Intraperitoneal ZP123 improves aged oocyte quality by restoring granulosa cell gap junctions and improving...

Area of Science:

• Reproductive Biology
• Cellular Biology
• Gerontology

Background:

• Female fertility declines with age due to oocyte quality deterioration.
• Oocyte maturation relies on granulosa cell communication via connexin 43 (CX43) gap junctions.
• Age-related decline in CX43-mediated communication's impact on oocyte quality is not fully understood.

Purpose of the Study:

• To investigate age-related changes in CX43 gap junction communication in the ovary.
• To determine if the peptide ZP123 can restore CX43-mediated coupling and improve fertility in aged females.

Main Methods:

• Assessed CX43 expression and phosphorylation in aged mouse ovaries and granulosa cells.
• Evaluated ZP123 effects on gap junction communication in vitro (KGN cells) and in vivo (aged mice).
• Analyzed oocyte maturation, spindle/mitochondrial function, ATP production, ROS levels, and embryo development in ZP123-treated aged mice.

Main Results:

• CX43 expression and phosphorylation decreased with age in mouse ovaries.
• ZP123 enhanced gap junction communication, improved follicle development, and oocyte maturation rates in aged mice.
• ZP123 treatment restored mitochondrial function, reduced oxidative stress, and increased blastocyst formation rates.

Conclusions:

• Disrupted CX43-mediated communication is a key factor in age-related oocyte quality decline.
• Enhancing gap junction function with ZP123 effectively restored ovarian function and oocyte developmental potential.
• Gap junction modulation presents a novel therapeutic strategy for mitigating age-related fertility loss.