The control of oocyte survival by intrinsic and extrinsic factors.

CAPSULE: Mechanisms that control the survival of oocytes and, by extension, the duration of ovarian function have been identified. However, it is still not clear whether oocyte "quality" is related to survival, nor is the role of the granulosa cells of follicles in follicle survival entirely understood. Here, we consider oocyte-intrinsic and oocyte-extrinsic mechanisms of oocyte loss and argue that developing a better understanding of such physiological events is needed to protect fertility, fecundity, and ovarian function in women.The duration that ovaries function is, as is intuitive, controlled by the number of remaining oocytes within follicles. Once the number of follicles drops beneath a threshold number, ovarian function ceases. Thus, understanding mechanisms that control oocyte survival is paramount as we consider strategies to protect or prolong ovarian function in women. It is often assumed that physiological oocyte survival is entirely controlled by "oocyte- intrinsic" factors, such as poor genetic quality or accumulated damage to the oocyte itself. Oocytes that have poor genetic quality due to development or accumulated damage would then die sooner than those of higher "quality." Indeed, new data suggest that oocyte-intrinsic genetic quality as determined by the ability to repair double-stranded DNA breaks is a significant contributor to oocyte survival and the duration of ovarian function. However, the nature of the follicle, where the oocyte and surrounding granulosa cells exist in intimate contact and rely upon each other for survival signals and metabolic function, makes it unlikely that oocyte-intrinsic factors entirely control oocyte survival. We and others are assessing the role of adjacent somatic (granulosa) cells in follicle survival, determining the relative importance of "oocyte-extrinsic" factors.