Figure 2

The model ( left and above dotted line) shows the response of the pre-antral theca to inhibin B, which results in production of DHEA and PPARα in follicles from about 200 μ m. It is proposed that reduced levels of PPARα primarily account for both the decline in follicle number and the loss of oocyte quality that ultimately leads to errors of cell division and arrested development. The defects that occur in cytoplasmic organelles, especially mitochondria, are largely responsible for decline in follicle quality. These can be attributed to key changes in fat metabolism and transport and mitochondrial function that are directly caused by dysfunction of PPARα secondary to low DHEA. These same changes also lead to increased production of ceramide, apoptosis and hence accelerated decline in the size of the follicle pool. The area to the right of the dotted line indicates that in humans and those primates where the adrenal ZR produces an alternative source of DHEA, that age related loss of ZR cells accelerates the rate of aging in the late thirties age group.