EPIGENETIC AND ART

The embryonic development is regulated by genetic information that is inherited from both the sperm and the oocyte. Upon fertilization, a major epigenetic reprogramming of the parental genomes is required to fine tune the embryonic development. This epigenetic reprogramming includes a large panel of biological mechanisms: erasing of the gametic modifications, paternal genome demethylation, DNA methylation, histone modification, RNA-mediated transcriptional mechanisms (9-11). In addition, another epigenetic phenomenon, crucial for embryonic development, controls the expression of only one of the two inherited parental alleles for a subset of genes: the genomic imprinting (1,2; 17-19).

These epigenetic modifications are sensitive to the external environment and to the parental acquired inheritance and lifestyle (e.g. predisposition to diabetes and metabolic dysregulations). In ART treatments, various procedures, including the use of synthetic culture media, can disrupt the epigenetic reprogramming (12-19).

The current state of evidence shows that the embryo culture conditions can affect the global DNA methylation, the chromatin remodeling, the histone modifications, the retroviral silencing, the gene expression, the X-inactivation and the genomic imprinting (2-4). New and ongoing research is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases like Angelman Syndrome (AS), Beckwith‐Widemann Syndrome (BWS) and Prader‐Willi Syndrome (PWS) has been reported after the use of ART (5-8).

In conclusion the literature on epigenetic regulation in early embryo development reinforce the point that preimplantation development is a dynamic period of epigenetic reprogramming and that suboptimal embryo culture conditions can produce epigenetic alterations (2). In vitro, while it is possible to grow blastocysts that appears morphologically normal, some in reality are epigenetically compromised.

The AneVivo procedure enables the embryo development inside the women’s reproductive tract. This approach, as close as possible from the natural conception conditions, may reduce the occurrence of epigenetic alterations.

 

Glossary:

Epigenetics is the science referred to the modifications that does not affect at the DNA sequence of the individual per se, but to it’s genetic expression. Those modifications are potentially heritable at the cellular level.

DNA methylation is the modification of cytosines within CpG dinucleotides that is typically associated with gene silencing. (embryo culture and epigenetics, Brenna A. Market Velker, Mellissa R.W. Mann, Methods in Molecular biology, 2012)

Genomic imprinting is an epigenetic phenomenon whereby certain genes are expressed exclusively from one parental allele. Of significance is that many imprinted genes play critical roles in the development of the embryo, and their misregulation has been linked to the development of human imprinting disorders, such as Angelman syndrome (AS) and Beckwith-Wiedemann syndrome (BWS).

 

References:

  1. John Huntriss, Cambridge University Press, 2010.
  2. Velker, Mann, 2012, Methods in Molecular biology
  3. Shi, Haaf , 2012, Mol Reprod Dev
  4. Zaitseva, Krivokharchenko, 2007, Mol Reprod Dev
  5. Cox, 2002, Am J. Hum Genet
  6. De Baun, Feinberg , 2003,  Am J Hum Genet
  7. Ludwig, 2005, Med. Genet
  8. Stutdiffe, 2006, Human Reprod
  9. Mann, 2004, Development
  10. Li , 2005, Mol Human Reprod
  11. Fauque, 2007, BMC Dev Biol
  12. Biggers, Summers, 2008, Fertil Steril.
  13. Bavister, 1995, Human Reprod Update
  14. Dumoulin, 1999, Human Reprod
  15. Fischer,  Bavister, 1993, J Reprod Fertil
  16. Orsi, Leese,2001, Mol Reprod Dev
  17. Montfoort, Hanssen, 2012, Human Reproduction
  18. Camprubi, 2010, Rev Asoc Est Biol Rep
  19. Weaver, Bartolomei, 2009, Mamm Genome
  20. Davies Moore, 2012, N Engl J Med