Résumé

SY6-003

Misregulation of RSPO1 signaling induces various defects and cancers in mouse adult ovaries

MC. De Cian^a (Dr), E. Pauper^b (Dr), V. Vidal^b (Dr), I. Gillot^a (Dr), MC. Chaboissier*^c (Dr)

^a UNS, Nice, FRANCE ; ^b INSERM, Nice, FRANCE ; ^c CNRS, Nice, FRANCE

* chaboiss@unice.fr

R-spondin are secreted proteins involved in both embryonic development and homeostasis of adult organs in different species. R-spondin (RSPO) are activators of the canonical WNT signaling pathway and RSPO1 is a key regulator of ovarian differentiation ¹. The importance of RSPO1 in this process was highlighted by the linkage of mutations of the RSPO1 gene to female-to-male sex reversal (XX men), palmoplantar hyperkeratosis and a predisposition to squamous cell carcinoma in patients ². However the role of RSPO1 in the physiology of the adult ovary remained to be investigated. For this aim, we used a gain-of-function mouse model for Rspo1. The Rspo1 mutant mice are sterile and exhibit abnormal ovarian structures ranging from follicular like lesions to cancers. Our data show that the ectopic expression of Rspo1 in ovaries hampers ovarian cell differentiation and consequently ovarian function. This promotes the persistence of abnormal follicles that eventually become tumors. Altogether, these results suggest that RSPO1 has to be tightly regulated to allow proper ovarian development and maintenance of the healthy ovary.

1 Chassot, A. A. et al. Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet 17, 1264-1277 (2008).

2 Parma, P. et al. R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38, 1304-1309 (2006).

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