From Cell Death to Embryo Arrest: Mathematical Models of Human Preimplantation Embryo Development

Human preimplantation embryos exhibit high levels of apoptotic cells and high rates of developmental arrest during the first week in vitro. The relation between the two is unclear and difficult to determine by conventional experimental approaches, partly because of limited numbers of embryos. We app...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 98; no. 4; pp. 1655 - 1660
Main Authors Hardy, K., Spanos, S., Becker, D., Iannelli, P., Winston, R. M. L., Stark, J.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 13.02.2001
National Acad Sciences
The National Academy of Sciences
Subjects
Apoptosis
Biological Sciences
Biology
Blastocyst
Cell death
Cell nucleus
Cells
DNA Fragmentation
Embryo Loss
Embryonic and Fetal Development
Embryonic cells
Embryonic Development
Embryonic mortality
Embryos
Female
Humans
Mathematical Computing
Mathematical models
Models, Biological
Morula
Pregnancy
Probability
Retrospective Studies
Zygotes
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Summary:Human preimplantation embryos exhibit high levels of apoptotic cells and high rates of developmental arrest during the first week in vitro. The relation between the two is unclear and difficult to determine by conventional experimental approaches, partly because of limited numbers of embryos. We apply a mixture of experiment and mathematical modeling to show that observed levels of cell death can be reconciled with the high levels of embryo arrest seen in the human only if the developmental competence of embryos is already established at the zygote stage, and environmental factors merely modulate this. This suggests that research on improving in vitro fertilization success rates should move from its current concentration on optimizing culture media to focus more on the generation of a healthy zygote and on understanding the mechanisms that cause chromosomal and other abnormalities during early cleavage stages.
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Communicated by Paul Nurse, Imperial Cancer Research Fund, London, United Kingdom
To whom reprint requests should be addressed. E-mail: k.hardy@ic.ac.uk.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.98.4.1655