Expression and biological effects of bone morphogenetic protein-15 in the hen ovary

Abstract

The bone morphogenetic protein 15 (Bmp15) and growth differentiation factor 9 (Gdf9) genes are two members of the transforming growth factor-b superfamily. In mammals, these genes are known to be specifically expressed in oocytes and to be essential for female fertility. However, potential ovarian roles of BMPs remain unexplored in birds. The aim of the present work was to study for the first time the expression of Bmp15 in the hen ovary, to compare its expression pattern with that of Gdf9, and then to investigate the effects of BMP15 on granulosa cell (GC) proliferation and steroidogenesis. We found that chicken Bmp15 and Gdf9 genes were preferentially expressed in the ovary. We showed using in situ hybridization that Bmp15 and Gdf9 mRNAs were specifically localized in oocytes of all ovarian follicles examined. We also demonstrated using real-time quantitative RT-PCR that Bmp15 and Gdf9 expression was maintained during hierarchical follicular maturation in the gerrminal disc region and then progressively declined after ovulation. BMP15 was able to activate Smad1 (mothers against decapentaplegichomolog1) signaling pathway in hen GCs. Moreover, we showed a strong inhibitory effect of BMP15 on gonadotropin-induced progesterone production in hen GCs. This inhibitory effect was associated with a decrease in steroidogenic acute regulatory protein (STAR) level. Taken together, our results suggest that BMP15 may have a key role in the female fertility of birds.

Effect of Anti-Müllerian hormone (AMH) and bone morphogenetic protein 15 (BMP-15) on steroidogenesis in primary-cultured human luteinizing granulosa cells through Smad5 signalling

“…To our knowledge this is the first report on AMH effect on StAR protein levels, while previous studies in rat and hen granulosa cells have also shown an inhibitory effect of BMP-15 on FSH-induced StAR mRNA [43] and protein expression [44].…”

“…Recent studies in animals and human suggest that AMH attenuates the FSH-induced aromatase expression and estradiol production in the ovary [37][38][39][40][41], while AMH and AMHRII gene alterations correlate with follicular phase estradiol levels [42]. Moreover, results from animal models and immortalized human granulosa-lutein cells indicate that BMP-15 decreases the FSH-induced StAR protein levels and progesterone production [30,43,44].…”

Bone morphogenetic protein 2 inhibits FSH responsiveness in hen granulosa cells

“…Whereas a functional role of BMP15 in granulosa from preovulatory follicles has previously been proposed (Elis et al 2007), the studies described herein provide some of the first functional data from the avian ovary to implicate BMP family members in the regulation of granulosa cell function during early follicle development. Significantly, the expression of, and a functional role for, another BMP-related protein, anti-Mullerian hormone (AMH), has also been reported in the hen granulosa cells from prehierarchal follicles (Johnson et al 2008b).…”

The bioactivity of human bone morphogenetic protein-15 is sensitive to C-terminal modification: Characterization of the purified untagged processed mature region

“…Another recombinant form of BMP15 that has also appeared in the published literature is a BMP15 with a C-terminal Myc-His6 tag (Di Pasquale et al 2004). Although this form has been shown to be biologically active (Di Pasquale et al 2004;Fabre et al 2006;Elis et al 2007) it is likely that this form is also stabilised by the presence of the pro-region, and may exhibit compromised bioactivity if the modified mature region alone was used.…”