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Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch

1
Institute of Anatomy, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, Germany
2
Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, Lower Saxony, Germany
3
Clinic for Cattle, University of Veterinary Medicine Hannover, Foundation, 30173 Hannover, Lower Saxony, Germany
4
Platform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research, 37077 Göttingen, Lower Saxony, Germany
5
Department of Pathology, University of California San Francisco, San Francisco, CA 94143-0794, USA
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Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, San Francisco, CA 94143-0794, USA
7
Institute of Human Genetics, University of California San Francisco, San Francisco, CA 94143-0794, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 676; https://doi.org/10.3390/cells9030676
Received: 11 February 2020 / Revised: 4 March 2020 / Accepted: 5 March 2020 / Published: 10 March 2020
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., Dmrtb1, Sohlh1). In contrast, SC-specific genes implicated in SC maturation and proliferation were mostly upregulated (e.g., Amh, Fshr). 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. View Full-Text
Keywords: Cx43; impaired spermatogenesis; mitosis-meiosis switch; Sertoli cell maturation; NGS Cx43; impaired spermatogenesis; mitosis-meiosis switch; Sertoli cell maturation; NGS
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MDPI and ACS Style

Hilbold, E.; Distl, O.; Hoedemaker, M.; Wilkening, S.; Behr, R.; Rajkovic, A.; Langeheine, M.; Rode, K.; Jung, K.; Metzger, J.; Brehm, R.H.J. Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch. Cells 2020, 9, 676. https://doi.org/10.3390/cells9030676

AMA Style

Hilbold E, Distl O, Hoedemaker M, Wilkening S, Behr R, Rajkovic A, Langeheine M, Rode K, Jung K, Metzger J, Brehm RHJ. Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch. Cells. 2020; 9(3):676. https://doi.org/10.3390/cells9030676

Chicago/Turabian Style

Hilbold, Erika, Ottmar Distl, Martina Hoedemaker, Sandra Wilkening, Rüdiger Behr, Aleksandar Rajkovic, Marion Langeheine, Kristina Rode, Klaus Jung, Julia Metzger, and Ralph H.J. Brehm 2020. "Loss of Cx43 in Murine Sertoli Cells Leads to Altered Prepubertal Sertoli Cell Maturation and Impairment of the Mitosis-Meiosis Switch" Cells 9, no. 3: 676. https://doi.org/10.3390/cells9030676

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