Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells
Abstract Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10–15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human tes...
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| Format: | Article |
| Language: | English |
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Wiley
2023-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202206852 |
| _version_ | 1827926275879075840 |
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| author | Yidong Chen Xixi Liu Li Zhang Feiyin Zhu Liying Yan Wenhao Tang Zhe Zhang Qiang Liu Hui Jiang Jie Qiao |
| author_facet | Yidong Chen Xixi Liu Li Zhang Feiyin Zhu Liying Yan Wenhao Tang Zhe Zhang Qiang Liu Hui Jiang Jie Qiao |
| author_sort | Yidong Chen |
| collection | DOAJ |
| description | Abstract Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10–15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human testicular single‐cell transcriptomes from 17 iNOA patients, which are classified into four classes with different arrest periods and variable cell proportions based on the gene expression patterns and pathological features. Genes related to the cell cycle, energy production, and gamete generation show obvious abnormalities in iNOA germ cells. This work identifies several candidate causal genes for iNOA, including CD164, LELP1, and TEX38, which are significantly downregulated in iNOA germ cells. Notably, CD164 knockdown promotes apoptosis in spermatogonia. Cellular communications between spermatogonial stem cells and Sertoli cells are disturbed in iNOA patients. Moreover, BOD1L2, C1orf194, and KRTCAP2 are found to indicate testicular spermatogenic capacity in a variety of testicular diseases, such as Y‐chromosome microdeletions and Klinefelter syndrome. In general, this study analyzes the pathogenesis of iNOA from the perspective of germ cell development, transcription factor (TF) regulatory networks, as well as germ cell and somatic cell interactions, which provides new ideas for clinical diagnosis. |
| first_indexed | 2024-03-13T05:36:48Z |
| format | Article |
| id | doaj.art-b15397eb2a6f4ca685efef777b53b039 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-13T05:36:48Z |
| publishDate | 2023-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-b15397eb2a6f4ca685efef777b53b0392023-06-14T07:18:56ZengWileyAdvanced Science2198-38442023-06-011017n/an/a10.1002/advs.202206852Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ CellsYidong Chen0Xixi Liu1Li Zhang2Feiyin Zhu3Liying Yan4Wenhao Tang5Zhe Zhang6Qiang Liu7Hui Jiang8Jie Qiao9Center for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaDepartment of Urology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaDepartment of Urology Peking University Third Hospital Beijing 100191 ChinaCenter for Reproductive Medicine Department of Obstetrics and Gynecology Peking University Third Hospital Beijing 100191 ChinaAbstract Nonobstructive azoospermia (NOA) is one of the most important causes of male infertility, accounting for 10–15% of infertile men worldwide. Among these, more than 70% of cases are idiopathic NOA (iNOA), whose pathogenesis and molecular basis remain unknown. This work profiles 3696 human testicular single‐cell transcriptomes from 17 iNOA patients, which are classified into four classes with different arrest periods and variable cell proportions based on the gene expression patterns and pathological features. Genes related to the cell cycle, energy production, and gamete generation show obvious abnormalities in iNOA germ cells. This work identifies several candidate causal genes for iNOA, including CD164, LELP1, and TEX38, which are significantly downregulated in iNOA germ cells. Notably, CD164 knockdown promotes apoptosis in spermatogonia. Cellular communications between spermatogonial stem cells and Sertoli cells are disturbed in iNOA patients. Moreover, BOD1L2, C1orf194, and KRTCAP2 are found to indicate testicular spermatogenic capacity in a variety of testicular diseases, such as Y‐chromosome microdeletions and Klinefelter syndrome. In general, this study analyzes the pathogenesis of iNOA from the perspective of germ cell development, transcription factor (TF) regulatory networks, as well as germ cell and somatic cell interactions, which provides new ideas for clinical diagnosis.https://doi.org/10.1002/advs.202206852clinical diagnosisgerm cellsmolecular characteristicsnonobstructive azoospermiapathogenesisspermatogenic capacity predictor |
| spellingShingle | Yidong Chen Xixi Liu Li Zhang Feiyin Zhu Liying Yan Wenhao Tang Zhe Zhang Qiang Liu Hui Jiang Jie Qiao Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells Advanced Science clinical diagnosis germ cells molecular characteristics nonobstructive azoospermia pathogenesis spermatogenic capacity predictor |
| title | Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells |
| title_full | Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells |
| title_fullStr | Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells |
| title_full_unstemmed | Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells |
| title_short | Deciphering the Molecular Characteristics of Human Idiopathic Nonobstructive Azoospermia from the Perspective of Germ Cells |
| title_sort | deciphering the molecular characteristics of human idiopathic nonobstructive azoospermia from the perspective of germ cells |
| topic | clinical diagnosis germ cells molecular characteristics nonobstructive azoospermia pathogenesis spermatogenic capacity predictor |
| url | https://doi.org/10.1002/advs.202206852 |
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