Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles

Abstract

The synergetic process of folliculogenesis is mainly regulated by GDF-9 and BMP-15 as well as their receptors, such as BMPR2, TβR1 and BMPR1B. Expressions of these factors and the receptors are significant different among species. This study was designed to detect expression of GDF-9, BMP-15 and their receptors in mouse, porcine and human healthy follicles by immunohistochemistry. Three ages of human ovary were studied according to ovarian developmental schedule, i.e. gestational week (GW) 16, puberty (14 year-old) and adult (40 year-old). The results showed that both GDF-9 and BMP-15 were detectable in oocytes from primary follicles onward, besides, BMP-15 also presented in granulosa cells (GCs) and follicular follicle of mature follicles in mouse. However, they were maintained in oocytes and GCs from primordial to mature follicles in porcine except that GDF-9 was undetectable in GCs of mature follicles. For human ovary, GDF-9 presented in oocytes of primordial follicles in all samples, whereas BMP-15 was only observed in primordial follicle of adult ovary. Receptors, BMPR2, TβR1 and BMPR1B were found in oocytes and GCs of all follicles in mouse and porcine. In human, they were stained in oocytes from primordial follices but BMPR1B was not expressed in pubertal primordial follicles. Furthermore, we found that GDF-9, BMP-15 and three receptors distributed in adult corpus lutea. Collectively, our studies suggested that GDF-9, BMP-15 and their receptors might correlate with primordial follicular recruitment in pig and human. Positive expression of the receptors (BMPR2, TβR1 and BMPR1B)in primordial follicles of mouse ovaries indicated that these receptors might interact with others ligands besides GDF-9 and BMP-15 to regulate primordial follicular activity in mouse. Moreover, presence of GDF-9 in oocytes and BMP-15 in oocytes and GCs of mature follicles from mice and porcine elucidated coordinated roles of GDF-9 and BMP-15 in cumulus oophorus expansion. Additionally, expression of these factors in adult human corpus lutea suggested they play roles in corpus luteum activity.

Single-cell expression analysis of BMP15 and GDF9 in mature oocytes and BMPR2 in cumulus cells of women with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation

“…Transgenic deletions and other modifications in mice [8], sheep [9] and humans [10,11] have provided much of the new information on the mechanisms by which the oocyte affects follicular development [12,13]. The synergistic process of folliculogenesis is regulated mainly by GDF9 and BMP15 as well as their receptors (e.g., BMPR2, TR1, and BMPR1B) [14][15][16][17]. These two members of the TGF-β superfamily are coexpressed in human oocytes and play a fundamental role in granulosa cells steroidogenesis, ovulation, oocyte maturation, and embryo development in mammals [11,18,19].…”

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].…”

“…Many studies involving ovarian follicle functions have focused on the role of factors which are a part of the transforming growth factor beta (TGF-β) superfamily [1][2][3]. Amongst them, the bone morphogenetic protein-15 (BMP-15) and the growth differentiation factor-9 (GDF-9) deserve particular attention, as they participate in signalling pathways which control the development of ovarian follicles [3].…”

“…Amongst them, the bone morphogenetic protein-15 (BMP-15) and the growth differentiation factor-9 (GDF-9) deserve particular attention, as they participate in signalling pathways which control the development of ovarian follicles [3]. Recent research suggests that the factors affect the proliferation and differentiation of follicular somatic cells, steroidogenesis, deposition of the extracellular matrix, ovulation, and luteinization [2,4,5].…”

Growth and differentiation factor 9 promotes oocyte growth at the primary but not the early secondary stage in three-dimensional follicle culture

“…Whether GDF9 acts directly on the oocyte to induce follicle growth, indirectly through the granulosa cell or both, is not clear, given that both granulosa cells and oocytes in primary follicles express ALK5 [57][58][59][60][61] and BMPR2 [58,62], the reported type I [63,64] and II receptors for GDF9 [65], respectively. However, it is controversial whether ALK5 is the only type I receptor for GDF9 as Alk5 conditional knockout mice have no defects in follicular development and cumulus expansion [62], which is a distinct phenotype from Gdf9 null mice [17].…”