Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia

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Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia. / Han, Fei; Jiang, Xiao; Li, Zhi ming; Zhuang, Xuan; Zhang, Xi; Ouyang, Wei ming; Liu, Wen bin; Mao, Cheng yi; Chen, Qing; Huang, Chuan shu; Gao, Fei; Cui, Zhi hong; Ao, Lin; Li, Yan feng; Cao, Jia; Liu, Jin yi.

I: Molecular Therapy - Nucleic Acids, Bind 19, 2020, s. 72-83.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Han, F, Jiang, X, Li, ZM, Zhuang, X, Zhang, X, Ouyang, WM, Liu, WB, Mao, CY, Chen, Q, Huang, CS, Gao, F, Cui, ZH, Ao, L, Li, YF, Cao, J & Liu, JY 2020, 'Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia', Molecular Therapy - Nucleic Acids, bind 19, s. 72-83. https://doi.org/10.1016/j.omtn.2019.10.038

APA

Han, F., Jiang, X., Li, Z. M., Zhuang, X., Zhang, X., Ouyang, W. M., Liu, W. B., Mao, C. Y., Chen, Q., Huang, C. S., Gao, F., Cui, Z. H., Ao, L., Li, Y. F., Cao, J., & Liu, J. Y. (2020). Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia. Molecular Therapy - Nucleic Acids, 19, 72-83. https://doi.org/10.1016/j.omtn.2019.10.038

Vancouver

Han F, Jiang X, Li ZM, Zhuang X, Zhang X, Ouyang WM o.a. Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia. Molecular Therapy - Nucleic Acids. 2020;19:72-83. https://doi.org/10.1016/j.omtn.2019.10.038

Author

Han, Fei ; Jiang, Xiao ; Li, Zhi ming ; Zhuang, Xuan ; Zhang, Xi ; Ouyang, Wei ming ; Liu, Wen bin ; Mao, Cheng yi ; Chen, Qing ; Huang, Chuan shu ; Gao, Fei ; Cui, Zhi hong ; Ao, Lin ; Li, Yan feng ; Cao, Jia ; Liu, Jin yi. / Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia. I: Molecular Therapy - Nucleic Acids. 2020 ; Bind 19. s. 72-83.

Bibtex

@article{cef0ab89604542c0aa207f5a17717e2d,
title = "Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia",
abstract = "Non-obstructive azoospermia (NOA) is the most severe form of male infertility. However, the etiology of NOA is largely unknown, resulting in a lack of clinical treatments. Here, we performed a comparative genome-wide profiling of DNA methylation and identified SOX30 as the most notably hyper-methylated gene at promoter in testicular tissues from NOA patients. This hyper-methylation at promoter of SOX30 directly causes its silencing of expression in NOA. The reduced levels of SOX30 expression are correlated with severity of NOA disease. Deletion of Sox30 in mice uniquely impairs testis development and spermatogenesis with complete absence of spermatozoa in testes leading to male infertility, but does not influence ovary development and female fertility. The pathology and testicular size of Sox30 null mice highly simulate those of NOA patients. Re-expression of Sox30 in Sox30 null mice at adult age reverses the pathological damage of testis and restores the spermatogenesis. The re-presented spermatozoa after re-expression of Sox30 in Sox30 null mice have the ability to start a pregnancy. Moreover, the male offspring of Sox30 re-expression Sox30 null mice still can father children, and these male offspring and their children can live normally more than 1 year without significant difference of physical appearance compared with wild-type mice. In summary, methylated inactivation of SOX30 uniquely impairs spermatogenesis, probably causing NOA disease, and re-expression of SOX30 can successfully restore the spermatogenesis and actual fertility. This study advances our understanding of the pathogenesis of NOA, offering a promising therapy target for NOA disease.",
keywords = "male infertility, methylation, non-obstructive azoospermia, spermatogenesis, therapy target",
author = "Fei Han and Xiao Jiang and Li, {Zhi ming} and Xuan Zhuang and Xi Zhang and Ouyang, {Wei ming} and Liu, {Wen bin} and Mao, {Cheng yi} and Qing Chen and Huang, {Chuan shu} and Fei Gao and Cui, {Zhi hong} and Lin Ao and Li, {Yan feng} and Jia Cao and Liu, {Jin yi}",
year = "2020",
doi = "10.1016/j.omtn.2019.10.038",
language = "English",
volume = "19",
pages = "72--83",
journal = "Molecular Therapy - Nucleic Acids",
issn = "2162-2531",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Epigenetic Inactivation of SOX30 Is Associated with Male Infertility and Offers a Therapy Target for Non-obstructive Azoospermia

