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Submitted on January 13, 2005
Accepted on April 1, 2005
Laboratoire de Physiologie et Physiopathologie, CNRS-UMR 7079, Université Paris VI, Paris, France; Laboratoire de Pathologie Hormonale Moléculaire, INSERM U-135, Hopital Debrousse, Lyon, France
* To whom correspondence should be addressed. E-mail: solange.magre{at}snv.jussieu.fr.
While it has been suggested that in mammals, the loss of female germ cells may induce the masculinization of the ovarian compartment, there has as yet no conclusive demonstration. To directly address that question, the present study has been designed to determine the fate of follicular cells after oocyte loss. Using 
-irradiation to selectively deplete oocytes in non growing follicles in female rats, we show that follicular cells in oocyte-depleted follicles (ODF) survive, proliferate and subsequently acquire morphological characteristics of Sertoli cells: elongated cytoplasm, basal location of the nucleus and specific Sertoli cell junctions, the ‘ectoplasmic specializations’. These ‘Sertoli-like cells’ express, however, the female-specific marker FOXL2 and not the male sex specific marker SOX-9, underlying the maintenance of molecular characteristics of granulosa cells. Before transdifferentiating into Sertoli-like cells, follicular cells of ODF initiate the expression of AMH and inhibin 
subunit that are typically synthesized by granulosa cells from the onset of follicular growth. Experimental modifications of the endocrine balance of the irradiated females show that there is a close relationship between plasma FSH levels and the occurrence of Sertoli-like cells. In addition to providing experimental evidence for the crucial role of the oocyte in granulosa cell phenotype maintenance, these results emphasize that the transdifferentiation of granulosa cells into Sertoli cells occurs in a multistep fashion, requiring the maturation of granulosa cells and depending on the endocrine milieu.
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