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a Department of Obstetrics and Gynecology, Women and Infants Hospital, Brown University, Providence, Rhode Island 02905
b Laboratory for Reproductive Medicine, Marine Biological Laboratory, Woods Hole, Massachusetts 02543
Aneuploidy underlies failed development and possibly apoptosis of some preimplantation embryos. We employed a haploid model in the mouse to study the effects of aneuploidy on apoptosis in preimplantation embryos. Mouse metaphase II oocytes that were activated with strontium formed haploid parthenogenetic embryos with 1 pronucleus, whereas activation of oocytes with strontium plus cytochalasin D produced diploid parthenogenetic embryo controls with 2 pronuclei. Strontium induced calcium transients that mimic sperm-induced calcium oscillations, and ploidy was confirmed by chromosomal analysis. Rates of development and apoptosis were compared between haploid and diploid parthenogenetic embryos (parthenotes) and control embryos derived from in vitro fertilization (IVF). Haploid mouse parthenotes cleaved at a slower rate, and most arrested before the blastocyst stage, in contrast to diploid parthenotes or IVF embryos. Developmentally retarded haploid parthenotes exhibited apoptosis at a significantly higher frequency than did diploid parthenotes or IVF embryos. However, diploid parthenotes exhibited rates of preimplantation development and apoptosis similar to those of IVF embryos, indicating that parthenogenetic activation itself does not initiate apoptosis during preimplantation development. These results suggest that haploidy can lead to an increased incidence of apoptosis. Moreover, the initiation of apoptosis during preimplantation development does not require the paternal genome.
1 This work was supported by grants from the National Institutes of Health (K081099) and by the Women and Infants Hospital/Brown Faculty Research Fund.
2 Correspondence: David L. Keefe, Department of Obstetrics and Gynecology, Brown University and Women & Infants Hospital, 101 Dudley Street, Providence, RI 02905. FAX: 401 453 7599; dkeefe{at}wihri.org
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