Programmed Cell Death in the Ovary: Insights and Future Prospects Using Genetic Technologies

Programmed cell death (PCD) plays a prominent role in development of the fetal ovaries and in the postnatal ovarian cycle. As is the case with other major organ systems, an evolutionarily conserved framework of genes and signaling pathways has been implicated in determining whether or not ovarian germ cells and somatic cells will die in response to either developmental cues or pathological insults. However, the identification of increasing numbers of potential ovarian cell death regulatory factors over the past several years has underscored the need for studies to now separate correlation (e.g. endogenous gene expression) from function (e.g. requirement of the gene product for the execution of PCD). In this regard, genetic technologies have recently been used to examine the functional significance of specific proteins and signaling molecules to the regulation of PCD in the female gonad in vivo. In addition to the more classic approaches, such as the use of genetic null and transgenic mice, methods that achieve cell lineage-selective and/or developmentally timed gene targeting are on the horizon for use by reproductive biologists to more accurately dissect the mechanisms by which PCD is controlled in the ovary. This minireview will highlight some of the advances that have already been made using gene knockout and transgenic mice, as well as provide an overview of the current and future status of cell lineage-selective gene disruption, in the context of PCD and ovarian function.