Published online before print May 10, 2007

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(American Journal of Pathology. 2007;171:19-31.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.061171

A Sertoli Cell-Specific Knockout of Connexin43 Prevents Initiation of Spermatogenesis

Ralph Brehm^*, Martina Zeiler^*, Christina Rüttinger^*, Katja Herde^*, Mark Kibschull, Elke Winterhager, Klaus Willecke, Florian Guillou, Charlotte Lécureuil, Klaus Steger^¶, Lutz Konrad^||, Katharina Biermann^**, Klaus Failing and Martin Bergmann^*

From the Institute of Veterinary Anatomy, Histology, and Embryology,^* and the Unit for Biomathematics, Faculty of Veterinary Medicine, University of Giessen, Giessen, Germany; the Department of Urology and Pediatric Urology,^¶ University of Giessen, Giessen, Germany; the Institute of Anatomy, University Hospital Essen, Essen, Germany; the Institute for Genetics, the Division of Molecular Genetics, and the Institute of Pathology,^** University of Bonn, Bonn, Germany; the Department of Urology,|| University of Marburg, Marburg, Germany; and the Unité Mixte de Recherche 6175, Physiologie de la Reproduction, Institut National de la Recherche Agronomique-Centre National de la Recherche Scientifique, Université de Tours, Haras Nationaux, Nouzilly, France

The predominant testicular gap junctional protein connexin43 (cx43) is located between neighboring Sertoli cells (SCs) and between SCs and germ cells. It is assumed to be involved in testicular development, cell differentiation, initiation, and maintenance of spermatogenesis with alterations of its expression being correlated with various testicular disorders. Because total disruption of the cx43 gene leads to perinatal death, we generated a conditional cx43 knockout (KO) mouse using the Cre/loxP recombination system, which lacks the cx43 gene solely in SCs (SCCx43KO), to evaluate the SC-specific functions of cx43 on spermatogenesis in vivo. Adult SCCx43KO^–/– mice showed normal testis descent and development of the urogenital tract, but testis size and weight were drastically lower compared with heterozygous and wild-type littermates. Histological analysis and quantitation of mRNA expression of germ cell-specific marker genes revealed a significant reduction in the number of spermatogonia but increased SC numbers/tubule with only a few tubules left showing normal spermatogenesis. Thus, SC-specific deletion of cx43 mostly resulted in an arrest of spermatogenesis at the level of spermatogonia or SC-only syndrome and in intratubular SC clusters. Our data demonstrate for the first time that cx43 expression in SCs is an absolute requirement for normal testicular development and spermatogenesis.

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