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Updated: Sep 2, 2025

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Human-specific gene CT47 blocks PRMT5 degradation to lead to meiosis arrest

Chao Li1, Yuming Feng2, Zhenxin Fu1

  • 1Cambridge-Su Genomic Resource Center, Jiangsu Key Laboratory of Neuropsychiatric Diseases, Medical School of Soochow University, Suzhou, Jiangsu, 215123, China.

Cell Death Discovery
|August 2, 2022
PubMed

Insights

Cancer/Testis Antigen gene family 47 (CT47) is vital for human spermatogenesis, preventing early meiosis. Testosterone depletion of CT47/PRMT5 rescues arrested cells, crucial for male fertility.

Area of Science:

  • Reproductive Biology
  • Genetics
  • Molecular Endocrinology

Background:

  • Human-specific genes (HSGs) present challenges in functional studies due to limited model systems.
  • Testosterone is critical for human spermatogenesis and fertility, but its precise molecular mechanisms remain incompletely understood.

Purpose of the Study:

  • To identify key regulators of human-specific spermatogenesis.
  • To elucidate the mechanism by which testosterone influences male fertility.

Main Methods:

  • Identified Cancer/Testis Antigen gene family 47 (CT47) as a regulator of human spermatogenesis.
  • Utilized a humanized mouse model to study CT47 function in vivo.
  • Employed CRISPR/Cas9 in human embryonic stem cells (hESCs) to investigate CT47's role in haploid cell differentiation.
  • Analyzed CT47 expression levels in patients with nonobstructive azoospermia.

Main Results:

  • CT47 stabilizes arginine methyltransferase 5 (PRMT5), regulating spermatogenesis.
  • CT47/PRMT5 nuclear accumulation during meiosis arrest can be reversed by testosterone.
  • Loss of CT47 in hESCs disrupts testosterone-mediated haploid cell production.
  • Reduced CT47 levels correlate with nonobstructive azoospermia.

Conclusions:

  • CT47 is a critical regulator of human spermatogenesis, preventing premature meiosis initiation.
  • Testosterone signaling modulates CT47/PRMT5 activity to permit progression of spermatogenesis.
  • CT47 dysfunction may contribute to male infertility, specifically nonobstructive azoospermia.

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