Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch
Male factor infertility is a problem in today’s society but many underlying causes are still unknown. The generation of a conditional Sertoli cell (SC)-specific connexin 43 (Cx43) knockout mouse line (SCCx43KO) has provided a translational model. Expression of the gap junction protein Cx43...
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MDPI AG
2020-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/676 |
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| author | Erika Hilbold Ottmar Distl Martina Hoedemaker Sandra Wilkening Rüdiger Behr Aleksandar Rajkovic Marion Langeheine Kristina Rode Klaus Jung Julia Metzger Ralph H. J. Brehm |
| author_facet | Erika Hilbold Ottmar Distl Martina Hoedemaker Sandra Wilkening Rüdiger Behr Aleksandar Rajkovic Marion Langeheine Kristina Rode Klaus Jung Julia Metzger Ralph H. J. Brehm |
| author_sort | Erika Hilbold |
| collection | DOAJ |
| description | Male factor infertility is a problem in today’s society but many underlying causes are still unknown. The generation of a conditional Sertoli cell (SC)-specific connexin 43 (Cx43) knockout mouse line (SCCx43KO) has provided a translational model. Expression of the gap junction protein Cx43 between adjacent SCs as well as between SCs and germ cells (GCs) is known to be essential for the initiation and maintenance of spermatogenesis in different species and men. Adult SCCx43KO males show altered spermatogenesis and are infertile. Thus, the present study aims to identify molecular mechanisms leading to testicular alterations in prepubertal SCCx43KO mice. Transcriptome analysis of 8-, 10- and 12-day-old mice was performed by next-generation sequencing (NGS). Additionally, candidate genes were examined by qRT-PCR and immunohistochemistry. NGS revealed many significantly differentially expressed genes in the SCCx43KO mice. For example, GC-specific genes were mostly downregulated and found to be involved in meiosis and spermatogonial differentiation (e.g., <i>Dmrtb1</i>, <i>Sohlh1</i>). In contrast, SC-specific genes implicated in SC maturation and proliferation were mostly upregulated (e.g., <i>Amh</i>, <i>Fshr</i>). In conclusion, Cx43 in SCs appears to be required for normal progression of the first wave of spermatogenesis, especially for the mitosis-meiosis switch, and also for the regulation of prepubertal SC maturation. |
| first_indexed | 2024-03-12T05:48:08Z |
| format | Article |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T05:48:08Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-02bb0f52021b4f5dac64466e394d1a2d2023-09-03T05:27:39ZengMDPI AGCells2073-44092020-03-019367610.3390/cells9030676cells9030676Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis SwitchErika Hilbold0Ottmar Distl1Martina Hoedemaker2Sandra Wilkening3Rüdiger Behr4Aleksandar Rajkovic5Marion Langeheine6Kristina Rode7Klaus Jung8Julia Metzger9Ralph H. J. Brehm10Institute of Anatomy, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, GermanyInstitute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Lower Saxony, GermanyClinic for Cattle, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, GermanyClinic for Cattle, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, GermanyPlatform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research, 37077 Göttingen, Lower Saxony, GermanyDepartment of Pathology, University of California San Francisco, San Francisco, CA 94143-0794, USAInstitute of Anatomy, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, GermanyInstitute of Anatomy, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, GermanyInstitute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Lower Saxony, GermanyInstitute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Lower Saxony, GermanyInstitute of Anatomy, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, GermanyMale factor infertility is a problem in today’s society but many underlying causes are still unknown. The generation of a conditional Sertoli cell (SC)-specific connexin 43 (Cx43) knockout mouse line (SCCx43KO) has provided a translational model. Expression of the gap junction protein Cx43 between adjacent SCs as well as between SCs and germ cells (GCs) is known to be essential for the initiation and maintenance of spermatogenesis in different species and men. Adult SCCx43KO males show altered spermatogenesis and are infertile. Thus, the present study aims to identify molecular mechanisms leading to testicular alterations in prepubertal SCCx43KO mice. Transcriptome analysis of 8-, 10- and 12-day-old mice was performed by next-generation sequencing (NGS). Additionally, candidate genes were examined by qRT-PCR and immunohistochemistry. NGS revealed many significantly differentially expressed genes in the SCCx43KO mice. For example, GC-specific genes were mostly downregulated and found to be involved in meiosis and spermatogonial differentiation (e.g., <i>Dmrtb1</i>, <i>Sohlh1</i>). In contrast, SC-specific genes implicated in SC maturation and proliferation were mostly upregulated (e.g., <i>Amh</i>, <i>Fshr</i>). In conclusion, Cx43 in SCs appears to be required for normal progression of the first wave of spermatogenesis, especially for the mitosis-meiosis switch, and also for the regulation of prepubertal SC maturation.https://www.mdpi.com/2073-4409/9/3/676cx43impaired spermatogenesismitosis-meiosis switchsertoli cell maturationngs |
| spellingShingle | Erika Hilbold Ottmar Distl Martina Hoedemaker Sandra Wilkening Rüdiger Behr Aleksandar Rajkovic Marion Langeheine Kristina Rode Klaus Jung Julia Metzger Ralph H. J. Brehm Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch Cells cx43 impaired spermatogenesis mitosis-meiosis switch sertoli cell maturation ngs |
| title | Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch |
| title_full | Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch |
| title_fullStr | Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch |
| title_full_unstemmed | Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch |
| title_short | Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch |
| title_sort | loss of cx43 in murine sertoli cells leads to altered prepubertal sertoli cell maturation and impairment of the mitosis meiosis switch |
| topic | cx43 impaired spermatogenesis mitosis-meiosis switch sertoli cell maturation ngs |
| url | https://www.mdpi.com/2073-4409/9/3/676 |
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