010. Coordinating the transition from egg to embryo in mammals
J. Carroll
Reproduction, Fertility and Development
16(supplement) 10 - 10
Published: 26 August 2004
Abstract
At fertilization of mammalian oocytes, the sperm induces a series of increases in the concentration of intracellular Ca2+. These Ca2+ oscillations trigger all the events of egg activation, including cortical granule exocytosis, completion of meiosis and entry into the first mitotic division. Thus, intracellular Ca2+ plays a pivotal role in coordinating the transition from egg to embryo. Our work is focussed on understanding how the oocyte prepares for fertilisation, how the Ca2+ oscillations are controlled and how Ca2+ stimulates signalling pathways that lead to optimal early embryonic development. In this lecture I will focus on the downstream pathways of Ca2+ signalling at fertilisation. Conventional Protein Kinase C (cPKC) is the major downstream target of Ca2+ in many cell functions. Using PKC-GFP fusion proteins we have found that cPKC is recruited to the membrane in a manner that is dependent on the frequency and amplitude of the Ca2+ oscillations. Recruitment of cPKC appears to promote the Ca2+ influx necessary to sustain the generation of long lasting Ca2+ oscillations. In other cell types cytosolic Ca2+ increases are known to stimulate mitochondrial respiration. We have found that maintenance of resting Ca2+ levels and sperm-induced Ca2+ oscillations are critically dependent on mitochondrial ATP production: a feature not shared by many cell types. Since Ca2+ release increases ATP consumption we investigated whether the Ca2+ transients increase mitochondrial activity so as to meet this increase in demand. Monitoring autofluorescence from NADH and flavoproteins reveals that Ca2+ transients stimulate a change in redox state of mitochondria, presumably by activating Ca2+-sensitive dehydrogenases of the TCA cycle. Thus, through activation of downstream pathways, including PKC, cyclin B degradation and mitochondrial activity, intracellular Ca2+ provides a signal that orchestrates the activation of early mammalian development.https://doi.org/10.1071/SRB04Abs010
© CSIRO 2004