DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia

Ann Kristin Dicke; Adrian Pilatz; Margot J. Wyrwoll; Margus Punab; Christian Ruckert; Liina Nagirnaja; Kenneth I. Aston; Donald F. Conrad; Sara Di Persio; Nina Neuhaus; Daniela Fietz; Maris Laan; Birgit Stallmeyer; Frank Tüttelmann

doi:10.1038/s42003-023-04714-4

DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia

Ann Kristin Dicke, Adrian Pilatz, Margot J. Wyrwoll, Margus Punab, Christian Ruckert, Liina Nagirnaja, Kenneth I. Aston, Donald F. Conrad, Sara Di Persio, Nina Neuhaus, Daniela Fietz, Maris Laan, Birgit Stallmeyer, Frank Tüttelmann

Oregon National Primate Research Center

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Non-obstructive azoospermia, the absence of sperm in the ejaculate due to disturbed spermatogenesis, represents the most severe form of male infertility. De novo microdeletions of the Y-chromosomal AZFa region are one of few well-established genetic causes for NOA and are routinely analysed in the diagnostic workup of affected men. So far, it is unclear which of the three genes located in the AZFa chromosomal region is indispensible for germ cell maturation. Here we present four different likely pathogenic loss-of-function variants in the AZFa gene DDX3Y identified by analysing exome sequencing data of more than 1,600 infertile men. Three of the patients underwent testicular sperm extraction and revealed the typical AZFa testicular Sertoli cell-only phenotype. One of the variants was proven to be de novo. Consequently, DDX3Y represents the AZFa key spermatogenic factor and screening for variants in DDX3Y should be included in the diagnostic workflow.

Original language	English (US)
Article number	350
Journal	Communications Biology
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s42003-023-04714-4
State	Published - Dec 2023

ASJC Scopus subject areas

Medicine (miscellaneous)
General Biochemistry, Genetics and Molecular Biology
General Agricultural and Biological Sciences

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Dicke, A. K., Pilatz, A., Wyrwoll, M. J., Punab, M., Ruckert, C., Nagirnaja, L., Aston, K. I., Conrad, D. F., Di Persio, S., Neuhaus, N., Fietz, D., Laan, M., Stallmeyer, B., & Tüttelmann, F. (2023). DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia. Communications Biology, 6(1), Article 350. https://doi.org/10.1038/s42003-023-04714-4

Dicke, AK, Pilatz, A, Wyrwoll, MJ, Punab, M, Ruckert, C, Nagirnaja, L, Aston, KI, Conrad, DF, Di Persio, S, Neuhaus, N, Fietz, D, Laan, M, Stallmeyer, B & Tüttelmann, F 2023, 'DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia', Communications Biology, vol. 6, no. 1, 350. https://doi.org/10.1038/s42003-023-04714-4

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abstract = "Non-obstructive azoospermia, the absence of sperm in the ejaculate due to disturbed spermatogenesis, represents the most severe form of male infertility. De novo microdeletions of the Y-chromosomal AZFa region are one of few well-established genetic causes for NOA and are routinely analysed in the diagnostic workup of affected men. So far, it is unclear which of the three genes located in the AZFa chromosomal region is indispensible for germ cell maturation. Here we present four different likely pathogenic loss-of-function variants in the AZFa gene DDX3Y identified by analysing exome sequencing data of more than 1,600 infertile men. Three of the patients underwent testicular sperm extraction and revealed the typical AZFa testicular Sertoli cell-only phenotype. One of the variants was proven to be de novo. Consequently, DDX3Y represents the AZFa key spermatogenic factor and screening for variants in DDX3Y should be included in the diagnostic workflow.",

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AU - Pilatz, Adrian

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AU - Punab, Margus

AU - Ruckert, Christian

AU - Nagirnaja, Liina

AU - Aston, Kenneth I.

AU - Conrad, Donald F.

AU - Di Persio, Sara

AU - Neuhaus, Nina

AU - Fietz, Daniela

AU - Laan, Maris

AU - Stallmeyer, Birgit

AU - Tüttelmann, Frank

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AB - Non-obstructive azoospermia, the absence of sperm in the ejaculate due to disturbed spermatogenesis, represents the most severe form of male infertility. De novo microdeletions of the Y-chromosomal AZFa region are one of few well-established genetic causes for NOA and are routinely analysed in the diagnostic workup of affected men. So far, it is unclear which of the three genes located in the AZFa chromosomal region is indispensible for germ cell maturation. Here we present four different likely pathogenic loss-of-function variants in the AZFa gene DDX3Y identified by analysing exome sequencing data of more than 1,600 infertile men. Three of the patients underwent testicular sperm extraction and revealed the typical AZFa testicular Sertoli cell-only phenotype. One of the variants was proven to be de novo. Consequently, DDX3Y represents the AZFa key spermatogenic factor and screening for variants in DDX3Y should be included in the diagnostic workflow.

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DDX3Y is likely the key spermatogenic factor in the AZFa region that contributes to human non-obstructive azoospermia

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