Fetuin-B, a liver-derived plasma protein is essential for fertilization

Area of Science:

• Reproductive Biology
• Molecular Endocrinology
• Mammalian Reproduction

Background:

• The zona pellucida (ZP) is a critical glycoprotein matrix surrounding mammalian oocytes, essential for regulating fertilization.
• ZP hardening post-fertilization prevents polyspermy, but premature hardening can cause infertility.
• The role of plasma proteins in modulating ZP properties and fertilization remains an area of active investigation.

Purpose of the Study:

• To investigate the function of the liver-derived plasma protein fetuin-B in mammalian fertilization.
• To determine the mechanism by which fetuin-B influences zona pellucida properties.
• To establish the necessity of plasma fetuin-B for maintaining female fertility.

Main Methods:

• Targeted gene deletion of fetuin-B in mice to create deficient models.
• Ovarian transplantation experiments to assess the necessity of plasma fetuin-B.
• In vitro fertilization assays with laser perforation of the zona pellucida.
• Analysis of ovastacin activity and its interaction with fetuin-B.

Main Results:

• Fetuin-B deficiency resulted in premature zona pellucida hardening and consequent female infertility.
• Fertility was restored in fetuin-B-deficient mice upon transplantation into wild-type recipients, highlighting the role of plasma fetuin-B.
• In vitro fertilization of oocytes from deficient mice was only successful after mechanical or laser-induced zona pellucida penetration.
• Fetuin-B was found to inhibit ovastacin, a protease responsible for triggering zona pellucida hardening.

Conclusions:

• Plasma fetuin-B is essential for maintaining female fertility by preventing premature zona pellucida hardening.
• Fetuin-B acts by inhibiting the protease ovastacin, thereby regulating zona pellucida permeability until after gamete fusion.
• These findings reveal a novel mechanism regulating fertilization and identify premature ZP hardening as a cause of infertility.