Nutritional and metabolic mechanisms in the ovary and their role in mediating the effects of diet on folliculogenesis: a perspective.

Folliculogenesis in ruminants is a nutritionally sensitive process, and short-term increases in nutrient flux can stimulate folliculogenesis in sheep and cattle. These short-term effects are probably mediated directly at the follicular level to modify gonadotrophin-induced follicle growth and development. The follicle appears to have a number of 'nutrient sensing' mechanism that may form the link between nutrient status and folliculogenesis. This review examines the evidence for the presence of pathways that may sense nutrient flux from within the follicle including the insulin signalling pathway, adenosine monophosphate-activated kinase (AMPK), the hexosamine pathway, peroxisome proliferator-activated receptors (PPARs) and leptin. The review then assesses the available evidence concerning their mechanisms in the follicle and speculates on how these 'nutrient sensing' pathways are integrated into the FSH signalling pathways to adjust gonadotrophin-stimulated follicular function. We conclude that there is good evidence to suggest that the follicle does contain more than one functional 'nutrient sensing' pathway that have intra-follicular effects on some FSH-mediated functions such as the synthesis of oestradiol, in granulosa cells. These pathways include insulin, AMPK, and leptin. There is also a good case for the integration of PPARs in the intra-follicular sensing of nutrient flux. However, there is little evidence at present to suggest the hexosamine biosynthetic pathway has functional significance in the follicle as a sensor of nutrient flux. Further study will be required to fully understand 'nutrient sensing' pathways in the follicle and their cross-talk with FSH signalling pathways.