The Telomerase RNA Protein TERP Exerts a New Function in Safeguarding Female Gamete Quality

Area of Science:

• Reproductive Biology
• Molecular Genetics

Background:

• Oocyte quality is essential for female fertility, yet its molecular regulation is not fully understood.
• The specific role of telomerase RNA protein (TERP) in oogenesis remains unexplored.

Purpose of the Study:

• To investigate the non-canonical function of TERP in maintaining female gamete quality.
• To elucidate the molecular mechanisms by which TERP influences oocyte maturation and fertility.

Main Methods:

• Utilized gain-of-function (AT) and loss-of-function (D7) mouse models.
• Performed morphological and molecular analyses of oocytes, including immunofluorescence for meiotic spindles and Western blotting for autophagy markers.
• Quantified perinatal ovarian reserve using qRT-PCR.

Main Results:

• Both AT and D7 mutations induced significant meiotic spindle abnormalities.
• Loss of TERP function (D7) impaired cytoplasmic maturation and reduced oocyte autophagy.
• TERP deficiency led to an enlarged ovarian reserve and decreased autophagy/lysosomal markers in newborn ovaries.

Conclusions:

• TERP has a novel, non-canonical function critical for regulating oocyte quality.
• TERP dysregulation negatively impacts meiotic integrity and oocyte maturation.
• Disruption of lysosome-dependent autophagy by TERP underlies compromised female gamete quality.