birth weight, particularly in groups with lower expression. Enriched pathways included immune response and developmental processes.

Conclusions:

• Placental gene expression variations between nulliparous and multiparous women may contribute to differing neonatal outcomes.
• Fetal sex appears to modulate these parity-associated placental gene expression differences.
• These findings highlight the placenta's role in mediating parity-specific pregnancy outcomes.