Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis
HnRNPK is a heterogeneous nuclear ribonucleoprotein (hnRNP) that has been firmly implicated in transcriptional and post-transcriptional regulation. However, the molecular mechanisms by which hnRNPK orchestrates transcriptional or post-transcriptional regulation are not well understood due to early e...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/8/1277 |
| _version_ | 1827621364236812288 |
|---|---|
| author | Haixia Xu Jiahua Guo Wei Wu Qiu Han Yueru Huang Yaling Wang Cencen Li Xiaofang Cheng Pengpeng Zhang Yongjie Xu |
| author_facet | Haixia Xu Jiahua Guo Wei Wu Qiu Han Yueru Huang Yaling Wang Cencen Li Xiaofang Cheng Pengpeng Zhang Yongjie Xu |
| author_sort | Haixia Xu |
| collection | DOAJ |
| description | HnRNPK is a heterogeneous nuclear ribonucleoprotein (hnRNP) that has been firmly implicated in transcriptional and post-transcriptional regulation. However, the molecular mechanisms by which hnRNPK orchestrates transcriptional or post-transcriptional regulation are not well understood due to early embryonic lethality in homozygous knockout mice, especially in a tissue-specific context. Strikingly, in this study, we demonstrated that hnRNPK is strongly expressed in the mouse testis and mainly localizes to the nucleus in spermatogonia, spermatocytes, and round spermatids, suggesting an important role for hnRNPK in spermatogenesis. Using a male germ cell-specific hnRNPK-depleted mouse model, we found that it is critical for testicular development and male fertility. The initiation of meiosis of following spermatogenesis was not affected in <i>Hnrnpk</i> cKO mice, while most germ cells were arrested at the pachytene stage of the meiosis and no mature sperm were detected in epididymides. The further RNA-seq analysis of <i>Hnrnpk</i> cKO mice testis revealed that the deletion of hnRNPK disturbed the expression of genes involved in male reproductive development, among which the meiosis genes were significantly affected, and <i>Hnrnpk</i> cKO spermatocytes failed to complete the meiotic prophase. Together, these results identify hnRNPK as an essential regulator of spermatogenesis and male fertility. |
| first_indexed | 2024-03-09T11:02:33Z |
| format | Article |
| id | doaj.art-cc79da57a0d440ec81e362a6851444c5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T11:02:33Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-cc79da57a0d440ec81e362a6851444c52023-12-01T01:13:11ZengMDPI AGCells2073-44092022-04-01118127710.3390/cells11081277Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting SpermatogenesisHaixia Xu0Jiahua Guo1Wei Wu2Qiu Han3Yueru Huang4Yaling Wang5Cencen Li6Xiaofang Cheng7Pengpeng Zhang8Yongjie Xu9College of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaCollege of Life Science, Xinyang Normal University, Xinyang 464000, ChinaHnRNPK is a heterogeneous nuclear ribonucleoprotein (hnRNP) that has been firmly implicated in transcriptional and post-transcriptional regulation. However, the molecular mechanisms by which hnRNPK orchestrates transcriptional or post-transcriptional regulation are not well understood due to early embryonic lethality in homozygous knockout mice, especially in a tissue-specific context. Strikingly, in this study, we demonstrated that hnRNPK is strongly expressed in the mouse testis and mainly localizes to the nucleus in spermatogonia, spermatocytes, and round spermatids, suggesting an important role for hnRNPK in spermatogenesis. Using a male germ cell-specific hnRNPK-depleted mouse model, we found that it is critical for testicular development and male fertility. The initiation of meiosis of following spermatogenesis was not affected in <i>Hnrnpk</i> cKO mice, while most germ cells were arrested at the pachytene stage of the meiosis and no mature sperm were detected in epididymides. The further RNA-seq analysis of <i>Hnrnpk</i> cKO mice testis revealed that the deletion of hnRNPK disturbed the expression of genes involved in male reproductive development, among which the meiosis genes were significantly affected, and <i>Hnrnpk</i> cKO spermatocytes failed to complete the meiotic prophase. Together, these results identify hnRNPK as an essential regulator of spermatogenesis and male fertility.https://www.mdpi.com/2073-4409/11/8/1277hnRNPKmeiosistranscriptional regulationspermatocytesspermatogenesis |
| spellingShingle | Haixia Xu Jiahua Guo Wei Wu Qiu Han Yueru Huang Yaling Wang Cencen Li Xiaofang Cheng Pengpeng Zhang Yongjie Xu Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis Cells hnRNPK meiosis transcriptional regulation spermatocytes spermatogenesis |
| title | Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis |
| title_full | Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis |
| title_fullStr | Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis |
| title_full_unstemmed | Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis |
| title_short | Deletion of <i>Hn</i><i>rnpk</i> Gene Causes Infertility in Male Mice by Disrupting Spermatogenesis |
| title_sort | deletion of i hn i i rnpk i gene causes infertility in male mice by disrupting spermatogenesis |
| topic | hnRNPK meiosis transcriptional regulation spermatocytes spermatogenesis |
| url | https://www.mdpi.com/2073-4409/11/8/1277 |
| work_keys_str_mv | AT haixiaxu deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT jiahuaguo deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT weiwu deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT qiuhan deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT yueruhuang deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT yalingwang deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT cencenli deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT xiaofangcheng deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT pengpengzhang deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis AT yongjiexu deletionofihniirnpkigenecausesinfertilityinmalemicebydisruptingspermatogenesis |