Consequences of RAS and MAPK activation in the ovary: the good, the bad and the ugly.

This review summarizes studies providing evidence (1) that endogenous RAS activation regulates important physiological events during ovulation and luteinization (2) that expression of the mutant, active KRAS(G12D) in granulosa cells in vivo causes abnormal follicle growth arrest leading to premature ovarian failure and (3) that KRAS(G12D) expression in ovarian surface epithelial (OSE) cells renders them susceptible to the pathological outcome of transformation and tumor formation. These diverse effects of RAS highlight how critical its activation is linked to cell- and stage-specific events in the ovary that control normal processes and that can also lead to altered granulosa cell and OSE cell fates.