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UBC Theses and Dissertations

Investigation into DNA methylation and gene expression profiles of imprinted regions in infants conceived via assisted reproductive technologies Vincent, Rebecca Naomi


A correlation has been found between babies born through assisted reproductive technologies (ARTs) and an increased risk of genomic imprinting disorders such as Beckwith-Wiedemann syndrome (BWS), Angelman syndrome (AS), and Silver-Russell syndrome (SRS), as well as other diseases in later life such as diabetes and obesity. In order to assess whether in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) impact the establishment of DNA methylation and/or gene expression patterns of imprinted regions, cord blood and placental tissue were collected from babies born after IVF and ICSI infertility treatments, as well as from naturally conceived controls. DNA methylation levels at the PLAGL1, KvDMR1 and PEG10 differentially methylated regions (DMRs) and their corresponding gene expression levels were analyzed due to their association with known imprinting disorders and influence on fetal and placental development. Methylation at the LINE-1 repetitive element was also analyzed as an indicator of global DNA methylation. We discovered a small, but significant increase in DNA methylation at the DMR of the tumor suppressor gene, PLAGL1, in cord blood from IVF pregnancies, as well as a lack of methylation at PEG10 in cord blood from all groups. We also found decreased levels of PLAGL1 gene expression in the IVF and ICSI groups, and decreased expression of KCNQ1OT1 and increased expression of IGF2 in IVF cord blood samples, which may suggest the disruption of an imprinted gene network involving chromosome 11p15.5. These findings indicate that the PLAGL1 DMR may be susceptible to epimutations in the ART population and could potentially lead to increased risk of imprinting disorders, intrauterine growth restriction and cancer susceptibility in ART conceived infants.

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