Maternal Undernutrition Induces Cell Signalling and Metabolic Dysfunction in Undifferentiated Mouse Embryonic Stem...

Area of Science:

• Developmental Biology
• Epigenetics
• Nutritional Science

Background:

• Peri-conceptional nutrition significantly impacts offspring health and disease susceptibility.
• Maternal low protein diet (LPD) during mouse preimplantation leads to adult cardiovascular, metabolic, and neurological dysfunction.
• Embryonic stem cell (ESC) lines retain characteristics of in-utero environmental programming.

Purpose of the Study:

• To investigate early molecular mechanisms of dietary environmental programming using ESCs.
• To characterize differences between LPD and normal protein diet (NPD) ESC lines.
• To assess the utility of ESCs for studying peri-conceptional programming.

Main Methods:

• Generation and characterization of ESC lines from LPD and NPD mouse blastocysts.
• Transcriptomics, metabolomics, and bioinformatics analyses.
• Molecular and cellular studies of pluripotency, MAPK signaling, and glucose metabolism.

Main Results:

• LPD ESC lines exhibited reduced derivation capacity but similar pluripotency marker expression.
• Impaired Mitogen-activated protein kinase (MAPK) pathway signaling and reduced cell survival in LPD ESCs.
• Altered glucose metabolism with reduced enzyme expression and PFK activity in LPD ESCs.

Conclusions:

• ESC lines derived from nutritionally programmed embryos retain key phenotypic alterations.
• Peri-conceptional LPD affects crucial developmental pathways including MAPK signaling and glucose metabolism.
• ESCs offer a valuable platform for studying environmental programming with reduced animal use.