Effect of Ovulation Stimulation on Epigenetic Pattern of Imprinted/Developmental Genes in NMRI Mice

Background: Genomic imprinting is an epigenetic phenomenonthat plays a critical role in normal development of embryo.It has been proven that deficient genomic imprinting can causeinfertility.Changes that occur in the hormonal profile, reproductivesystem and gametes of an organism during assisted reproductivetechnology (ART) can affect epigenetic events. The aimof this study was to evaluate the genetic and epigenetic changesin a few body organs after ovarian stimulation. For this, theexpression of three imprinting genes (H۱۹, Igf۲and Cdkn۱c),all of which have important roles in development of placentaand embryo.Materials and Methods: The epigenetic profile of their regulatoryregion in brain, lung, heart, liver, kidney, ovary and placentaof ۱۹-day-old female mice fetuses subjected to ovulationinduction were evaluated by qRT-PCR and ChIP methods.Results: Results showed altered gene expression in line withchanges in epigenetic pattern of their promoters in the ovulationstimulation group vs. normalcycle. H۱۹ gene decreasedsignificantly in lung, heart, liver, placenta and ovary of ovulationstimulation group in comparison to control fetuses. Howeverkidney showed increased levels of H۱۹ in mentioned experimentalgroup vs. control. Igf۲ showed significantly higherlevels of expression in brain and kidney andCdkn۱c showedsignificant increase in lung and significant decrease in placentaof ovarian stimulation group versus control fetuses.Conclusion: Disrupted gene expression pattern and epigeneticprofile of these imprinting genes may be the cause of lowweight syndrome in embryos or incomplete growth of organs.Also some problems like respiratory distress syndrome in ARTnewborns or urogenital deficiencies in ART born children maybe related to disruption of these genes expression in their lungand kidney, caused by ovarian stimulation.

کلیدواژه ها:

Epigenetic ، Genomic Imprinting ، Ovarian Stimulation