PLCζ disruption with complete fertilization failure in normozoospermia

Area of Science:

• Reproductive Biology
• Molecular Genetics
• Assisted Reproductive Technology

Background:

• Intracytoplasmic sperm injection (ICSI) is a key treatment for male factor infertility.
• Complete fertilization failure post-ICSI affects 1-3% of couples.
• Assisted oocyte activation (AOA) is an option for fertilization failures.

Observation:

• A normozoospermic male with a history of natural conception experienced repeated fertilization failures with donor oocytes after ICSI.
• Molecular analysis revealed significantly disrupted phospholipase C zeta (PLCζ) expression and distribution in the patient's sperm.
• Functional testing using mouse oocytes (MOAT and MOCA) did not indicate a reduced oocyte activation ability.

Findings:

• Disrupted PLCζ expression and distribution in normozoospermic males can lead to fertilization failure post-ICSI.
• Functional assessments using mouse oocytes may not accurately reflect human oocyte activation potential.
• Alterations in PLCζ protein, not solely gene mutations, can cause activation failures.

Implications:

• This case highlights the complexity of diagnosing fertilization issues in ICSI.
• Further investigation into molecular and functional discrepancies of PLCζ is warranted.
• Understanding PLCζ variations is crucial for improving AOA strategies and ICSI outcomes.