Impaired sperm maturation in RNASE9 knockout mice

Area of Science:

• Reproductive biology
• Molecular and cellular biology
• Biochemistry

Background:

• Ribonuclease 9 (RNASE9) is a secreted protein found exclusively in the epididymis.
• Despite lacking ribonuclease activity, its epididymis-specific expression suggests a role in sperm maturation.
• The precise function of RNASE9 in male reproduction remains largely unknown.

Purpose of the Study:

• To investigate the in vivo function of RNASE9 using a knockout mouse model.
• To determine the role of RNASE9 in sperm maturation, fertility, and associated signaling pathways.

Main Methods:

• Generation and analysis of RNASE9-deficient (Rnase9(-/-)) mice.
• Assessment of sperm morphology, motility, and fertilization rates (in vitro and in vivo).
• Analysis of capacitation-dependent signaling pathways, including protein phosphorylation.

Main Results:

• RNASE9 expression is confirmed to be restricted to the epididymis, with specific temporal and spatial patterns.
• Rnase9(-/-) mice exhibit normal fertility, spermatogenesis, and sperm morphology.
• A significant impairment in sperm motility was observed in Rnase9(-/-) mice shortly after isolation, linked to decreased phosphorylation of protein kinase A substrates during capacitation.

Conclusions:

• RNASE9 is not essential for male fertility.
• Absence of RNASE9 during epididymal transit leads to impaired sperm maturation, specifically affecting motility and capacitation signaling.
• RNASE9 plays a crucial, albeit non-essential for fertility, role in optimizing sperm function post-ejaculation.