Mitochondrial Calcium Disorder Affects Early Embryonic Development in Mice through Regulating the ERK/MAPK Pathway

Area of Science:

• Reproductive Biology
• Mitochondrial Physiology
• Developmental Biology

Background:

• Mitochondrial calcium ([Ca2+]mt) homeostasis is vital for oocyte meiosis.
• The role of [Ca2+]mt in early embryonic development remains largely unexplored.

Purpose of the Study:

• To investigate the association between [Ca2+]mt homeostasis and early embryonic development in vitro.
• To elucidate the mechanisms by which [Ca2+]mt influences oocyte quality and epigenetic modifications.

Main Methods:

• Established in vitro mouse MII oocyte models using mitochondrial calcium uniporter (MCU) agonists and inhibitors.
• Assessed oocyte mitochondrial function, spindle/chromosome structure, and blastocyst development rates.
• Analyzed epigenetic modifications and mitogen-activated protein kinase (MAPK) signaling pathways.

Main Results:

• Imbalanced [Ca2+]mt led to mitochondrial dysfunction, abnormal oocyte morphology, and compromised spindle/chromosome structure.
• Oocytes with dysregulated [Ca2+]mt showed reduced blastocyst development rates in vitro.
• Abnormal [Ca2+]mt hindered epigenetic modifications and altered MAPK signaling, including MAPK/ERK regulation of DNA methylation.

Conclusions:

• [Ca2+]mt homeostasis is essential for maintaining oocyte quality and supporting successful early embryonic development.
• Dysregulation of [Ca2+]mt negatively impacts oocyte developmental potential through mitochondrial dysfunction and epigenetic alterations.
• MAPK/ERK signaling, regulated by [Ca2+]mt, plays a role in modulating DNA methylation and epigenetic modifications in MII oocytes.