Ceramide and its transport protein (CERT) contribute to deterioration of mitochondrial structure and function in

Loro L Kujjo1, Beth M Acton, Guy A Perkins

  • 1Department of Human Anatomy, Michigan State University, East Lansing, MI 48824, USA.

Insights

Aging oocytes show reduced quality due to ceramide changes impacting mitochondria. Restoring ceramide and mitochondrial function can improve oocyte developmental potential in aging.

Area of Science:

  • Reproductive Biology
  • Cellular Aging
  • Mitochondrial Biology

Background:

  • Oocyte quality and developmental potential decline with advanced maternal age in women and mice.
  • Previous research has not fully elucidated the molecular mechanisms underlying age-related oocyte quality decline.

Purpose of the Study:

  • To investigate the role of ceramide and mitochondrial dysfunction in age-related oocyte quality decline.
  • To identify potential therapeutic targets for ameliorating aging phenotypes in oocytes.

Main Methods:

  • Analysis of ceramide levels, mitochondrial function (ROS, ATP), and structure in young and aged oocytes.
  • Mitochondrial transplantation experiments from young to aged oocytes.
  • Co-treatment of aged oocytes with ceramide and l-carnitine.
  • Investigation of ceramide transport protein (CERT) role using knockdown techniques.

Main Results:

  • Aged oocytes exhibited decreased ceramide levels, reduced ROS and ATP, and altered mitochondrial morphology and function.
  • Mitochondrial transplantation improved aged oocyte developmental potential.
  • Ceramide and l-carnitine co-treatment rescued mitochondrial function and prevented fragmentation in aged oocytes.
  • Downregulation of CERT and specific ceramide level manipulations replicated the aging phenotype.

Conclusions:

  • Age-related oocyte deterioration involves alterations in ceramide levels and mitochondrial function.
  • Changes in ceramide and CERT contribute to mitochondrial structural and functional decline in aging oocytes.
  • Targeting ceramide metabolism and mitochondrial health may offer strategies to improve oocyte quality.

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