Abnormal zona pellucida and follicular development in ZP1-mutant macaques

Area of Science:

• Reproductive Biology
• Genetics
• Primate Models

Background:

• Zona pellucida glycoprotein-1 (ZP1) is vital for oocyte integrity and fertilization.
• Mutations in ZP1 cause primary infertility, including fertilization failure and empty follicle syndrome.
• Lack of accurate models hinders understanding of ZP1-related infertility mechanisms.

Purpose of the Study:

• To establish the first non-human primate model for ZP1-related infertility.
• To investigate the functional role of ZP1 in primate folliculogenesis and oocyte development.
• To provide a platform for studying ZP1 gene mutations and developing infertility interventions.

Main Methods:

• CRISPR/Cas9 genome editing to generate ZP1-knockout cynomolgus macaques.
• Superovulation and oocyte retrieval from ZP1-edited female macaques.
• Immunofluorescence, transmission electron microscopy, transcriptomic profiling, and histopathology.

Main Results:

• ZP1-knockout macaques exhibited increased zona pellucida-deficient oocytes and reduced maturation rates.
• Disrupted folliculogenesis and oocyte anomalies were observed, mirroring human empty follicle syndrome.
• The study successfully created a non-human primate model for ZP1-related infertility.

Conclusions:

• The ZP1-knockout macaque is the first non-human primate model for ZP1-related infertility.
• This model elucidates disease mechanisms and aids in developing targeted interventions for ZP-gene mutation-induced infertility.
• The findings offer insights into human infertility conditions linked to ZP1 dysfunction.