MECHANISMS, REGULATION AND MANIPULATIONS OF FOLLICULAR ATRESIA

In ovaries of mammals, an intense loss of germinal cells occurs by fol licular atresia throughout the life. In atretic antral follicles, gran ulosa cells stop proliferating and become apoptotic, Main effecters of apoptosis are caspases which are activated by two ways in granulosa c ells, the one involving Fas/TNF-alpha receptor, the other involving fa ctors of the bel-2 family. Atresia is triggered when some essential fa ctors supporting follicular development are lacking. Particularly, ter minal follicular development is strictly dependent upon gonadotropin ( FSH, then LH in the final preovulatory stage) supply, but factors acti ng in a paracrine way (growth factors, cytokines, steroids, constituan ts of extracellular matrix) play also important roles in amplifying go nadotropin action in follicular cells. Some pathological situations su ch as premature ovarian failure would result from accelerated follicul ar atresia, tiggered by interactions between follicular cells and cell s of the immune system. Current methods to control atresia consist in administrating exogenous gonadotropins, or indirectly increasing endog enous gonadotropins, or increasing follicular cell responsiveness to g onadotropins.