Study on the role of \(\textit{TDRD1}\) variants in male infertility among 310 Vietnamese individuals

La Duc Duy, Nguyen Minh Nguyet, Huynh Thi Thu Hue, Nguyen Thuy Duong
Author affiliations


  • La Duc Duy Institute of Genome Research, VAST, Vietnam
  • Nguyen Minh Nguyet Institute of Genome Research, VAST, Vietnam
  • Huynh Thi Thu Hue Institute of Genome Research, VAST, Vietnam
  • Nguyen Thuy Duong Institute of Genome Research, Vietnam Academy of Science and Technology



male infertility, PCR-RFLP, rs541192490, rs77559927, TDRD1, Vietnam


Infertility is a global reproductive health burden affected by various genetic factors, including spermatogenic defects. The instability of the germ cells’ genome caused by the unregulated replication of transposable elements is one of the causes of spermatogenic impairment. Tudor domain-containing 1 (TDRD1) expressed only in germ cells plays a significant role in the piRNA (PIWI-interacting RNA) pathway to maintain genome integrity via suppressing transposon elements during spermatogenesis. Despite the protein’s role in male germline development, TDRD1 has not been studied intensively. In this study, we established the relationship between male infertility and single nucleotide polymorphisms (SNPs) of TDRD1 (rs541192490, rs77559927) among 310 Vietnamese men (160 infertile patients and 150 healthy controls). Genotypes of single nucleotide polymorphisms of the TDRD1 gene (SNPs) were identified using the PCR-RFLP method. The results showed that TDRD1 SNPs were not associated with male infertility in all three test models (additive, dominant, and recessive) (p-value > 0.05). Haplotype analysis of the two SNPs also showed similar findings. This study would contribute to the knowledge of TDRD1’s association with male infertility in the Vietnamese population.


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Anawalt B. D., 2013. Approach to male infertility and induction of spermatogenesis. J. Clin. Endocrinol. Metab., 98: 3532–42. 10.1210/jc.2012-2400 10.1210/jc.2012-2400">

Arafat M., Har-Vardi I., Harlev A., Levitas E., Zeadna A., Abofoul-Azab M., Dyomin V., Sheffield V.C., Lunenfeld E., Huleihel M., Parvari R., 2017. Mutation in TDRD9 causes non-obstructive azoospermia in infertile men. J. Med. Genet., 54: 633–639.">

Aragon T. J., 2020. Epitools: Epidemiology Tools. epitools.

Aravin A., Gaidatzis D., Pfeffer S., Lagos-Quintana M., Landgraf P., Iovino N., Morris P., Brownstein M. J., Kuramochi-Miyagawa S., Nakano T., Chien M., Russo J. J., Ju J., Sheridan R., Sander C., Zavolan M., Tuschl T., 2006. A novel class of small RNAs bind to MILI protein in mouse testes. Nature, 442: 203–7.">

Aravin A. A., Sachidanandam R., Bourc’his D., Schaefer C., Pezic D., Toth K. F., Bestor T., Hannon G. J., 2008. A piRNA Pathway Primed by Individual Transposons Is Linked to De Novo DNA Methylation in Mice. Mol. Cell, 31:


Babakhanzadeh E., Khodadadian A., Rostami S., Alipourfard I., Aghaei M., Nazari M., Hosseinnia M., Mehrjardi M. Y. V., Jamshidi Y., Ghasemi N., 2020. Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia. BMC Med. Genet: 21. S12881-020-0970-0 S12881-020-0970-0">

Chuma S., Hosokawa M., Kitamura K., Kasai S., Fujioka M., Hiyoshi M., Takamune K., Noce T., Nakatsuji N., 2006. Tdrd1/Mtr-1, a tudor-related gene, is essential for male germ-cell differentiation and nuage/germinal granule formation in mice. Proc. Natl. Acad. Sci. U. S. A., 103: 15894–9.">

Cooke H. J., Saunders P. T. K., 2002. Mouse models of male infertility. Nat. Rev. Genet., 3: 790–801. 10.1038/nrg911 10.1038/nrg911">

Gou L. T., Kang J. Y., Dai P., Wang X., Li F., Zhao S., Zhang M., Hua M. M., Lu Y., Zhu Y., Li Z., Chen H., Wu L. G., Li D., Fu X. D., Li J., Shi H. J., Liu M. F., 2017. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis. Cell, 169:

–1104. j.cell.2017.04.034 j.cell.2017.04.034">

Graffelman J., 2015. Exploring diallelic genetic markers: The HardyWeinberg package. J. Stat. Softw., 64: 1–23.">

Gu A., Ji G., Shi X., Long Y., Xia Y., Song L., Wang S., Wang X., 2010. Genetic variants in Piwi-interacting RNA pathway genes confer susceptibility to spermatogenic failure in a Chinese population. Hum. Reprod., 25: 2955–61.">

