Biomedical subjects

Bernadette Banrezes

Publications and source records attributed to Bernadette Banrezes.

3 recordsLinked to original sources

PubMed2006

Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term.

The Ca2+ oscillations initiated by the fertilizing sperm (but terminating concomitant with pronucleus formation) apparently ensure that the events constituting egg activation occur in the correct temporal order; early events (e.g., cortical granule exocytosis) require fewer oscillations than later events (e.g., recruitment of maternal mRNA). Whether the Ca2+ signaling events impact long-term development, in particular development to term, is unknown. Using fertilized eggs that have undergone the first few Ca2+ oscillations, we developed procedures that result either in inhibiting or stimulating the natural pattern of Ca2+ signaling of inseminated eggs. Although the incidence of development to the blastocyst stage is unaltered by these procedures, fewer offspring are born following embryo transfer, indicating that developmental competence of the blastocysts is reduced. Interestingly, embryo transfer experiments reveal that when the natural regime of Ca2+ oscillations is precociously interrupted, the incidence of implantation is compromised whereas hyper-stimulation of Ca2+ signaling events compromises post-implantation development. Moreover, although there was no major difference in the overall growth rates of the offspring, those obtained following hyper-stimulation exhibited a far greater variability in their weight. Analysis of global patterns of gene expression by microarray analysis revealed that approximately 20% of the transcripts are mis-regulated when too few oscillations are experienced by the embryo and EASE analysis indicates that genes preferentially involved in RNA processing and polymerase II transcription are differentially affected. In addition, a set of genes involved in cell adhesion is also mis-expressed and could thus be mechanistically linked to the observed reduced implantation. Only about 3% of the transcripts were mis-regulated following hyper-stimulation, and EASE analysis indicates that genes preferentially involved in metabolism are differentially affected. In toto, these results indicate that a range Ca2+ signaling events following fertilization (an excess or reduction) has long-term effects on both gene expression and development to term.

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PubMed2006

Egg activation is the result of calcium signal summation in the mouse.

Egg activation in mammals is caused by cytosolic Ca(2+) oscillations that are essential for development. However, despite increasing knowledge about signal transduction mechanisms, the functional linkage between frequency number, amplitude and duration of the Ca(2+) signal and the kinetics of pronucleus formation has not yet been defined. While a wide range of Ca(2+) signal parameters are efficient in causing egg activation, the basic rules governing how the egg integrates these signalling events are not yet clear. Thus, in the perspective of better understanding how the egg processes Ca(2+) signalling events, the objective of this study was to determine experimentally whether the efficiency of egg activation and the subsequent early developmental stages rely on Ca(2+) signalling summation. Non-fertilized, but freshly ovulated mouse eggs, were subjected to a series of repetitive Ca(2+) influxes of various patterns modulated by a non-invasive membrane electropermeabilization method. Using a combination of two suboptimal treatments we have shown that mouse eggs can sum up the effects caused by various patterns of intracellular Ca(2+) concentrations transient during the period of egg activation. In addition, overloading the intracellular milieu by repetitive Ca(2+) influxes did not seem to inhibit the process of activation. The kinetics of pronuclear formation among a population of eggs treated in the same conditions became accelerated when the total dose of Ca(2+) signal 'experienced' by the eggs was increased. The results suggested that summation of the biological effects of all Ca(2+) signals constitutes an important mode of Ca(2+) signal integration.

Animals↗

PubMed2005

Egg activation events are regulated by the duration of a sustained [Ca2+]cyt signal in the mouse.

Although the dynamics of oscillations of cytosolic Ca2+ concentration ([Ca2+]cyt) play important roles in early mammalian development, the impact of the duration when [Ca2+]cyt is elevated is not known. To determine the sensitivity of fertilization-associated responses [i.e., cortical granule exocytosis, resumption of the cell cycle, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, recruitment of maternal mRNAs] and developmental competence of the parthenotes to the duration of a [Ca2+]cyt transient, unfertilized mouse eggs were subjected to a prolonged [Ca2+]cyt change for 15, 25, or 50 min by means of repetitive Ca2+ electropermeabilization at 2-min intervals. The initiation and completion of fertilization-associated responses are correlated with the duration of time in which the [Ca2+]cyt is elevated, with the exception that autonomous CaMKII activity is down-regulated with prolonged elevated [Ca2+]cyt. Activated eggs from 25- or 50-min treatments readily develop to the blastocyst stage with no sign of apoptosis or necrosis and some implant. Ca2+ influx into unfertilized eggs causes neither Ca2+ release from intracellular stores nor rapid removal of cytosolic Ca2+. Thus, the total Ca2+ signal input appears to be an important regulatory parameter that ensures completion of fertilization-associated events and oocytes have a surprising degree of tolerance for a prolonged change in [Ca2+]cyt.

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