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Polyglutamine-binding protein 1 protects mouse testes from heat stress.

Meng Lv1, Haiquan Wang2, Danyang Chong3

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.

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Testicular heat stress impairs sperm production by disrupting cellular stress granules. The RNA-binding protein PQBP1 is crucial for forming these granules, safeguarding male fertility.

Keywords:
Heat stressMale infertilitySperm functionStress granule

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Area of Science:

  • Reproductive biology
  • Cellular stress response
  • Molecular mechanisms of infertility

Background:

  • Testicular heat exposure, from fever or undescended testes, causes male infertility by damaging sperm production.
  • Cells form stress granules, RNA-protein complexes, to protect themselves from stress.
  • The role of Polyglutamine binding protein 1 (PQBP1) in testicular thermal stress response was unknown.

Purpose of the Study:

  • To investigate the role of PQBP1 in testicular heat stress.
  • To determine if PQBP1 regulates stress granule formation in germ cells.
  • To understand the impact of PQBP1 deficiency on sperm function under heat stress.

Main Methods:

  • Utilized a mouse model with a Pqbp1 Y65C mutation.
  • Exposed mice to heat stress and analyzed testicular tissue.
  • Assessed stress granule assembly, sperm motility, and gene expression profiles.

Main Results:

  • Mutant mice showed impaired stress granule assembly in testes after heat exposure.
  • Heat-stressed mutant testes had significantly reduced sperm motility.
  • Transcriptomic analysis revealed increased inflammation and cellular stress in mutant testes.

Conclusions:

  • PQBP1 is essential for orchestrating the stress granule response during testicular heat stress.
  • PQBP1 deficiency leads to defective germ cell homeostasis and impaired sperm function.
  • Targeting the stress granule pathway may offer a therapeutic strategy for heat-induced male infertility.