Assisted reproductive technologies do not enhance the variability of DNA methylation imprints in human.
BACKGROUND Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are believed to destabilise genomic imprints. An increased frequency of Beckwith-Wiedemann syndrome in children born after ART has been reported. Other, mostly epidemiological, studies argue against this finding. OBJECTIVE To examine the effect of ART on the stability of DNA methylation imprints, DNA was extracted from maternal peripheral blood (MPB), umbilical cord blood (UCB) and amnion/chorion tissue (ACT) of 185 phenotypically normal children (77 ICSI, 35 IVF, and 73 spontaneous conceptions). Using bisulfite based technologies 10 differentially methylated regions (DMRs) were analysed, including KvDMR1, H19, SNRPN, MEST, GRB10, DLK1/MEG3 IG-DMR, GNAS NESP55, GNAS NESPas, GNAS XL-alpha-s and GNAS Exon1A. RESULTS Methylation indices (MI) do not reveal any significant differences at nine DMRs among the conception groups in neither MPB, UCB nor in ACT. The only slightly variable DMR was that of MEST. Here the mean MI was higher in UCB and MPB of IVF cases (mean MI+/-SD: 0.41+/-0.03 (UCB) and 0.40+/-0.03 (MPB)) compared to the ICSI (0.38+/-0.03, p=0.003 (UCB); 0.37+/-0.04, p=0.0007 (MPB)) or spontaneous cases (0.38+/-0.03, p=0.003 (UCB); 0.38+/-0.04, p=0.02 (MPB)). Weak but suggestive correlations between DMRs were, however, found between MPB, UCB and ACT. CONCLUSION This study supports the notion that children conceived by ART do not show a higher degree of imprint variability and hence do not have an a priori higher risk for imprinting disorders.
Tierling
Sascha
S
Universität des Saarlandes, FR 8.3 Biowissenschaften, Genetik/Epigenetik, Postfach 151150, D-66041 Saarbrücken, Germany. s.tierling@mx.uni-saarland.de
Souren
Nicole Y
NY
Gries
Jasmin
J
Loporto
Christina
C
Groth
Marco
M
Lutsik
Pavlo
P
Neitzel
Heidemarie
H
Utz-Billing
Isabelle
I
Gillessen-Kaesbach
Gabriele
G
Kentenich
Heribert
H
Griesinger
Georg
G
Sperling
Karl
K
Schwinger
Eberhard
E
Walter
Jörn
J
D000650:Amnion / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002823:Chorion / Q000378:metabolism; D002864:Chromogranins; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D051383:GRB10 Adaptor Protein / Q000235:genetics; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D027724:Reproductive Techniques, Assisted; D017422:Sequence Analysis, DNA; D055517:snRNP Core Proteins / Q000235:genetics
D002135:Calcium-Binding Proteins; D002864:Chromogranins; C512941:DLK1 protein, human; C096358:GRB10 protein, human; C094335:H19 long non-coding RNA; D036341:Intercellular Signaling Peptides and Proteins; C485621:KCNQ1OT1 long non-coding RNA, human; D008565:Membrane Proteins; D024642:Potassium Channels, Voltage-Gated; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C103637:mesoderm specific transcript protein; D055517:snRNP Core Proteins; D051383:GRB10 Adaptor Protein; D004247:DNA; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs