Loss of tight junction integrity abolishes the epithelial phenotype: the case of Claudin11deficiency in testis. : Claudin11 and loss of the Sertoli cell epithelial phenotype

Séverine Mazaud-Guittot 1 Emmanuelle Meugnier 1 Sandra Pesenti 1 X. Wu 2 H Vidal 1 A Gow 2, 3, 4 Brigitte Le Magueresse-Battistoni 1, *
* Corresponding author
1 RMND - Régulations métaboliques, nutrition et diabètes
2 Center For Molecular Medicine and Genetics
3 Karman and Ann Adams Department of Pediatrics [Detroit, MI, USA]
4 Department of Neurology [Detroit, MI, USA]
Abstract : Tissue integrity relies on barriers formed between epithelial cells. In the testis, the barrier is formed at the initiation of puberty by a tight junction complex between adjacent Sertoli cells, thereby defining an adluminal compartment where meiosis and spermiogenesis occur. Claudin11 is an obligatory protein for tight junction formation and barrier integrity in the testis. It is expressed by Sertoli cells, and spermatogenesis does not proceed beyond meiosis in its absence, resulting in male sterility. Sertoli cell maturation – arrest of proliferation and expression of proteins to support germ cell development – is known to parallel tight junction assembly; however, the pathophysiology underlying the loss of tight junctions in the mature testis remains largely undefined. Herein, we use immunohistochemistry and microarrays in wild-type and Claudin11-/-testes from mice to demonstrate that adult Claudin11-/-Sertoli cells re-enter the cell cycle while maintaining expression of several differentiation markers. Dividing Sertoli cells lose polarity, detach from the basement membrane and are eliminated through the lumen together with apoptotic germ cells that they have phagocytosed. Thus, Claudin11-/-Sertoli cells exhibit a unique phenotype whereby loss of tight junction integrity results in loss of the epithelial phenotype but not the progression to a tumorigenic phenotype.
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Séverine Mazaud-Guittot, Emmanuelle Meugnier, Sandra Pesenti, X. Wu, H Vidal, et al.. Loss of tight junction integrity abolishes the epithelial phenotype: the case of Claudin11deficiency in testis. : Claudin11 and loss of the Sertoli cell epithelial phenotype. Biology of Reproduction, Society for the Study of Reproduction, 2010, 82 (1), pp.202-13. ⟨10.1095/biolreprod.109.078907⟩. ⟨inserm-01848512⟩

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