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Fertilization with Protamine-2 deficient sperm triggers abnormal pronucleus development and zygotic cleavage†
Shannon R Rainsford1,2, Kevin Tse1,2, Benjamin William Walters1
1Department of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.
Biology of Reproduction
|January 20, 2026
Summary
Protamine 2 (Prm2) is crucial for sperm DNA condensation and fertilization. Sperm lacking Prm2 cause embryo arrest and abnormal zygotes, highlighting Prm2
Area of Science:
- Reproductive Biology
- Sperm Biology
- Developmental Biology
Background:
- Sperm DNA is condensed by protamines, essential for sperm function and fertilization.
- The role of protamine-mediated DNA condensation in oocyte reprogramming remains unclear.
Purpose of the Study:
- To investigate the impact of Protamine 2 (Prm2) deficiency on sperm function and early embryonic development.
- To understand how Prm2 affects the oocyte's ability to reprogram paternal genetic material.
Main Methods:
- Intracytoplasmic sperm injection (ICSI) using sperm lacking Protamine 2 (Prm2 KO) in mice.
- Tracking preimplantation embryonic development and analyzing zygote formation.
Main Results:
- ICSI with Prm2 KO sperm resulted in embryo fragmentation and 2-cell stage arrest.
- Prm2 KO sperm DNA was rapidly depleted from the oocyte, leading to abnormal pronuclei formation.
- Testicular Prm2 KO sperm supported blastocyst development, suggesting epididymal maturation is key.
Conclusions:
- Protamine 2 is essential for proper epididymal sperm maturation.
- Prm2 is required for the formation of a functional zygote during fertilization.
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