Fertility and sterility · 2015
In vitro maturation of oocytes is not associated with altered deoxyribonucleic acid methylation patterns in children from in vitro fertilization or intracytoplasmic sperm injection.
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Pliushch Galyna, Schneider Eberhard, Schneider Tamara, El Hajj Nady, Rösner Sabine, Strowitzki Thomas, Haaf Thomas
Аннотация
OBJECTIVE: To study the possible transmission, to the next generation, of epigenetic defects associated with in vitro maturation (IVM) of human oocytes.
DESIGN: Case-control study using epigenetic data.
SETTING: Two collaborating university departments.
PATIENT(S): Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction.
INTERVENTION(S): Chorionic villus and cord-blood sampling.
MAIN OUTCOME MEASURE(S): 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).
RESULT(S): 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.
CONCLUSION(S): IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.
DESIGN: Case-control study using epigenetic data.
SETTING: Two collaborating university departments.
PATIENT(S): Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction.
INTERVENTION(S): Chorionic villus and cord-blood sampling.
MAIN OUTCOME MEASURE(S): 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).
RESULT(S): 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.
CONCLUSION(S): IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.