Oocyte mitochondria link maternal environment to offspring phenotype

Area of Science:

• Reproductive Biology
• Mitochondrial Biology
• Intergenerational Inheritance

Background:

• Oocytes undergo conserved mitochondrial electron transport chain (ETC) remodeling during maturation, regulated by insulin signaling.
• The biological role of this oocyte ETC remodeling and its underlying molecular mechanisms remain largely unknown.
• Previous work linked maternal insulin signaling to offspring's osmotic stress adaptation via metabolic changes.

Purpose of the Study:

• To elucidate the molecular mechanisms by which oocytes mediate intergenerational stress responses.
• To investigate the role of oocyte ETC remodeling in linking maternal environment to offspring metabolic adaptation.

Main Methods:

• Development of a low-input oocyte proteomics workflow.
• Integration of proteomics with a *Caenorhabditis elegans* intergenerational osmotic stress response model.
• Genetic perturbations of ETC Complex III function and AMP-kinase (AAK-2) pathway analysis.

Main Results:

• Maternal environment and insulin signaling jointly regulate oocyte ETC protein abundance, particularly Complex III.
• Enhanced ETC Complex III function in oocytes is necessary and sufficient to link maternal environment to offspring metabolic changes.
• Oocyte Complex III dysfunction impacts offspring metabolism through an AMP-kinase (AAK-2) dependent pathway.

Conclusions:

• Oocyte ETC remodeling, specifically Complex III activity, serves as a critical link between maternal environment and offspring metabolic adaptation.
• Maternal environment influences offspring's stress resilience by modulating oocyte mitochondrial function.
• The AMP-kinase (AAK-2) pathway in offspring mediates metabolic adjustments for ATP preservation and glycerol metabolism under stress.