Eilander, M.S. (2012) Methylation of IGF2, SERPINA3, LINE-1 and intra-uterine growth restriction. thesis, Medicine.
Full text available on request.Abstract
Introduction: Intra-uterine growth restriction (IUGR) is associated with perinatal morbidity and mortality, and an increased risk of metabolic diseases in later life. The most important cause for IUGR is reduced uteroplacental blood flow. IGF2 has been shown to influence the growth of the placenta and the fetus. Transcription of a gene can be inhibited by binding a methylgroup, called methylation. Recent studies are focusing on methylation patterns of genes, and their association with IUGR. The methylation of IGF2, SERPINA3 and LINE-1 is changed in at term placentas of IUGR affected pregnancies. It is unknown whether this is a cause or a consequence of IUGR. Aims: The methylation levels of IGF2, SERPINA3 and LINE-1 in first trimester placentas were measured, to determine whether the changed methylation patterns in IUGR are already present before the appearance of IUGR. Materials and methods: Between 2004 and 2009 over 2000 women underwent a chorionic villous biopsy (CVB) because of maternal age or a risk of chromosomal deviations. From the patients with an available CVB (n=695), 35 IUGR affected pregnancies were selected. They were matched to two controls without pregnancy complications (n=70), based on their gestational age at the moment of CVB. DNA of the CVB’s was isolated and bisulfite treated. The DNA sequence of IGF2, SERPINA3 and LINE-1 was multiplied by PCR, with designed primers. The methylation levels were analysed by pyrosequencing. Results: For IGF2 and LINE-1 all samples had satisfactory measurements. 5 samples failed to get a satisfactory measurement for SERPINA3 and were excluded. Depending on the distribution of each methylation value, T-test and Mann-Whitney test showed no significant association between the methylation levels of IGF2, SERPINA3, LINE-1 and IUGR. Smoking and maternal age were not of influence on the methylation levels of IGF2, SERPINA3 and LINE-1. Hypertension had a significant influence on the methylation level of LINE-1, but not on IGF2 and SERPINA3. The 4th studied location of IGF2 showed a dichotomous distribution of methylation levels, not associated with IUGR, fetal gender, smoking, hypertension or maternal age. Conclusion: This study shows no relation between the methylation levels of IGF2, SERPINA3 and LINE-1 in first trimester placenta and the occurrence of IUGR later in the pregnancy. It is not possible to draw final conclusions on the role of methylation of the studied genes and the development of IUGR. The methylation changes can occur in a later stage of pregnancy thereby causing IUGR. Changed methylation in at term placentas can also be the result of a compensatory mechanisme for IUGR. More research regarding methylation levels throughout pregnancy and their influence on transcription is needed.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor: and Erwich, Dr. J.J.H.M. and Obstetrics & Gynaecology and UMCG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:02 |
| Last Modified: | 25 Jun 2020 11:02 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2176 |
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