Apoptotic cell death has been reported in human oocytes and preimplantation embryos under in vivo and in vitro
conditions. BCL-2 family proteins comprise both anti- and pro-apoptotic members, which are likely to play a key role
in controlling oocyte and early embryo survival. However, very limited data are available on their expression kinetics during
human early embryonic development. Using our DNA microarray data, we analyzed the expression pattern of 21
BCL-2 family genes in human mature MII oocytes, day 3 embryos and day 5/6 blastocysts from patients who underwent
in vitro fertilization (IVF). Selected genes were further validated by qRT-PCR and their subcellular localization analyzed
by immunofluorescence confocal microscopy. Our results suggest a switch from oocyte-inherited BCL-2 family transcripts,
such as BCL2L10, to embryo-produced transcripts after embryonic genome activation, including BIK, BCL2L11
and NOXA. Moreover, the pro-apoptotic gene BCL2L13 was constitutively expressed throughout human early embryonic
development. Remarkably, day 3 embryos expressed more BCL-2 pro-apoptotic genes than mature MII oocytes and day
5/6 blastocysts, suggesting that embryos at this stage are more prone to apoptosis. This is further supported by an absence
of cleaved Caspase-3 in the oocyte and its presence in the embryo. Using a drug that induces apoptosis (gambogic acid),
we were able to show activated Caspase-3 in the oocyte in addition to an alteration of BCL2L13 protein localization.
Similarly BCL2L13 localization was altered in degenerated oocytes. This study opens new perspectives for understanding
the molecular regulation of human oocyte and pre-implantation embryo survival and death.
Keywords: Apoptosis, BCL-2 family, blastocyst, early embryo, gambogic acid, human oocyte.
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