Abstract
Knockout Dnah17 rats were generated due to its potential involvement in myopia. Subsequent study suggested that the homozygous truncation variants in DNAH17 is associated with male fertility but not myopia. Sperm count and sperm motility were measured in male rats. HE staining, immunofluorescence staining and TUNEL staining were used to observe the gross and histopathology of testis in homozygous and wild rats. Dnah17 knockout rats were generated by CRISPR/Cas9 gene editing. In the process of breeding rats, homozygous male rats were noted to be infertile, with significantly decreased number of sperm suggesting cryptozoospermia that was further confirmed by histologic studies. TUNEL assay showed an increased apoptosis in homozygous testes compared with wild type (P<0.001). A significant reduction of spermatocytes was observed in homozygotes compared with wild type (P=0.025) by immunofluorescence. These results suggest that DNAH17 is critical for spermatogenesis in male rats.
Similar content being viewed by others
References
Ben Khelifa M., Coutton C., Zouari R., Karaouzene T., Rendu J., Bidart M. et al. 2014 Mutations in DNAH1, which encodes an inner arm heavy chain dynein, lead to male infertility from multiple morphological abnormalities of the sperm flagella. Am. J. Hum. Genet. 94, 95–104.
Courtade M., Lagorce C., Bujan L., Caratero C. and Mieusset R. 1998 Clinical characteristics and light and transmission electron microscopic sperm defects of infertile men with persistent unexplained asthenozoospermia. Fertil. Steril. 70, 297–304.
Coutton C., Martinez G., Kherraf Z. E., Amiri-Yekta A., Boguenet M., Saut A. et al. 2019 Bi-allelic mutations in ARMC2 lead to severe astheno-teratozoospermia due to sperm flagellum malformations in humans and mice. Am. J. Hum. Genet. 104, 331–340.
Dong F. N., Amiri-Yekta A., Martinez G., Saut A., Tek J., Stouvenel L. et al. 2018 Absence of CFAP69 causes male infertility due to multiple morphological abnormalities of the flagella in human and mouse. Am. J. Hum. Genet. 102, 636–648.
Eijpe M., Offenberg H., Jessberger R., Revenkova E. and Heyting C. 2003 Meiotic cohesin REC8 marks the axial elements of rat synaptonemal complexes before cohesins SMC1beta and SMC3. J. Cell Biol. 160, 657–670.
Gibbons I. R. 1963 Studies on the protein components of cilia from tetrahymena pyriformis. Proc. Natl. Acad. Sci. USA 50, 1002–1010.
He X., Li W., Wu H., Lv M., Liu W., Liu C. et al. 2019 Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella. J. Med. Genet. 56, 96–103.
Ji Z. Y., Sha Y. W., Ding L. and Li P. 2017 Genetic factors contributing to human primary ciliary dyskinesia and male infertility. Asian J. Androl. 19, 515–520.
Kherraf Z. E., Amiri-Yekta A., Dacheux D., Karaouzene T., Coutton C., Christou-Kent M. et al. 2018 A homozygous ancestral SVA-insertion-mediated deletion in WDR66 induces multiple morphological abnormalities of the sperm flagellum and male infertility. Am. J. Hum. Genet. 103, 400–412.
Li Y., Yagi H., Onuoha E. O., Damerla R. R., Francis R., Furutani Y. et al. 2016 DNAH6 and its interactions with PCD genes in heterotaxy and primary ciliary dyskinesia. PLoS Genet. 12, e1005821.
Li L., Sha Y. W., Xu X., Mei L. B., Qiu P. P., Ji Z. Y. et al. 2018 DNAH6 is a novel candidate gene associated with sperm head anomaly. Andrologia, https://doi.org/10.1111/and.12953.
Li W., He X., Yang S., Liu C., Wu H., Liu W. et al. 2019b Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility. J. Hum. Genet. 64, 49–54.
Li Y., Sha Y., Wang X., Ding L., Liu W., Ji Z. et al. 2019a DNAH2 is a novel candidate gene associated with multiple morphological abnormalities of the sperm flagella. Clin. Genet. 95, 590–600.
Liu C., Lv M., He X., Zhu Y., Amiri-Yekta A., Li W. et al. 2020 Homozygous mutations in SPEF2 induce multiple morphological abnormalities of the sperm flagella and male infertility. J. Med. Genet. 57, 31–37.
Liu M., Maselli J., Hales B. F. and Robaire B. 2015 The effects of chemotherapy with bleomycin, etoposide, and cis-platinum on telomeres in rat male germ cells. Andrology 3, 1104–1112.
