Paternal obesity decreases infant MSC mitochondrial functional capacity

Area of Science:

• Reproductive Biology
• Metabolic Health
• Mitochondrial Biology

Background:

• Paternal preconception metabolic health significantly influences fetal metabolic programming and offspring health.
• Mechanisms linking paternal health to offspring metabolism are primarily understood through animal models.
• Mesenchymal stem cells (MSCs) reflect offspring phenotype and are crucial for tissue development and maintenance.

Purpose of the Study:

• To investigate the effects of paternal obesity (P-OB) on infant mesenchymal stem cells (MSCs) in humans.
• To assess mitochondrial function, content, and insulin action in infant MSCs based on paternal BMI.
• To explore the association between paternal obesity, infant MSC metabolic function, and infant growth.

Main Methods:

• Infant MSCs were analyzed from fathers with overweight (P-OW) or obesity (P-OB) [BMI ≥ 30 kg/m²].
• Mitochondrial functional capacity (respiration, OXPHOS, electron transport system) and content were measured.
• Insulin action, glucose handling, and lipid metabolism were assessed in infant MSCs, controlling for maternal factors.

Main Results:

• Infant MSCs from the P-OB group exhibited lower intact cell respiration, OXPHOS, and electron transport system capacity compared to P-OW.
• These mitochondrial deficits occurred independently of changes in mitochondrial content.
• Infants in the P-OB group showed a greater weight-to-length ratio, potentially linked to altered MSC metabolic function.

Conclusions:

• Paternal obesity adversely affects infant MSC mitochondrial respiration and energy production capacity.
• Altered mitochondrial function in infant MSCs may contribute to increased infant weight-to-length ratio.
• These findings highlight the critical role of paternal metabolic health in fetal programming and infant development.