Paxillin knockout in mouse granulosa cells increases fecundity†.

Area of Science:

• Reproductive biology
• Cellular biology
• Molecular genetics

Background:

• Paxillin is an intracellular adaptor protein crucial for cellular functions including focal adhesions, stress response, steroid signaling, and apoptosis.
• Its specific role in granulosa cells, which are vital for ovarian function, remained largely unexplored.

Purpose of the Study:

• To investigate the function of paxillin in granulosa cells and its impact on female fertility.
• To determine if targeting paxillin could offer strategies for managing age-related subfertility.

Main Methods:

• Generation of a granulosa-specific paxillin knockout mouse model using Cre-lox technology driven by the Anti-Müllerian hormone receptor 2 promoter.
• Assessment of fertility parameters, estrous cycles, ovarian follicle counts, and hormone levels in knockout mice.
• In vitro studies using CRISPR-Cas9 to knock out paxillin in human KGN cells and primary mouse granulosa cells to evaluate cell proliferation, migration, and death.

Main Results:

• Granulosa-specific paxillin knockout mice exhibited increased fertility in later reproductive age, characterized by shorter time to pregnancy and more litters.
• No significant changes were observed in estrous cycle frequency, oocytes ovulated per cycle, or pups per litter.
• While ovarian follicle numbers were unaffected, knockout mice showed slightly altered estrous cycles and no changes in reproductive hormone levels.
• In vitro, paxillin knockout reduced cell death in primary mouse granulosa cells but did not affect proliferation or migration in KGN cells.

Conclusions:

• Paxillin knockout in granulosa cells enhances female fecundity in aging mice, potentially by decreasing granulosa cell apoptosis.
• These findings highlight paxillin and its associated signaling pathways as potential therapeutic targets for age-related subfertility.