Genome Editing for Fertility: Unlocking the Promise of CRISPR/Cas9 in Addressing Male Infertility – A Narrative Review

World Health Organization. Infertility. 2024. Available at: https://www.who.int/news-room/fact-sheets/detail/infertility

Calogero AE, Cannarella R, Agarwal A, Hamoda TAA, Rambhatla A, Saleh R, et al. The renaissance of male infertility management in the golden age of andrology. World J Mens Health. 2023;41(2):237–54. https://doi.org/10.5534/wjmh.220213.

Article  PubMed  PubMed Central  Google Scholar 

World Health Organization (WHO). WHO laboratory manual for the examination and processing of human semen. 6th ed. WHO; 2021. https://iris.who.int/bitstream/handle/10665/343208/9789240030787-eng.pdf?sequence=1.

Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015;21(4):411–26. https://doi.org/10.1093/humupd/dmv016.

Article  PubMed  Google Scholar 

Gül M, Russo GI, Kandil H, Boitrelle F, Saleh R, Chung E, et al. Male infertility: new developments, current challenges, and future directions. World J Mens Health. 2024;42(3):502–17. https://doi.org/10.5534/wjmh.230232.

Article  PubMed  PubMed Central  Google Scholar 

Leslie SW, Soon-Sutton TL, Khan MAB. Male infertility. In: StatPearls. Treasure Island, FL: StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562258/

Agarwal A, Mulgund A, Hamada A, Chyatte MR. A unique view on male infertility around the Globe. Reprod Biol Endocrinol. 2015;13:37. https://doi.org/10.1186/s12958-015-0032-1.

Article  PubMed  PubMed Central  Google Scholar 

Sengupta P, Dutta S, Krajewska-Kulak E. The disappearing sperms: analysis of reports published between 1980 and 2015. Am J Mens Health. 2017;11(4):1279–304. https://doi.org/10.1177/1557988316643383.

Article  PubMed  Google Scholar 

Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Jolles M, et al. Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries. Hum Reprod Update. 2023;29(2):157–76. https://doi.org/10.1093/humupd/dmac035.

Article  PubMed  Google Scholar 

Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during the past 50 years. BMJ. 1992;305(6854):609–13. https://doi.org/10.1136/bmj.305.6854.609.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Wang HQ, Wang T, Gao F, Ren WZ. Application of crispr/cas technology in spermatogenesis research and male infertility treatment. Genes (Basel). 2022;13(6):1000. https://doi.org/10.3390/genes13061000.

Article  PubMed  CAS  Google Scholar 

Sudhakar DVS, Shah R, Gajbhiye RK. Genetics of male infertility - present and future: a narrative review. J Hum Reprod Sci. 2021;14(3):217–27. https://doi.org/10.4103/jhrs.jhrs_115_21

Article  PubMed  PubMed Central  CAS  Google Scholar 

Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol. 2018;15(6):369–84. https://doi.org/10.1038/s41585-018-0003-3.

Article  PubMed  CAS  Google Scholar 

Assidi M. Infertility in men: advances towards a comprehensive and integrative strategy for precision theranostics. Cells. 2022;11(10):1711. https://doi.org/10.3390/cells11101711.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Salas-Huetos A, Aston KI. Defining new genetic etiologies of male infertility: progress and future prospects. Transl Androl Urol. 2021;10(3):1486–98. https://doi.org/10.21037/tau.2020.03.43.

Article  PubMed  PubMed Central  Google Scholar 

Oud MS, Volozonoka L, Smits RM, Vissers LELM, Ramos L, Veltman JA. A systematic review and standardized clinical validity assessment of male infertility genes. Hum Reprod. 2019;34(5):932–41. https://doi.org/10.1093/humrep/dez022.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Joseph S, Mahale SD. Male Infertility Knowledgebase: decoding the genetic and disease landscape. Database (Oxford). 2021;2021:baab049. https://doi.org/10.1093/database/baab049

Geng H, Tang D, Li K, Xu C, Wang C, Zhang X, et al. Diverse phenotypes and fertility outcomes of patients with androgen insensitivity syndrome in a Chinese family harboring identical AR gene variant. BMC Med Genomics. 2024;17(1):249. https://doi.org/10.1186/s12920-024-01990-9.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Dieterich K, Soto Rifo R, Faure AK, Hennebicq S, Ben Amar B, Zahi M, et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet. 2007;39(5):661–5. https://doi.org/10.1038/ng2027.