AU - Han, Fei

AU - Jiang, Xiao

AU - Li, Zhi ming

AU - Zhuang, Xuan

AU - Zhang, Xi

AU - Ouyang, Wei ming

AU - Liu, Wen bin

AU - Mao, Cheng yi

AU - Chen, Qing

AU - Huang, Chuan shu

AU - Gao, Fei

AU - Cui, Zhi hong

AU - Ao, Lin

AU - Li, Yan feng

AU - Cao, Jia

AU - Liu, Jin yi

PY - 2020

Y1 - 2020

N2 - Non-obstructive azoospermia (NOA) is the most severe form of male infertility. However, the etiology of NOA is largely unknown, resulting in a lack of clinical treatments. Here, we performed a comparative genome-wide profiling of DNA methylation and identified SOX30 as the most notably hyper-methylated gene at promoter in testicular tissues from NOA patients. This hyper-methylation at promoter of SOX30 directly causes its silencing of expression in NOA. The reduced levels of SOX30 expression are correlated with severity of NOA disease. Deletion of Sox30 in mice uniquely impairs testis development and spermatogenesis with complete absence of spermatozoa in testes leading to male infertility, but does not influence ovary development and female fertility. The pathology and testicular size of Sox30 null mice highly simulate those of NOA patients. Re-expression of Sox30 in Sox30 null mice at adult age reverses the pathological damage of testis and restores the spermatogenesis. The re-presented spermatozoa after re-expression of Sox30 in Sox30 null mice have the ability to start a pregnancy. Moreover, the male offspring of Sox30 re-expression Sox30 null mice still can father children, and these male offspring and their children can live normally more than 1 year without significant difference of physical appearance compared with wild-type mice. In summary, methylated inactivation of SOX30 uniquely impairs spermatogenesis, probably causing NOA disease, and re-expression of SOX30 can successfully restore the spermatogenesis and actual fertility. This study advances our understanding of the pathogenesis of NOA, offering a promising therapy target for NOA disease.

AB - Non-obstructive azoospermia (NOA) is the most severe form of male infertility. However, the etiology of NOA is largely unknown, resulting in a lack of clinical treatments. Here, we performed a comparative genome-wide profiling of DNA methylation and identified SOX30 as the most notably hyper-methylated gene at promoter in testicular tissues from NOA patients. This hyper-methylation at promoter of SOX30 directly causes its silencing of expression in NOA. The reduced levels of SOX30 expression are correlated with severity of NOA disease. Deletion of Sox30 in mice uniquely impairs testis development and spermatogenesis with complete absence of spermatozoa in testes leading to male infertility, but does not influence ovary development and female fertility. The pathology and testicular size of Sox30 null mice highly simulate those of NOA patients. Re-expression of Sox30 in Sox30 null mice at adult age reverses the pathological damage of testis and restores the spermatogenesis. The re-presented spermatozoa after re-expression of Sox30 in Sox30 null mice have the ability to start a pregnancy. Moreover, the male offspring of Sox30 re-expression Sox30 null mice still can father children, and these male offspring and their children can live normally more than 1 year without significant difference of physical appearance compared with wild-type mice. In summary, methylated inactivation of SOX30 uniquely impairs spermatogenesis, probably causing NOA disease, and re-expression of SOX30 can successfully restore the spermatogenesis and actual fertility. This study advances our understanding of the pathogenesis of NOA, offering a promising therapy target for NOA disease.

KW - male infertility

KW - methylation

KW - non-obstructive azoospermia

KW - spermatogenesis

KW - therapy target

U2 - 10.1016/j.omtn.2019.10.038

DO - 10.1016/j.omtn.2019.10.038

M3 - Journal article

C2 - 31835093

AN - SCOPUS:85076053801

VL - 19

SP - 72

EP - 83

JO - Molecular Therapy - Nucleic Acids

JF - Molecular Therapy - Nucleic Acids

SN - 2162-2531

ER -

ID: 234208617