Multi-omic integration reveals dynamic changes in human placental metabolism across gestation

Area of Science:

• Human placental biology
• Metabolomics
• Pregnancy research

Background:

• Placental metabolic demands evolve dynamically during pregnancy.
• Previous studies primarily focused on term placentas or cell lines, leaving developmental changes understudied.
• Understanding placental metabolome changes across gestation is critical for monitoring pregnancy health.

Purpose of the Study:

• To investigate placental metabolome and metabolite trajectories across trimesters in normal human pregnancy.
• To identify altered metabolic pathways during gestation using integrated metabolomic and transcriptomic data.
• To provide a comprehensive view of placental metabolic function throughout pregnancy.

Main Methods:

• Targeted aqueous metabolomic profiling of 372 metabolites in placental biopsies across three trimesters.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) for metabolite quantification.
• Pathway analysis and multi-omic integration with transcriptomic data for biological interpretation.

Main Results:

• Placental samples clustered by trimester, revealing 5 distinct metabolite trajectories.
• 77% of detectable metabolites (149/193) showed significant differences across trimesters.
• Key metabolic pathways, including amino acid, lipid, and NAD metabolism, were dynamically regulated across gestation.

Conclusions:

• Placental metabolite abundances and pathway activities change substantially throughout pregnancy.
• Integrated multi-omic data offer insights into dynamic metabolic adaptations during gestation.
• These findings enhance understanding of placental function and can inform future pregnancy research.