L'atrésie folliculaire, un gaspillage programmé.

Abstract

Une gigantesque perte de cellules germinales se produit dans les ovaires des mammiferes, tout au long de leur vie, par atresie folliculaire, c' est-a-dire degenerescence du follicule empechant l' expulsion de l' ovule. Quatre-vingt-dix-neuf pour cent des follicules qui entrent en croissance degenerent. L' etape determinant la survie est l' expression de recepteurs de la LH par les cellules de la granulosa. Des facteurs de croissance tels que IGF-I amplifient l' action des gonadotrophines. Si l' environnement endocrine ou paracrine est insuffisant, l' apoptose se declenche dans les cellules de la granulosa : activation de Fas et du recepteur du TNF<alpha>, desequilibre en faveur des facteurs pro-apoptotiques (Bax) au detriment des facteurs anti-apoptotiques (Bcl-2), activation de p53 et des caspases. Le choix du follicule qui va se developper alors que les autres subissent l' atresie semble stochastique mais le processus n' est pas d' emblee irreversible.

In ovaries of mammals, an intense loss of germinal cells occurs by follicular atresia throughout the life. In granulosa cells of antral follicles, early stages of atresia are characterized by an increase in apoptotic rate, a decrease in proliferation rate and the loss of P450 aromatase expression. In addition, an increase in insulin-like growth factor binding proteins (particularly IGFBP-2) expression by follicular cells is observed. These early changes might be, at least for some of them, the cause of later changes such as the loss of gonadotropin responsiveness of follicular cells. A follicle dies when some essential factors supporting its development are lacking. In small preantral follicles, growth factors and cytokines such as Steel factor are limitant for follicular growth. Terminal follicular development is strictly dependent upon gonadotropin (FSH, then LH in the final preovulatory stage) supply, but growth factors such as IGF-I play also important roles in amplifying gonadotropin action in follicular cells. When the endocrine and/or paracrine environment is inadequate for the antral follicle, apoptosis is triggered in granulosa cells. Main effectors of apoptosis are caspases which are activated by two ways in granulosa cells, the one involving Fas/TNF-alpha receptor, the other involving factors of the Bcl-2 family. Transcriptional events, such as increase in p53, Bax, caspases and decrease in Bcl-xL expression, enhance these processes in granulosa cells. Why, when two follicles of the same size are submitted to the same endocrine environment, one will develop while the other will become atretic, is an essential question to answer. Two hypotheses are proposed, the first deterministic, the second stochastic. It is suggested that some of the primordial follicles which begin to grow are predetermined to degenerate in the preantral stage. By contrast, the choice of the ovulatory follicle (and atresia of the others) occurs partly at random at each ovarian cycle. It results in selection of the 'best' follicle at a given time and in a given endocrine environment. Determination of ovulation rate and, consequently, success of reproduction are tightly related to the programmed wastage of follicles which is atresia. [References: 44]