Hirsh A., 2003. Male subfertility. BMJ, 327: 669–72. bmj.327.7416.669 bmj.327.7416.669">

Kamaliyan Z., Pouriamanesh S., Soosanabadi M., Gholami M., Mirfakhraie R., 2018. Investigation of piwi-interacting RNA pathway genes role in idiopathic non-obstructive azoospermia. Sci. Rep: 8.">

Kim Y., Choi S. J., Choi C., 2017. An efficient PCR-RFLP method for the rapid identification of Korean pyropia species. Molecules, 22: 2182. 10.3390/molecules22122182 10.3390/molecules22122182">

Klattenhoff C., Theurkauf W., 2008. Biogenesis and germline functions of piRNAs. Development, 135: 3–9.">

Kohlrausch F. B., Berteli T. S., Wang F., Navarro P. A., Keefe D. L., 2022. Control of LINE-1 Expression Maintains Genome Integrity in Germline and Early Embryo Development. Reprod. Sci., 29: 328–340.">

Kosova G., Scott N. M., Niederberger C., Prins G. S., Ober C., 2012. Genome-wide association study identifies candidate genes for male fertility traits in humans. Am. J. Hum. Genet., 90: 950–61.">

Krausz C., Escamilla A. R., Chianese C., 2015. Genetics of male infertility: From research to clinic. Reproduction, 150: R159–R174.">

Lander E. S., Linton L. M., Birren B., Nusbaum C., Zody M. C., Baldwin J., Devon K., Dewar K., Doyle M., Fitzhugh W., Funke R., Gage D., Harris K., Heaford A., Howland J., Kann L., Lehoczky J., Levine R., McEwan P., McKernan K., Meldrim J., Mesirov J.P., Miranda C., Morris W., Naylor J., Raymond C., Rosetti M., Santos R., Sheridan A., Sougnez C., Stange-Thomann N., Stojanovic N., Subramanian A., Wyman D., Rogers J., Sulston J., Ainscough R., Beck S., Bentley D., Burton J., Clee C., Carter N., Coulson A., Deadman R., Deloukas P., Dunham A., Dunham I., Durbin R., French L., Grafham D., Gregory S., Hubbard T., Humphray S., Hunt A., Jones M., Lloyd C., McMurray A., Matthews L., Mercer S., Milne S., Mullikin J. C., Mungall A., Plumb R., Ross M., Shownkeen R., Sims S., Waterston R. H., Wilson R. K., Hillier L. W., McPherson J. D., Marra M. A., Mardis E. R., Fulton L. A., Chinwalla A. T., Pepin K. H., Gish W. R., Chissoe S. L., Wendl M. C., Delehaunty K. D., Miner T. L., Delehaunty A., Kramer J. B., Cook L. L., Fulton R. S., Johnson D. L., Minx P. J., Clifton S. W., Hawkins T., Branscomb E., Predki P., Richardson P., Wenning S., Slezak T., Doggett N., Cheng J. F., Olsen A., Lucas S., Elkin C., Uberbacher E., Frazier M., Gibbs R. A., Muzny D. M., Scherer S. E., Bouck J. B., Sodergren E. J., Worley K. C., Rives C. M., Gorrell J. H., Metzker M. L., Naylor S. L., Kucherlapati R. S., Nelson D. L., Weinstock G. M., Sakaki Y., Fujiyama A., Hattori M., Yada T., Toyoda A., Itoh T., Kawagoe C., Watanabe H., Totoki Y., Taylor T., Weissenbach J., Heilig R., Saurin W., Artiguenave F., Brottier P., Bruls T., Pelletier E., Robert C., Wincker P., Rosenthal A., Platzer M., Nyakatura G., Taudien S., Rump A., Smith D. R., Doucette-Stamm L., Rubenfield M., Weinstock K., Hong M. L., Dubois J., Yang H., Yu J., Wang J., Huang G., Gu J., Hood L., Rowen L., Madan A., Qin S., Davis R. W., Federspiel N. A., Abola A. P., Proctor M. J., Roe B. A., Chen F., Pan H., Ramser J., Lehrach H., Reinhardt R., McCombie W. R., De La Bastide M., Dedhia N., Blöcker H., Hornischer K., Nordsiek G., Agarwala R., Aravind L., Bailey J. A., Bateman A., Batzoglou S., Birney E., Bork P., Brown D. G., Burge C. B., Cerutti L., Chen H. C., Church D., Clamp M., Copley R. R., Doerks T., Eddy S. R., Eichler E. E., Furey T. S., Galagan J., Gilbert J. G. R., Harmon C., Hayashizaki Y., Haussler D., Hermjakob H., Hokamp K., Jang W., Johnson L. S., Jones T.A., Kasif S., Kaspryzk A., Kennedy S., Kent W.J., Kitts P., Koonin E. V., Korf I., Kulp D., Lancet D., Lowe T.M., McLysaght A., Mikkelsen T., Moran J. V., Mulder N., Pollara V.J., Ponting C. P., Schuler G., Schultz J., Slater G., Smit A. F. A., Stupka E., Szustakowki J., Thierry-Mieg D., Thierry-Mieg J., Wagner L., Wallis J., Wheeler R., Williams A., Wolf Y. I., Wolfe K. H., Yang S. P., Yeh R. F., Collins F., Guyer M. S., Peterson J., Felsenfeld A., Wetterstrand K. A., Myers R. M., Schmutz J., Dickson M., Grimwood J., Cox D. R., Olson M. V., Kaul R., Raymond C., Shimizu N., Kawasaki K., Minoshima S., Evans G. A., Athanasiou M., Schultz R., Patrinos A., Morgan M. J., 2001. Initial sequencing and analysis of the human genome. Nature, 409:


