Abstract
Purpose
Male infertility manifests in the form of a reduction in sperm count, sperm motility, or the loss of fertilizing ability. While the loss of sperm production can have mixed reasons, sperm structural defects, cumulatively known as teratozoospermia, have predominantly genetic bases. The aim of the present review is to undertake a comprehensive analysis of the genetic mutations leading to sperm morphological deformities/teratozoospermia.
Methods
We undertook literature review for genes involved in sperm morphological abnormalities. The genes were classified according to the type of sperm defects they cause and on the basis of the level of evidence determined by the number of human studies and the availability of a mouse knockout.
Results
Mutations in the SUN5, CEP112, BRDT, DNAH6, PMFBP1, TSGA10, and SPATA20 genes result in acephalic sperm; mutations in the DPY19L2, SPATA16, PICK1, CCNB3, CHPT1, PIWIL4, and TDRD9 genes cause globozoospermia; mutations in the AURKC gene cause macrozoospermia; mutations in the WDR12 gene cause tapered sperm head; mutations in the RNF220 and ADCY10 genes result in small sperm head; mutations in the AMZ2 gene lead to vacuolated head formation; mutations in the CC2D1B and KIAA1210 genes lead to pyriform head formation; mutations in the SEPT14, ZPBP1, FBXO43, ZCWPW1, KATNAL2, PNLDC1, and CCIN genes cause amorphous head; mutations in the SEPT12, RBMX, and ACTL7A genes cause deformed acrosome formation; mutations in the DNAH1, DNAH2, DNAH6, DNAH17, FSIP2, CFAP43, AK7, CHAP251, CFAP65, ARMC2 and several other genes result in multiple morphological abnormalities of sperm flagella (MMAF).
Conclusions
Altogether, mutations in 31 genes have been reported to cause head defects and mutations in 62 genes are known to cause sperm tail defects.
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Data availability
All representative data are provided within the manuscript.
Code availability
Not applicable.
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Acknowledgements
The authors are thankful to the Council of Scientific and Industrial Research (CSIR) for funding this study under MLP2026. Poonam Mehta and Shruti Sethi would like to thank the University Grants Commission (460/CSIR-UGC NET DEC.2017 and 191620102885/CSIR-UGC NET DEC.2019, respectively), for graduate fellowships. This manuscript bears CDRI communication number 10812.
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MA, PM, and SR conceptualized and wrote the article. PM prepared the figures. SS participated in data sorting, preparing tables, and editing and revising the manuscript. GA and MS edited the manuscript. SR supervised writing, editing, and revising the manuscript. All authors have approved the final version of the manuscript.
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Arora, M., Mehta, P., Sethi, S. et al. Genetic etiological spectrum of sperm morphological abnormalities. J Assist Reprod Genet 41, 2877–2929 (2024). https://doi.org/10.1007/s10815-024-03274-8
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DOI: https://doi.org/10.1007/s10815-024-03274-8