Immunization with CENP-C Causes Aberrant Chromosome Segregation during Oocyte Meiosis in Mice

Area of Science:

• Reproductive immunology
• Cell biology
• Autoimmunity

Background:

• Anticentromere antibodies (ACA) are linked to reduced oocyte maturation and cleavage rates, but the underlying mechanisms remain unclear.
• Investigating the impact of specific autoantibodies on female reproductive processes is crucial for understanding infertility.

Purpose of the Study:

• To determine if active immunization with centromere protein C (CENP-C) can induce CENP-C autoantibodies in mice.
• To evaluate the effects of induced CENP-C autoantibodies on oocyte meiosis and identify potential mechanisms of reproductive impairment.

Main Methods:

• BALB/c mice were actively immunized with human CENP-C in Freund's adjuvant (experimental group) or Freund's adjuvant alone (control group).
• Serum and oocytes were analyzed for CENP-C antibody presence.
• Oocyte meiosis was assessed by evaluating germinal vesicle breakdown (GVBD), first polar body (Pb1) extrusion, spindle morphology, and chromosome alignment.

Main Results:

• CENP-C autoantibodies were successfully induced in the experimental group and detected in their serum and oocytes.
• The experimental group exhibited significantly lower Pb1 extrusion rates (P < 0.01).
• A higher incidence of spindle defects (64.67% vs. 9.27%) and chromosome misalignment (50.80% vs. 8.30%) was observed in the experimental group compared to controls (P < 0.01 for both).

Conclusions:

• Active immunization with CENP-C effectively elicits autoantibodies that target the oocyte.
• CENP-C autoantibodies severely impair oocyte meiosis, leading to abnormal spindle formation and chromosome segregation.
• These findings suggest that CENP-C autoantibodies may be a key factor contributing to adverse reproductive outcomes in ACA-positive women without overt autoimmune disease.