Involvement of Bone Morphogenetic Proteins (BMP) in the Regulation of Ovarian Function

Primordial germ cells migrate to the fetal gonads and proliferate during gestation to generate a fixed complement of primordial follicles, the so-called ovarian reserve. Primordial follicles comprise an oocyte arrested at the diplotene stage of meiosis, surrounded by a layer of pregranulosa cells. Activation of primordial follicles to grow beyond this arrested stage is of particular interest because, once activated, they are subjected to regulatory mechanisms involved in growth, selection, maturation, and ultimately, ovulation or atresia. The vast majority of follicles succumb to atresia and are permanently lost from the quiescent or growing pool of follicles. The bone morphogenetic proteins (BMPs), together with other intraovarian growth factors, are intimately involved in regulation of follicle recruitment, dominant follicle selection, ovulation, and atresia. Activation of primordial follicles appears to be a continuous process, and the number of small antral follicles at the beginning of the menstrual cycle provides an indirect indication of ovarian reserve. Continued antral follicle development during the follicular phase of the menstrual cycle is driven by follicle stimulating hormone (FSH) and luteinizing hormone (LH) in conjunction with many intraovarian growth factors and inhibitors interrelated in a complex web of regulatory balance. The BMP signaling system has a major intraovarian role in many species, including the human, in the generation of transcription factors that influence proliferation, steroidogenesis, cell differentiation, and maturation prior to ovulation, as well as formation of corpora lutea after ovulation. At the anterior pituitary level, BMPs also contribute to the regulation of gonadotrophin production.