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Age-dependent alterations in the signaling patway involved in oocyte activation.



Female reproductive aging is characyterized by the reduction of quality and quantity of ovarian follicle pool. This condition jeopardizes the production of oocytes competent for fertilization and embryi development. Following ovulation, mammallian oocytes are arrested at metaphase of the second meiotic division. Interaction with sperm or exposure to parthenogenetic agents triggers the activation of a calcium dependent pathway leading to meiosis resumption and entry into the first embryonic cell cycle. In this study we evaluated the hypotesis that the reduced devlopmental competence of "old" oocytes might be related to the reduced ability to stimulate signalling patways underlying oocyte activation. Since a key component of this pathway is the protein kinase C (PKC), we hypothesized that "old" oocytes fail in activating correctly this enzyme. To this end, we compared the effect of SrCL2, a parthenogenetic agent, on ovulated oocytes collected from "young" and old mice. Analysis of the kinetic of meiotic progression , revealed a significant delay in meiosis resumption and a reduced percentage of pronuclei formation in oocytes from old mice. This change was associated with a reduced expression of the calcium-dependent PKC isoforms monitored by means of Western blotting analysis. Moreover, old oocytes were characterized by an altered pattern of PCK activation. BAsed on present results, we suggest that oocytes produced during advanced reproductive aging may suffer from an incorrect storage of PKC during oogenesis that can impair the process of oocytes activation. Since age -dependent changes in PKC activation were found also in endpthelial and neuronal cells our data support the idea that mechanism underlying aging of germ cells resembles those present in somatic cells. In conclusion, present study might contribute to the knowledge of molecular markers of oocyte aging that could be helpful for setting new approches in IVF treatments of old patients

Year: 2006
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