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Developmental Regulation and In Vitro Culture Effects on Expression of DNA Repair and Cell Cycle Checkpoint Control Genes in Rhesus Monkey Oocytes and Embryos¹

The Fels Institute for Cancer Research and Molecular Biology,³ Department of Biochemistry,⁴ Temple University School of Medicine, Philadelphia, Pennsylvania 19140 The Wisconsin National Primate Research Center,⁵ University of Wisconsin, Madison, Wisconsin 53715

DNA repair is essential for maintaining genomic integrity, and may be required in the early embryo to correct damage inherited via the gametes, damage that arises during DNA replication, or damage that arises in response to exposure to genotoxic agents. The capacity of preimplantation stage mammalian embryos to repair damaged DNA has not been well characterized, particularly in primate embryos. In this study, we examined the expression of 48 mRNAs related to sensing different kinds of DNA damage, repairing that DNA damage, and controlling the cell cycle to provide an opportunity for DNA repair. The expression data reveal dynamic temporal changes, indicating a changing ability of the rhesus embryo to detect and repair different kinds of DNA damage. Low expression or overexpression of specific DNA repair genes may limit the ability of the embryo to respond to DNA damage at certain stages. Additionally, our data reveal that in vitro culture may lead to dysregulation of many such genes and a potentially impaired ability to repair DNA damage, thus affecting cellular viability and long-term embryo viability via effects on genome integrity. This effect of in vitro culture on nonhuman primate embryos may be relevant to assessing the potential advantages and disadvantages of prolonged in vitro culture of human embryos.

cell cycle control, DNA repair, embryo, gene expression, gene regulation, oocyte, primate

² Correspondence: Keith E. Latham, 3307 N. Broad Street, Philadelphia, PA 19140. FAX: 215 707 1454; klatham{at}temple.edu