[The adult ovary is not in sleepiness: major role of forkhead proteins]

Abstract

The aim of this review is to underscore the major role of forkhead proteins in the adult ovary. Indeed, they revolutionize the idea of terminal differentiation of adult tissues with for example the in vivo reprogrammation of an adult organism on the one hand, and, on the other hand, the therapeutic possibilities of fertility preservation in women. In mammals, SRY, a transcription factor encoded by the Y chromosome, is responsible for the development of the undifferentiated gonads into testes. However, testis differentiation can occur in its absence. The studies of M. Treier demonstrate that FOXL2 is required to maintain the ovarian phenotype. Indeed, the absence of Foxl2 in an adult mouse ovary leads to an up regulation of testis-specific genes and a transformation of granulosa and theca cells into Sertoli-like and Leydig-like cells. The maintenance of the ovarian phenotype is an active process throughout life. Although multiple follicles are present in mammalian ovaries, most of them remain dormant. During reproductive life, some follicles are activated for development. There is an inefficient activation of dormant follicles within cryopreserved ovaries. An inhibition of the FOXO3a pathway in the mouse ovary leads to an enhancement of the activation of the dormant follicles. After transplantation, there are more preovulatory stage follicles and, after fertilization and embryo transfer, they lead to a healthy progeny. In human ovarian cortical fragments, the same inhibition and a xenotransplantation permit a development of more primordial follicles to the preovulatory stage. Thus, this treatment may be a hope to treat infertile women with cryopreserved ovaries or with a diminishing ovarian reserve.