Deficiency of the Tmem232 Gene Causes Male Infertility with Morphological Abnormalities of the Sperm Flagellum in Mice

Cells. 2023 Jun 13;12(12):1614. doi: 10.3390/cells12121614.

Abstract

The axoneme and accessory structures of flagella are critical for sperm motility and male fertilization. Sperm production needs precise and highly ordered gene expression to initiate and sustain the many cellular processes that result in mature spermatozoa. Here, we identified a testis enriched gene transmembrane protein 232 (Tmem232), which is essential for the structural integrity of the spermatozoa flagella axoneme. Tmem232 knockout mice were generated for in vivo analyses of its functions in spermatogenesis. Phenotypic analysis showed that deletion of Tmem232 in mice causes male-specific infertility. Transmission electron microscopy together with scanning electron microscopy were applied to analyze the spermatozoa flagella and it was observed that the lack of TMEM232 caused failure of the cytoplasm removal and the absence of the 7th outer microtubule doublet with its corresponding outer dense fiber (ODF). Co-IP assays further identified that TMEM232 interacts with ODF family protein ODF1, which is essential to maintain sperm motility. In conclusion, our findings indicate that TMEM232 is a critical protein for male fertility and sperm motility by regulating sperm cytoplasm removal and maintaining axoneme integrity.

Keywords: ODF1; TMEM232; axoneme; cytoplasm removal; sperm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Infertility, Male* / genetics
  • Infertility, Male* / metabolism
  • Male
  • Membrane Proteins* / deficiency
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Knockout
  • Semen
  • Sperm Motility* / genetics
  • Sperm Tail* / metabolism

Substances

  • Odf1 protein, mouse
  • Membrane Proteins

Grants and funding

This work was funded by the National Key R&D Program of China (2022YFC2702600), Academic Promotion Programme of Shandong First Medical University (2019U001), Basic Science Center Program of NFSC (31988101), A fund from A-Smart Group to support CUHK-SDU Joint Laboratory on Reproductive Genetics of CUHK, Major Innovation Projects in Shandong Province (2021ZDSYS16) and the Science Foundation for Distinguished Young Scholars of Shandong (ZR2021JQ27), Taishan Scholars Program for Young Experts of Shandong Province (tsqn202103192).