Control of oocyte growth and maturation by follicular cells and molecules present in follicular fluid. A review.

The aim of this review is to summarize the interactions between the oocyte and its surrounding granulosa cells which are involved in the control of oocyte growth or apoptosis as well as those playing a key role in the ability of the oocyte to undergo nuclear (resumption as meiosis to reach the MII stage) or cytoplasmic maturation (ability to fertilize and develop to the blastocyst stage). The respective roles of the oocyte and of the granulosa cells in controlling the initiation of growth are poorly understood. During the preantral follicular stage when most oocyte growth is achieved, a local regulation appears to be in operation involving growth factors such as fibroblast growth factor (FGF) or epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha), together with two proteins (c-kit present on the oocyte's membrane and its ligand KL produced by granulosa cells). In-situ techniques used to detect apoptosis demonstrate apoptotic oocytes in the reserves of primordial follicles but seldom within preantral follicles (because it is too fast?). Proteins involved in cell death (bax) or cell survival (bcl2) are present in oocytes as well as compounds (TNF alpha, Fas) involved in the initiation of apoptosis. However, the molecular and cellular mechanisms triggering oocyte apoptosis are not fully clarified. Three approaches have been used to identify compounds which are relevant to the oocyte's nuclear or cytoplasmic maturation. a) Correlation between amounts of specific compounds in follicular fluid or within follicle cells and the oocyte's ability to mature. b) Analysis of the consequences of pharmacological disruption of mechanisms such as steroidogenesis on oocyte maturation. c) Analysis of the consequences of addition of graded amounts of specific compounds on oocyte maturation in defined media. Factors playing a key role in stimulating nuclear maturation appear to be epidermal growth factor (EGF) and the inhibin (cattle)/activin (rodents) family, while testosterone has an inhibitory effect. Cytoplasmic maturation of the oocyte appears to be stimulated by oestradiol, EGF and inhibin.