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Regular Article |
a Physiology of Human Reproduction Research Unit,
b Cellular Biology Unit,
c Medical Biochemistry Unit, and
d Veterinary Research Unit, Université Catholique de Louvain, 1200 Brussels and 1348 Louvain-la-Neuve, Belgium
ABSTRACT
Previous investigations have shown that maternal diabetes impairs rodent embryo development during the earliest phase of gestation. Exposure to high concentrations of glucose before implantation results in a decrease in the number of cells per embryo and in a concomitant increase in two nuclear markers of apoptosis, chromatin degradation and nuclear fragmentation. In the present study, we show that two intracellular effectors of apoptosis, caspase-3 and caspase-activated deoxyribonuclease (CAD), are involved in the embryotoxicity of high glucose. Using reverse transcription-polymerase chain reaction and immunocytochemistry, we first demonstrated that these two effectors were expressed in rat blastocysts. The two effectors were detected in all the cells of the blastocysts and the immuno-signals were excluded from the nuclei. Rat blastocysts were incubated for 24 h in either 6 mM or 28 mM glucose in the presence or absence of specific inhibitors (DEVD-CHO [10 µM] against caspase-3 and aurin [1 µM] against CAD). After incubation, blastocysts were examined for the proportion of nuclei showing signs of chromatin degradation or nuclear fragmentation. Addition of DEVD-CHO or aurin was found to inhibit the increase in chromatin degradation induced by high glucose. None of these two inhibitors prevented the increase in nuclear fragmentation triggered by excess glucose. Our data indicate that chromatin degradation and nuclear fragmentation are two nuclear damages that are induced separately by high glucose in rat blastocysts. Chromatin degradation is apparently mediated by the activation of caspase-3 and CAD.
1 Supported by Action de Recherche Concertée de la Direction Générale de la Recherche de la Communauté Française de Belgique (grant 96/01-96) and by the Juvenile Diabetes Foundation International. L.H. is the holder of a research fellowship from FRIA. S.P. is Chercheur Qualifié, FNRS.
2 Correspondence: Serge Pampfer, OBST 5330 Research Unit, University of Louvain, School of Medicine, 53 Avenue Mounier, B-1200 Brussels, Belgium. FAX: 32 2 764 5396; pampfer{at}obst.ucl.ac.be
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