Discussion The present study shows that co administration of BMP 6 during selleck superovulation in aged female mice improves the number and developmental competence of oocytes ovu lated in an appropriate concentration. To our knowledge, this is the first demonstration of the direct effect of BMP 6 on ovarian response, oocyte quality Inhibitors,Modulators,Libraries and ovarian expression of angiogenic related Inhibitors,Modulators,Libraries factors of aged female using a mouse model. The mechanisms for positive Inhibitors,Modulators,Libraries effects of BMP 6 on ovarian response and oocyte quality of aged mice are as yet unknown. However, one can consider two aspects the first is the effect of BMP 6 itself and the second is the indirect effect of BMP 6 via the activation of ovarian angiogenesis.

BMP 6 was abundantly present in the granulosa cells of healthy follicle, not but in atretic follicles, of mammalian Inhibitors,Modulators,Libraries ovary and it prevents apoptosis of cumulus cells by oocytes in a paracrine manner. These results suggest that BMP 6 may be an important mediator to support healthy follicle growth in follicular development and ovarian function. This hypothesis has been supported by strong evidence of two in vivo studies by Campbell et al. and Sugiura et al. Campbell et al. showed that direct ovarian infusion of BMP 6 resulted in increase in ovarian inhibin A and estradiol secretion. Sugiura et al. reported that BMP 6 deficiency in female mice resulted in decreased fertility and less competent to completepreimplantation development. Due to this role of BMP 6, the administration of BMP 6 during superovulation may enhance not only ovarian response but also oocyte quality, subsequently resulting in increased embryo developmental competency.

Inhibitors,Modulators,Libraries An interesting finding in the present study was that BMP 6 treatment also stimulated the expression of Id 1 and VEGF in the ovary. This result is consistent with the report by Hogg et al. who showed that Id 1 expression was significantly increased following BMP 6 stimulation of granulosa cells in vitro. VEGF is a well known representative angiogenic factor sellectchem and it plays a critical role in the cyclic growth of ovarian follicles and mediates ovarian angiogenesis. Id proteins affect endothelial cells proliferation, migration, invasion, and differentiation and have an essential role in angiogenesis. Many studies demonstrated that Id 1 stimulates angiogenesis through the activation of VEGF. BMP 6 results in an advance in the time of the LH surge and LH surge have some direct effects on angiogenesis to induce a series of cellular and biochemical processes that culminate in ovulation. In this regard, it can be postulated that the beneficial effect of BMP 6 on oocyte quality and ovarian response may be resulted from the activation of ovarian angiogenesis via up regulation of ovarian Id 1 and VEGF expression.