title: In vitro maturation of oocytes is not associated with altered deoxyribonucleic acid methylation patterns in children from in vitro fertilization or intracytoplasmic sperm injection.
abstract: OBJECTIVE
  To study the possible transmission, to the next generation, of epigenetic defects associated with in vitro maturation (IVM) of human oocytes.
  
  
  METHODS
  Case-control study using epigenetic data.
  
  
  METHODS
  Two collaborating university departments.
  
  
  METHODS
  Eleven IVM newborns and 19 controls, conceived by conventional assisted reproduction.
  
  
  METHODS
  Chorionic villus and cord-blood sampling.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  IVM-induced epigenetic changes in offspring, if any, are relatively small in magnitude and/or infrequent.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: Galyna
authors.initials: G
authors.lastname: Pliushch
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schneider
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Schneider
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany.
authors.forename: Nady
authors.initials: N
authors.lastname: El Hajj
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Women's Hospital, Ruprecht Karls University, Heidelberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rösner
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Women's Hospital, Ruprecht Karls University, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Strowitzki
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Wuerzburg, Germany. Electronic address: thomas.haaf@uni-wuerzburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects; D005312:Fetal Blood / Q000378:metabolism; D018392:Genomic Imprinting; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques / Q000706:statistics & numerical data; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects
keywords: Bisulfite pyrosequencing; RAD51C; chorionic villus; cord blood; deep bisulfite sequencing; imprinting; in vitro maturation