Nicotine-induced Genetic and Epigenetic Modifications in Primary Human Amniotic Fluid Stem Cells

Area of Science:

• Developmental Biology
• Epigenetics
• Stem Cell Biology

Background:

• Maternal smoking is linked to adverse offspring outcomes, but mechanisms remain unclear.
• Limited human tissue availability hinders research on smoking's molecular effects on fetal development.
• Evidence on smoking-induced molecular and gene expression changes in stem cells is scarce.

Purpose of the Study:

• To investigate the impact of maternal smoking on fetal epigenetic alterations.
• To establish a human amniotic fluid stem cell (hAFSC) model for nicotine exposure.
• To examine nicotine's effects on hAFSC gene expression and differentiation potential.

Main Methods:

• Developed a cell culture model using human amniotic fluid stem cells (hAFSCs).
• Exposed hAFSCs to nicotine (NIC) at a concentration mimicking light maternal smoking.
• Analyzed DNA methylation, N6-methyladenosine (m6A) RNA methylation, gene expression, and differentiation markers.

Main Results:

• Nicotine exposure induced significant DNA and m6A RNA methylation alterations in hAFSCs.
• Nicotine altered the expression of pluripotency genes and cell surface markers, enhancing stemness and impairing differentiation.
• Reduced adipogenic marker expression and H19 hypomethylation were observed, potentially suppressing adipo/lipogenesis.
• Differential expression of 16 miRNAs linked to fetal development pathologies was detected.

Conclusions:

• Nicotine exposure causes multi-level effects on hAFSCs, including epigenetic modifications and altered gene expression.
• Impaired cellular differentiation in hAFSCs may contribute to adverse offspring health outcomes.
• These findings provide insights into the molecular mechanisms linking maternal smoking to developmental consequences.