Tdrd6, or Tudor containing protein 6, is a male germ line-specific protein crucial for male fertility. It is essential for chromatoid body (ChB) structure and spermiogenesis, and is involved in pathways such as nonsense-mediated mRNA decay and spliceosome maturation [1,3,5]. Genetic models like knockout mice are valuable for studying Tdrd6's functions.

In Tdrd6-deficient mice, spermatogenesis is blocked at the round spermatid stage, with disrupted ChB architecture. The assembly of proteins like PIWIL1, TDRD1, TDRD7, and DDX25 in ChBs is disturbed [2]. Tdrd6-knockout mice also exhibit splicing defects in prophase I spermatocytes, with impaired spliceosome maturation, reduced levels of U5 snRNPs, and decreased numbers of SMN-positive bodies and Cajal bodies [1]. Additionally, Tdrd6 deficiency affects the localization of NMD machinery components like UPF1 to ChBs and impairs the long 3' UTR-triggered NMD pathway [5].

In conclusion, Tdrd6 is essential for spermiogenesis, ChB structure, mRNA splicing, and the regulation of miRNA and mRNA expression. Studies using Tdrd6-knockout mouse models have revealed its critical role in male infertility, particularly in cases of severe oligo-astheno-teratozoospermia, providing insights into potential genetic diagnostic targets for male infertility [1,2,3,4].

References:

1. Akpınar, Müge, Lesche, Mathias, Fanourgakis, Grigorios, Dahl, Andreas, Jessberger, Rolf. 2017. TDRD6 mediates early steps of spliceosome maturation in primary spermatocytes. In PLoS genetics, 13, e1006660. doi:10.1371/journal.pgen.1006660. https://pubmed.ncbi.nlm.nih.gov/28263986/

2. Bi, Xinying, Jin, Huijuan, Wan, Feng, Chen, Suren, Wang, Binbin. . Loss-of-function variant in TDRD6 cause male infertility with severe oligo-astheno-teratozoospermia in human and mice. In Journal of cellular and molecular medicine, 28, e18580. doi:10.1111/jcmm.18580. https://pubmed.ncbi.nlm.nih.gov/39331689/

3. Vasileva, Ana, Tiedau, Daniela, Firooznia, Adriana, Müller-Reichert, Thomas, Jessberger, Rolf. 2009. Tdrd6 is required for spermiogenesis, chromatoid body architecture, and regulation of miRNA expression. In Current biology : CB, 19, 630-9. doi:10.1016/j.cub.2009.02.047. https://pubmed.ncbi.nlm.nih.gov/19345099/

4. Guo, Rui, Wu, Huan, Zhu, Xiaoyu, Cao, Yunxia, He, Xiaojin. 2024. Bi-allelic variants in chromatoid body protein TDRD6 cause spermiogenesis defects and severe oligoasthenoteratozoospermia in humans. In Journal of medical genetics, 61, 553-565. doi:10.1136/jmg-2023-109766. https://pubmed.ncbi.nlm.nih.gov/38341271/

5. Fanourgakis, Grigorios, Lesche, Mathias, Akpinar, Müge, Dahl, Andreas, Jessberger, Rolf. 2016. Chromatoid Body Protein TDRD6 Supports Long 3' UTR Triggered Nonsense Mediated mRNA Decay. In PLoS genetics, 12, e1005857. doi:10.1371/journal.pgen.1005857. https://pubmed.ncbi.nlm.nih.gov/27149095/