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Spermatozoa lacking TEX51 display hypofertility and defects in morphology.
Sophie Dupuis1, Morgane Le Beulze1, Tyler D R Vance2
1Institut Cochin, CNRS, INSERM, Université Paris Cité, Paris, France.
Communications Biology
|November 13, 2025
Summary
Researchers identified TEX51 as a new member of the IST superfamily, crucial for fertilization. Tex51-knockout mice showed infertility and sperm defects, revealing its role in sperm formation.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- Fertilization is vital for reproduction, but its molecular mechanisms are not fully understood.
- The IST (Infertility and Spermatogenesis Target) superfamily proteins are key players in fertilization.
- Previous research has identified IZUMO1, SPACA6, and TMEM95 within this family.
Purpose of the Study:
- To identify novel IST superfamily members using structure-based proteome searches.
- To investigate the function of the newly identified protein TEX51 in mammalian fertilization.
- To elucidate the role of TEX51 in sperm development and male fertility.
Main Methods:
- Structure-based search of the AlphaFold human proteome to identify potential IST superfamily members.
- Bioinformatic analysis of TEX51 structure, expression, and conservation.
- Generation and analysis of a Tex51-knockout (KO) mouse model.
- In vivo and in vitro fertility assessments, sperm motility analysis, and electron microscopy.
Main Results:
- TEX51 was identified as a novel IST superfamily protein with structural similarities to known members.
- Tex51-KO male mice exhibited hypofertitily despite normal sperm motility.
- KO sperm displayed morphological abnormalities, including flagellar disjunction, cytoplasmic remnants, and acrosome-nucleus anchoring defects.
Conclusions:
- TEX51 plays a critical role in mammalian male fertility.
- The IST superfamily's function extends beyond gamete interaction to sperm formation during spermiogenesis.
- TEX51 is essential for proper sperm morphology and development, impacting reproductive success.
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