Interpretive Summary: Effect of bone morphogenetic protein 4, gremlin, and connective tissue growth factor on estradiol and progesterone production by bovine granulosa cells 

By: Dr. Emily Taylor

It has been well documented that Bone morphogenic proteins (BMPs) participate in the paracrine regulation of granulosa cell function in multiple species. However, it is unknown if responses to BMPs change with follicular size or interacts with connective tissue growth factor (CTGF) or BMP antagonists (e.g., gremlin) to directly affect granulosa cell function in cattle. Therefore, the current study objective was to determine the effects of BMP4 on proliferation and steroidogenesis of granulosa cells and its interaction with gremlin or CTGF. These studies were conducted using bovine granulosa cell cultures. 

BMP4 inhibited progesterone and estradiol production induced by follicle stimulating hormone (FSH) and insulin-like growth factor -1 (IGF1) in small- and large-follicle granulosa cells. The inhibitory effect of BMP4 on estradiol production was much more pronounced in large-follicle granulosa cells. The BMP4-induced proliferation of granulosa cells from large follicles was decreased by gremlin. In addition, gremlin also decreased estradiol production by granulosa cells from both small and large follicles. In the absence of BMP4, CTGF inhibited estradiol and progesterone production and blocked the stimulatory effect of BMP4 on the proliferation of large-follicle granulosa cells. 

In conclusion, BMP4, gremlin, and CTGF decreased hormone-induced steroidogenesis in granulosa cells, and therefore should be considered essential regulators of follicular function in cattle. Authors suggest further research is needed to identify comprehensive dose-response interactions among these and other ovarian factors. A better understanding of their role and molecular mechanisms that regulate granulosa cell function will be a useful tool needed to determine how these signals impact follicular development and their progression into ovarian cysts.

This article is now available in the Journal of Animal Science.