Lau N. C., Seto A. G., Kim J., Kuramochi-Miyagawa S., Nakano T., Bartel D. P., Kingston R. E., 2006. Characterization of the piRNA complex from rat testes. Science, 313: 363–7.">

O’Bryan M. K., De Kretser D., Ivell R., Skakkebæk N. E., Almstrup K., Leffers H., 2006. Mouse models for genes involved in impaired spermatogenesis. International Journal of Andrology, 29: 76–89.">

Pandey R. R., Tokuzawa Y., Yang Z., Hayashi E., Ichisaka T., Kajita S., Asano Y., Kunieda T., Sachidanandam R., Chuma S., Yamanaka S., Pillai R.S., 2013. Tudor domain containing 12 (TDRD12) is essential for secondary PIWI interacting RNA biogenesis in mice. Proc. Natl. Acad. Sci. U. S. A., 110: 16492–7.">

Pillai R. S., Chuma S., 2012. piRNAs and their involvement in male germline development in mice. Dev. Growth Differ., 54: 78–92. 10.1111/J.1440-169X.2011.01320.X 10.1111/J.1440-169X.2011.01320.X">

R Core Team, 2020. R: A language and environment for statistical computing. Available at">

Reuter M., Chuma S., Tanaka T., Franz T., Stark A., Pillai R. S., 2009. Loss of the Mili-interacting Tudor domain-containing protein-1 activates transposons and alters the Mili-associated small RNA profile. Nat. Struct. Mol. Biol., 16: 639–46.">

Sharlip I. D., Jarow J. P., Belker A. M., Lipshultz L. I., Sigman M., Thomas A. J., Schlegel P. N., Howards S. S., Nehra A., Damewood M. D., Overstreet J. W., Sadovsky R., 2002. Best practice policies for male infertility. Fertil. Steril., 77:


Shoji M., Tanaka T., Hosokawa M., Reuter M., Stark A., Kato Y., Kondoh G., Okawa K., Chujo T., Suzuki T., Hata K., Martin S. L., Noce T., Kuramochi-Miyagawa S., Nakano T., Sasaki H., Pillai R. S., Nakatsuji N., Chuma S., 2009. The TDRD9-MIWI2 Complex Is Essential for piRNA-Mediated Retrotransposon Silencing in the Mouse Male Germline. Dev. Cell, 17: 775–87. 10.1016/j.devcel.2009.10.012 10.1016/j.devcel.2009.10.012">

Slotkin R. K., Martienssen R., 2007. Transposable elements and the epigenetic regulation of the genome. Nat. Rev. Genet., 8: 272–85.">

Yabuta Y., Ohta H., Abe T., Kurimoto K., Chuma S., Saitou M., 2011. TDRD5 is required for retrotransposon silencing, chromatoid body assembly, and spermiogenesis in mice. J. Cell Biol., 192: 781–95.">

Yadav R. P., Kotaja N., 2014. Small RNAs in spermatogenesis. Mol. Cell. Endocrinol., 382: 498–508. j.mce.2013.04.015 j.mce.2013.04.015">

Yan W., 2009. Male infertility caused by spermiogenic defects: Lessons from gene knockouts. Mol. Cell. Endocrinol., 306: 24.">

Zhu X. Bin, Lu J. Q., Zhi E. L., Zhu Y., Zou S. S., Zhu Z. J., Zhang F., Li Z., 2016. Association of a TDRD1 variant with spermatogenic failure susceptibility in the Han Chinese. J. Assist. Reprod. Genet., 33: 1099.">




How to Cite

Duc Duy, L., Minh Nguyet, N., Thi Thu Hue, H., & Thuy Duong, N. (2023). Study on the role of \(\textit{TDRD1}\) variants in male infertility among 310 Vietnamese individuals. Academia Journal of Biology, 45(2), 9–17.




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