reproduction - How might IVF (and related technologies) alter epigenetic marks?

I was reading up on KCNQ1, which encodes a voltage-gated potassium channel, and I discovered that it happens to be only maternally expressed. This is regulated by KCNQ1OT1, a non-coding RNA, which is also epigenetically regulated (expressed only paternally). Mutations in KCNQ1OT1 are associated with Beckwith-Wiedemann Syndrome (BWS).

Further reading led to the discovery that there are ART-related (assisted reproductive technology) cases of BWS due to loss of methylation at KCNQ1.

However, this article found epigenetic stability of KCNQ1OT1 methylation in cultured human embryonic stem cells, which leads me to think that KCNQ1 might also have been properly methylated.

So what exactly are assisted reproductive technologies doing that can disrupt inheritance of epigenetic marks (that culturing hESCs doesn't do)? (Is this understood for any gene?)

Answer

I was at a talk last year where some geneticists were starting to look at the effect of IVF techniques on genetic issues. Because of the work being done and the inclinations of the clients involved, this has not been studied very much. One presumes that since zygotes are still used, there will not be much epigenetic effects due to methylation patterns - its the same cell stocks being used in vitro and in vivo.

There may be an effect on genetics because the natural selection process. Spermatogenesis and oogenesis is a highly selective process; only a small fraction of the ova generated by the ovaries ever mature and a large percentage of sperm generated are not motile or have other irregularities. During fertilization, sperm competition obviously throws out all but one in 250 million. It also appears that there are processes in the fallopian tubes that can store the sperm for several (up to 5) days before fertilization.

So while its not strongly established one can see how various IVF processes vary from in vivo fertilization. This could have an impact on epigenetic factors, although different sperm vary genetically due to Meiosis and this would be a big source of genetic variation in the outcome.