MUC1 Protects Preimplantation Embryos In Vitro via Clearance of ROS by Triggering Mitophagy

Area of Science:

• Cell Biology
• Developmental Biology
• Reproductive Science

Background:

• Assisted reproductive technology (ART) exposes embryos to stressors, increasing reactive oxygen species (ROS) that impact development.
• Mitophagy, the clearance of damaged mitochondria, is essential for embryonic development, but its regulation in early embryos is poorly understood.

Purpose of the Study:

• To investigate the role of Mucin 1 (MUC1) in regulating mitophagy during early embryonic development.
• To explore the underlying mechanisms of MUC1-mediated mitophagy and its impact on blastocyst formation.

Main Methods:

• Studied MUC1 expression in mouse and human oocytes and blastocysts.
• Generated Muc1 knockout mouse embryos to assess its function in vitro.
• Analyzed mitochondrial ROS levels and mitophagy markers (PINK1/PARK2).
• Utilized mitophagy stimulators (CCCP) and antioxidants (Vitamin C) to evaluate rescue effects.

Main Results:

• MUC1 expression is present in oocytes and peaks at the blastocyst stage.
• Muc1 knockout impairs blastocyst formation, increases mitochondrial ROS, and reduces PINK1/PARK2-dependent mitophagy.
• Pharmacological mitophagy stimulation or Vitamin C treatment rescued the developmental defects in Muc1-null embryos.

Conclusions:

• MUC1 is essential for safeguarding early embryonic development by promoting mitophagy and reducing mitochondrial ROS.
• Vitamin C can compensate for MUC1 deficiency by scavenging ROS, highlighting its potential in ART.
• This study reveals a novel mechanism for mitophagy regulation in early embryos with implications for ART therapies.