Liu W., He X., Yang S., Zouari R., Wang J., Wu H. et al. 2019b Bi-allelic mutations in TTC21A induce asthenoteratospermia in humans and mice. Am. J. Hum. Genet. 104, 738–748.
Lores P., Coutton C., El Khouri E., Stouvenel L., Givelet M., Thomas L. et al. 2018 Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary male infertility and multiple morphological anomalies of the flagella but not to primary ciliary dyskinesia. Hum. Mol. Genet. 27, 1196–1211.
Martinez G., Kherraf Z. E., Zouari R., Fourati Ben Mustapha S., Saut A., Pernet-Gallay K. et al. 2018 Whole-exome sequencing identifies mutations in FSIP2 as a recurrent cause of multiple morphological abnormalities of the sperm flagella. Hum. Reprod. 33, 1973–1984.
Milisav I. and Affara N. A. 1998 A potential human axonemal dynein heavy-chain gene maps to 17q25. Mamm. Genome. 9, 404–407.
Pazour G. J., Agrin N., Walker B. L. and Witman G. B. 2006 Identification of predicted human outer dynein arm genes: candidates for primary ciliary dyskinesia genes. J. Med. Genet. 43, 62–73.
Sha Y. W., Xu X., Mei L. B., Li P., Su Z. Y., He X. Q. et al. 2017 A homozygous CEP135 mutation is associated with multiple morphological abnormalities of the sperm flagella (MMAF). Gene 633, 48–53.
Sha Y., Liu W., Wei X., Zhu X., Luo X., Liang L. et al. 2019a Biallelic mutations in Sperm flagellum 2 cause human multiple morphological abnormalities of the sperm flagella (MMAF) phenotype. Clin. Genet. 96, 385–393.
Sha Y. W., Wang X., Xu X., Su Z. Y., Cui Y., Mei L. B. et al. 2019b Novel mutations in CFAP44 and CFAP43 cause multiple morphological abnormalities of the sperm flagella (MMAF). Reprod. Sci. 26, 26–34.
Shen Y., Zhang F., Li F., Jiang X., Yang Y., Li X. et al. 2019 Loss-of-function mutations in QRICH2 cause male infertility with multiple morphological abnormalities of the sperm flagella. Nat. Commun. 10, 433.
Summers K. E. and Gibbons I. R. 1971 Adenosine triphosphate-induced sliding of tubules in trypsin-treated flagella of sea-urchin sperm. Proc. Natl. Acad. Sci. USA 68, 3092–3096.
Tang S., Wang X., Li W., Yang X., Li Z., Liu W. et al. 2017 Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella. Am. J. Hum. Genet. 100, 854–864.
Whitfield M., Thomas L., Bequignon E., Schmitt A., Stouvenel L., Montantin G. et al. 2019 Mutations in DNAH17, encoding a sperm-specific axonemal outer dynein arm heavy chain, cause isolated male infertility due to asthenozoospermia. Am. J. Hum. Genet. 105, 198–212.
Wilton L. J., Temple-Smith P. D. and de Kretser D. M. 1992 Quantitative ultrastructural analysis of sperm tails reveals flagellar defects associated with persistent asthenozoospermia. Hum. Reprod. 7, 510–516.
Yang Y., Cheng L., Wang Y., Han Y., Liu J., Deng X. et al. 2017 Expression of NDUFA13 in asthenozoospermia and possible pathogenesis. Reprod. Biomed. Online 34, 66–74.
Yuan L., Liu J. G., Zhao J., Brundell E., Daneholt B. and Hoog C. 2000 The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol. Cell 5, 73–83.
Yuan L., Liu J. G., Hoja M. R., Lightfoot D. A. and Hoog C. 2001 The checkpoint monitoring chromosomal pairing in male meiotic cells is p53-independent. Cell Death Differ. 8, 316–317.
Zhang B., Ma H., Khan T., Ma A., Li T., Zhang H. et al. 2019 A DNAH17 missense variant causes flagella destabilization and asthenozoospermia. J. Exp. Med. 217, e20182365.
Acknowledgements
This work was supported by grants from National Natural Science Foundation of China (81770965) and the Fundamental Research Funds of the State Key Laboratory of Ophthalmology.
Author information
Authors and Affiliations
Corresponding author
Additional information
Corresponding editor: S. Ganesh
Rights and permissions
About this article
Cite this article
Chen, L., Ouyang, J., Li, X. et al. DNAH17 is essential for rat spermatogenesis and fertility. J Genet 100, 14 (2021). https://doi.org/10.1007/s12041-021-01264-8
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12041-021-01264-8