Abstract
To study the possible transmission, to the next generation, of epigenetic defects associated with invitro maturation (IVM) of human oocytes. Case-control study using epigenetic data. Two collaborating university departments. Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction. Chorionic villus and cord-blood sampling. Using bisulfite pyrosequencing, we have measured average methylation levels of 6 imprinted (LIT1, MEG, MEST, NESPas, PEG3, and SNRPN), 5 tumor-suppressor (APC, ATM, BRCA1, RAD51C, and TP53), 2 pluripotency (NANOG and OCT4), and 2 metabolic (LEP and NR3C1) genes, as well as 2 repetitive elements (ALU and LINE1) in 2 tissues of IVM and control neonates. Using deep bisulfite sequencing, we have determined methylation patterns of many individual DNA molecules to detect rare RAD51C epimutations (allele methylation errors). No statistically significant impact was found of IVM on chorionic villus and cord-blood DNA methylation at the studied developmentally important genes and interspersed repeats. The RAD51C epimutation rate was low (0.5% ± 0.1%) in all analyzed samples. IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.
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