Integral role of GDF‐9 and BMP‐15 in ovarian function

Abstract

SUMMARYThe oocyte plays an important role in regulating and promoting follicle growth, and thereby its own development, by the production of oocyte growth factors that predominantly act on supporting granulosa cells via paracrine signaling. Genetic studies in mice demonstrated critical roles of two key oocyte-derived growth factors belonging to the transforming growth factor-b (TGF-b) superfamily, growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15), in ovarian function. The identification of Bmp15 and Gdf9 gene mutations as the causal mechanism underlying the highly prolific or infertile nature of several sheep strains in a dosage-sensitive manner also highlighted the crucial role these two genes play in ovarian function. Similarly, large numbers of mutations in the GDF9 and BMP15 genes have been identified in women with premature ovarian failure and in mothers of dizygotic twins. The purpose of this article is to review the genetic studies of GDF-9 and BMP-15 mutations identified in women and sheep, as well as describing the various knockout and overexpressing mouse models, and to summarize the molecular and biological functions that underlie the crucial role of these two oocyte factors in female fertility.Mol. Reprod. Dev.78: 9-21, 2011. ß

Concentrations of bone morphogenetic protein-15 (BMP-15) and growth differentiation factor-9 (GDF-9) in follicular cysts, mono - and polyoocyte follicles in gilts

“…Amongst factors secreted by oocytes are BMP-15 and GDF-9. Current research focuses on the interrelation between an oocyte and follicular somatic cells [2][3][4][5]22]. The positive correlation between BMP-15 and GDF-9 demonstrated herein confi rms a synergistic activity of the aforementioned factors [1,6].…”

Notch signaling pathway in cumulus cells can be a novel marker to identify poor and normal responder IVF patients

“…Many studies have been performed on choosing good-quality oocytes and embryos for ICSI patients, and several articles have been published on growth factors, hormones, reactive oxygen species (ROS) production, apoptosis, and gap junctional complexes on the adjacent follicular cells in patients undergoing ICSI [8,[10][11][12][13][14][15]. Currently, there is increasing interest in signaling pathways (e.g., Wnt, Hedgehog, and Notch pathways) that are important for developing oocytes.…”

An update on primary ovarian insufficiency

“…They share a coincident primary structure and spatio-temporal expression pattern in ovary [40]. The roles of the two proteins in follicle growth and development can be co-operative but with species-dependent granulosa cell responses [41].…”

“…According to a research using GDF-9 null mouse model, while a complete loss of GDF-9 does not impact male fertility, homozygous females were infertile [52]. Homozygous GDF-9 null female mice present significantly smaller ovaries than wild type, probably because the granulosa cells lost mitotic ability and the follicle growth is blocked at the primary one-layer follicle stage [40,53]. Eight SNPs were uncovered across the coding region of GDF-9 gene [54,55], in which GDF-9 S77F and GDF-9 S109R were directly associated with sterility phenotype in ewes [5456].…”