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UBC Theses and Dissertations

Investigation of methylation and gene expression in placenta of pregnancies conceived by assisted reproductive technology (ART) Sakian, Sina


With the increasing use of assisted reproductive techniques (ART) every year, concerns have been raised regarding the possible effect these procedures have on the health of the children procured by them. Although patients born via ART are usually healthy, studies have associated these procedures with increased incidence of low birth weight (LBW), chromosomal abnormalities, birth defects and imprinting disorders. No study has proposed a single defined cause for any of these defects in ART infants, however it is believed that they may be due to both the invasiveness of ART and to genetic defects that are at the root of the infertility in the parents. In this study, changes in the methylation of the H19 and IGF2 imprinting control region 1 (ICR1) were investigated for both ART (n=92) and naturally conceived controls (n=19) using pyrosequencing. Expression of H19 and IGF2 was also investigated for both the ART population (n=31) and controls (n=14) using quantitative real-time PCR. No significant changes in H19 or IGF2 methylation or gene expression were found between the ART groups and the natural conception group. Methylation levels at ICR1 for the IVF, ICSI and control cases were averaged at 49.3% ±3.4%, 49.6%±1.9% and 48.7%±1.7%, respectively. Compared to the controls IVF and ICSI patients both showed an increase in H19 gene expression (by a factor of 1.78±0.74 and 1.93±0.71, respectively) while showing a decrease (by a factor of 0.83±0.34 and 0.74±0.27, respectively) for the expression of IGF2; these differences were not proven significant using ANOVA (P > 0.05). The study did find, however, that the previously proposed H19 and IGF2 regulatory model is not a good indicator of how these two genes are controlled in human placenta. Comparing methylation analysis with expression analysis did not show the expected negative correlation implying that there may be other factors influencing the expression of H19 and IGF2 in human placental tissue. Although our results suggest that ART does not have a significant negative effect on H19 and IGF2 imprinting in the placenta, it merits further investigation looking at the regulation of these two genes in this tissue.

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