Article  PubMed  CAS  Google Scholar 

Dam AH, Koscinski I, Kremer JA, Moutou C, Jaeger AS, Oudakker AR, et al. Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. Am J Hum Genet. 2007;81(4):813–20. https://doi.org/10.1086/521314.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fujihara Y, Oji A, Larasati T, Kojima-Kita K, Ikawa M. Human Globozoospermia-related gene Spata16 is required for sperm formation revealed by CRISPR/Cas9-Mediated mouse models. Int J Mol Sci. 2017;18(10):2208. https://doi.org/10.3390/ijms18102208

Article  PubMed  PubMed Central  CAS  Google Scholar 

Shang YL, Zhu FX, Yan J, Chen L, Tang WH, Xiao S, et al. Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility. Asian J Androl. 2019;21(2):183–9. https://doi.org/10.4103/aja.aja_79_18.

Article  PubMed  CAS  Google Scholar 

Xiang M, Wang Y, Wang K, Kong S, Lu M, Zhang J, et al. Novel mutation and deletion in SUN5 cause male infertility with acephalic spermatozoa syndrome. Reprod Sci. 2022;29(2):646–51. https://doi.org/10.1007/s43032-021-00665-5.

Article  PubMed  CAS  Google Scholar 

Reynolds N, Cooke HJ. Role of the DAZ genes in male fertility. Reprod Biomed Online. 2005;10(1):72–80. https://doi.org/10.1016/s1472-6483(10)60806-1.

Article  PubMed  CAS  Google Scholar 

Nongthombam PD, Malini SS. Association of DAZL polymorphisms and DAZ deletion with male infertility: a systematic review and meta-analysis. Genes Genomics. 2023;45(6):709–22. https://doi.org/10.1007/s13258-022-01345-7.

Article  PubMed  CAS  Google Scholar 

Nishiyama S, Kishi T, Kato T, Suzuki M, Bolor H, Nishizawa H, et al. A rare synaptonemal complex protein 3 gene variant in unexplained female infertility. Mol Hum Reprod. 2011;17(4):266–71. https://doi.org/10.1093/molehr/gaq098.

Article  PubMed  CAS  Google Scholar 

Junahar D, Dwiputri R, Adikusuma W, Darmawi D, Afdal A, Muhammad Irham L, et al. Potential biomarker signatures in male infertility: integrative genomic analysis. Egypt J Med Hum Genet. 2024;25:39. https://doi.org/10.1186/s43042-024-00512-7.

Article  Google Scholar 

Xie CT, Zhang HL, Li Y, Li Q, Wen YX, Liu JY, et al. Single-cell RNA-seq and pathological phenotype reveal the functional atlas and precise roles of Sox30 in testicular cell development and differentiation. Cell Death Dis. 2025;16(1):110. https://doi.org/10.1038/s41419-025-07442-1.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mullegama SV, Klein SD, Signer RH, UCLA Clinical Genomics Center, Vilain E, Martinez-Agosto JA. Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: expanding the phenotype in males. Mol Genet Genomic Med. 2019;7(2):e00501. https://doi.org/10.1002/mgg3.501.

Article  PubMed  CAS  Google Scholar 

Nam Y, Kang KM, Sung SR, Park JE, Shin YJ, Song SH, et al. The association of stromal antigen 3 (STAG3) sequence variations with spermatogenic impairment in the male Korean population. Asian J Androl. 2020;22(1):106–11. https://doi.org/10.4103/aja.aja_28_19.

Article  PubMed  CAS  Google Scholar 

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