The differential pathways of bone morphogenetic protein (BMP)-4 and -7 in the suppression of the bovine granulosa cell apoptosis

Abstract

Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-beta family, are crucial factors in follicular growth and development in the mammalian ovary. In this study, we examined the effects of BMP-4 and BMP-7 on granulosa cell apoptosis. Here, we report that BMP-7 suppresses granulosa cell apoptosis by inhibiting the release of caspase-activated DNase (CAD) via a mechanism which does not appear to be associated with the mitochondrial pathway, whereas BMP-4 inhibits the release of CAD. Our data provide the first evidence that BMP-4 and BMP-7 may inhibit granulosa cell apoptosis via different pathways.

XIAP: a potential determinant of ovarian follicular fate

“…In contrast, BMP4 may act as a potent XIAP inhibitor as treatment of bovine granulosa cells with BMP4 or BMP4 and BMP7 together did not affect XIAP levels ( Kayamori et al 2009). In addition, both BMPs stimulated expression of survivin, another IAP family member.…”

“…This may provide a mechanism for BMP7 regulation of XIAP; however, additional studies are required to confirm this. Furthermore, both BMP4 and BMP7 can promote granulosa cell survival, suggesting that these proteins may act through XIAP-dependent and -independent mechanisms (Kayamori et al 2009). …”

Ovarian Follicular Atresia

“…Essentially cFLIP is a "decoy" caspase, capable of oligomerizing with other caspase 8 molecules and cytokine receptors following ligandreceptor binding, but lacking the enzymatic activity to promote downstream activation of apoptotic pathways. Among the more recent molecules recognized for their anti-apoptotic effects are the bone morphogenetic proteins, BMP-4 and BMP-7 (Kayamori et al, 2009). These proteins are members of the transforming growth factor-beta superfamily and, at present, their anti-apoptotic actions within granulosa cells are attributed to an inhibition of caspase-activated DNase enzymes (Kayamori et al, 2009).…”

“…Among the more recent molecules recognized for their anti-apoptotic effects are the bone morphogenetic proteins, BMP-4 and BMP-7 (Kayamori et al, 2009). These proteins are members of the transforming growth factor-beta superfamily and, at present, their anti-apoptotic actions within granulosa cells are attributed to an inhibition of caspase-activated DNase enzymes (Kayamori et al, 2009). Thus, we are only beginning to understand the intricacies of the various growth factors and their intracellular signaling pathways as they relate to granulosa cell apoptosis, and ultimately follicular atresia.…”

The local regulation of folliculogenesis by members of the transforming growth factor superfamily and its relevance for advanced breeding programmes

“…Members of the BMP family, including BMP4, 6, 7 and 15 have been linked to reduced cumulus/mural granulosa cell apoptosis in cattle (Hussein et al, 2005;Kayamori et al, 2009). In bovine granulosa cells, BMP4 suppression of apoptosis was linked to the PI3K/PDK-1/Akt pathway whereas BMP7 suppression of apoptosis was linked to the PI3K/PDK-1/PKC pathway (Shimizu et al, 2012).…”