Reactive oxygen and nitrogen species: multifaceted regulators of ovarian activity†.

Reactive oxygen and nitrogen species are essential components of diverse intracellular signaling pathways. In addition to their involvement in apoptosis, reactive oxygen and nitrogen species are crucial in the regulation of multiple developmental and physiological processes. This review aims to summarize their role in the regulation of key ovarian stages: ovulation, maturation and postovulatory ageing of the oocyte, and the formation and regression of the corpus luteum. At the cellular level, a mild increase in reactive oxygen and nitrogen species is associated with the initiation of a number of regulatory mechanisms, which might be suppressed by increased activity of the antioxidant system. Moreover, a mild increase in reactive oxygen and nitrogen species has been linked to the control of mitochondrial biogenesis and abundance in response to increased cellular energy demands. Thus, reactive oxygen and nitrogen species should also be perceived in terms of their positive role in cellular signaling. On the other hand, an uncontrolled increase in reactive oxygen species production or strong down-regulation of the antioxidant system results in oxidative stress and damage of cellular components associated with ovarian pathologies and ageing. Similarly, the disturbance of signaling functions of reactive nitrogen species caused by dysregulation of nitric oxide production by nitric oxide synthases in ovarian tissues interferes with the proper regulation of physiological processes in the ovary.