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Defective maturation: Abnormal DNA repair
• In normal spermiogenesis, transient DNA breaks are introduced
 Transient relieve torsional stress of DNA and remove DNA supercoiling;
 Facilitate histone to protamine exchange.
• These temporary breaks if not repaired, lead to DNA
fragmentation.
• Mice deficient for poly(ADP‐ribose) polymerase have a high level of unrepaired DNA nicks and male infertility (Meyer‐ Ficca et al. 2009).
Meyer‐Ficca et al (2009) Biol Reprod. 8(1):46–55.
Reactive oxygen species (ROS) is required for normal sperm function
• Spermatozoa generate ROS by
– Mitochondria: NADH‐dependent oxido‐reductase (diphorase).
NADPH oxidase system at plasma membrane
• Low levels are required for capacitation, zona pellucida binding, hyperactivation, acrosome reaction and oocyte fusion
Histone solenoids Protamine toroids Protamine‐S‐S‐Protamine
snGPx4 + ROS (H2O2)
snGPx4 = sperm nucleus glutathione peroxidase 4
Epididymal transit
Sngpx4 null mice : abnormal post‐testicular nuclear compaction.
Champroux et al. (2016) Basic and Clinical Andrology (2016) 26:17
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