The role of theca cells in ovarian follicle atresia in cattle

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Over the last 50 years, there has been a major decline in fertility in dairy cattle worldwide, such that 70% of the average North American dairy herd is subfertile. This represents a major loss of income and the environmental cost of maintaining extra cattle for breeding is becoming inacceptable. The long-term goal of my NSERC research program is to understand the mechanisms of infertility in cattle, in order to propose solutions for the Canadian dairy industry.***Infertility in females can be caused by problems at the level of the ovary, the uterus or the pituitary gland. My research focuses on the ovary. In the ovary, the egg (oocyte) is contained within a fluid-filled structure called the follicle. In species such as cattle and humans, several follicles start to grow synchronously at the beginning of an estrous cycle, but only one grows large enough to release an egg at ovulation; the remainder regress. The reasons why follicles regress are not clear, but likely involves a complex series of hormonal interactions within the follicle.***The follicle contains three major cell types, the oocyte, granulosa cells and theca cells. Over the last 10 years, there has been a lot of research into the hormonal interactions between the oocyte and granulosa cells. This is logical, as when a follicle starts to regress, it is the granulosa cells that are most affected; they cease secreting important hormones and they show signs of cell death. However, my lab has recently provided novel evidence that the other cell type, the theca cell, may play a role in sensitizing granulosa cells to death signals. We identified an atypical member of the Fibroblast Growth Factor family of hormones, FGF18, that causes cell death when applied to granulosa cells in culture, and which is secreted in higher concentrations from theca cells of regressing compared to healthy follicles. In this next phase of my programme, we will (a) determine the factors that increase FGF18 secretion from theca cells, (b) determine the mechanism of action of FGF18 on granulosa cells, and (c) search for other factors secreted by theca cells that may determine the fate of the ovarian follicle.***Identifying factors secreted by theca cells that cause granulosa cell death will provide treatment options to prevent follicle regression. This would be applicable to cattle, and potentially to other species that undergo the same profile of follicle growth, including sheep, horses and endangered species.**