Evaluation of epigenetic marks in human embryos derived from IVF and ICSI.
BACKGROUND
It has long been appreciated that environmental cues may trigger adaptive responses. Many of these responses are a result of changes in the epigenetic landscape influencing transcriptional states and consequently altering phenotypes. In the context of human reproductive health, the procedures necessary for assisted reproduction may result in altered phenotypes by primarily influencing DNA methylation. Among the well-documented effects of assisted reproduction technologies (ART), imprinted genes appear to be frequently altered, likely owing to their reliance on DNA methylation to impose parent-specific monoallelic expression. However, the generality of the potential deregulation of DNA methylation in ART-derived human embryos has not been evaluated.


METHODS
In this study, we evaluate the genome-wide DNA methylation together with chromatin organisation in human embryos derived by either IVF (n = 89) or ICSI (n = 76). DNA methylation was assessed using an antibody against 5-methyl-cytidine, and chromatin organisation by DNA staining.


RESULTS
Irrespective of the ART procedure, similar errors were observed in both groups and abnormal chromatin was positively correlated (P < 0.001) with inappropriate DNA methylation. Development up to the blastocyst stage was consistent with normal DNA methylation and chromatin organisation, reinforcing the importance of epigenetic regulation to form the early lineages of the blastocyst. Most importantly, we found no evidence that ICSI blastocysts were more severely affected than those derived by IVF.


CONCLUSIONS
We conclude that ICSI does not lead to an increased incidence of epigenetic errors (DNA methylation and chromatin) compared with IVF.
Santos
Fátima
F
The Laboratory of Developmental Genetics and Imprinting, Babraham Research Campus, Cambridge CB22 3AT, UK.
Hyslop
Louise
L
Stojkovic
Petra
P
Leary
Christine
C
Murdoch
Alison
A
Reik
Wolf
W
Stojkovic
Miodrag
M
Herbert
Mary
M
Dean
Wendy
W
D015415:Biomarkers; D001755:Blastocyst / Q000737:chemistry / Q000473:pathology; D042002:Chromatin Assembly and Disassembly; D002869:Chromosome Aberrations / Q000196:embryology / Q000706:statistics & numerical data; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000737:chemistry* / Q000473:pathology; D047108:Embryonic Development; D044127:Epigenesis, Genetic; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D020554:Sperm Injections, Intracytoplasmic / Q000009:adverse effects*
D015415:Biomarkers