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Elevated cell death in human preimplantation embryos is one of the cellu-lar events compromising pregnancy rates after assisted reproductive tech-nology treatments. We therefore explored the molecular pathways regulating cell death at the blastocyst stage in human embryos cultured in vitro. Owing to limited availability of human embryos, these pathways were further characterized in mouse blastocysts. | ỊFEBS Journal Developmental consequences of alternative Bcl-x splicing during preimplantation embryo development Alagammal Perumalsamy1 Roxanne Fernandes1 2 3 Ingrid Lai1 2 3 Jacqui Detmar1 2 Sue Varmuza4 Robert F. Casper1 2 3 and Andrea Jurisicova1 2 3 1 SamuelLunenfeld Research Institute Mount Sinai Hospital Toronto Canada 2 Division of Reproductive Endocrinology and Infertility Department of Obstetrics Gynecology University of Toronto Canada 3 Department of Physiology University of Toronto Canada 4 Department of Celland System Biology University of Toronto Canada Keywords apoptosis Bcl-x blastocyst embryo in vitro culture Correspondence A. Jurisicova SamuelLunenfeld Research Institute Mount Sinai Hospital 25 Orde Street Room 6-1001-AJ Toronto ON Canada Fax 1 416 586 8588 Tel 1 416 586 4800 ext. 2052 E-mail jurisicova@lunenfeld.ca Received 23 June 2009 revised 10 November 2009 accepted 18 December 2009 doi 10.1111 j.1742-4658.2010.07554.x Elevated cell death in human preimplantation embryos is one of the cellular events compromising pregnancy rates after assisted reproductive technology treatments. We therefore explored the molecular pathways regulating cell death at the blastocyst stage in human embryos cultured in vitro. Owing to limited availability of human embryos these pathways were further characterized in mouse blastocysts. Gene expression studies revealed a positive correlation between the cell death index and the expression of Bcl-x transcript. Cell death activation in human blastocysts was accompanied by changes in Bcl-x splicing favoring production of Bcl-xS an activator of cell death. Expression of Bcl-xS was detected in a subset of human blastocysts that show particular clustering in dying and or dead cells. Altering the Bcl-xL Bcl-xS ratio in mouse embryos in antisense experiments confirmed that upregulation of Bcl-xS with concomitant downregulation of Bcl-xL compromised developmental potential and committed a subset of cells to undergoing cell .
