Marjonen, Heidi, Auvinen, Pauliina, Kahila, Hanna, Tsuiko, Olga, Koks, Sulev 
ORCID: 0000-0001-6087-6643, Tiirats, Airi, Viltrop, Triin, Tuuri, Timo, Soderstrom-Anttila, Viveca, Suikkari, Anne-Maria et al (show 3 more authors)
(2018)
rs10732516 polymorphism at the IGF2/H19 locus associates with genotype-specific effects on placental DNA methylation and birth weight of newborns conceived by assisted reproductive technology.
CLINICAL EPIGENETICS, 10 (1).
80-.
Abstract
<h4>Background</h4>Assisted reproductive technology (ART) has been associated with low birth weight of fresh embryo transfer (FRESH) derived and increased birth weight of frozen embryo transfer (FET)-derived newborns. Owing to that, we focused on imprinted insulin-like growth factor 2 (<i>IGF2</i>)/<i>H19</i> locus known to be important for normal growth. This locus is regulated by <i>H19</i> imprinting control region (ICR) with seven binding sites for the methylation-sensitive zinc finger regulatory protein (CTCF). A polymorphism rs10732516 G/A in the sixth binding site for CTCF, associates with a genotype-specific trend to the DNA methylation. Due to this association, 62 couples with singleton pregnancies derived from FRESH (44 IVF/18 ICSI), 24 couples from FET (15 IVF/9 ICSI), and 157 couples with spontaneously conceived pregnancies as controls were recruited in Finland and Estonia for genotype-specific examination. DNA methylation levels at the <i>H19</i> ICR, <i>H19</i> DMR, and long interspersed nuclear elements in placental tissue were explored by MassARRAY EpiTYPER (<i>n</i> = 122). Allele-specific changes in the methylation level of <i>H19</i> ICR in placental tissue (<i>n</i> = 26) and white blood cells (WBC, <i>n</i> = 8) were examined by bisulfite sequencing. Newborns' (<i>n</i> = 243) anthropometrics was analyzed by using international growth standards.<h4>Results</h4>A consistent trend of genotype-specific decreased methylation level was observed in paternal allele of rs10732516 paternal A/maternal G genotype, but not in paternal G/maternal A genotype, at <i>H19</i> ICR in ART placentas. This hypomethylation was not detected in WBCs. Also genotype-specific differences in FRESH-derived newborns' birth weight and head circumference were observed (<i>P</i> = 0.04, <i>P</i> = 0.004, respectively): FRESH-derived newborns with G/G genotype were heavier (<i>P</i> = 0.04) and had larger head circumference (<i>P</i> = 0.002) compared to newborns with A/A genotype. Also, the placental weight and birth weight of controls, FRESH- and FET-derived newborns differed significantly in rs10732516 A/A genotype (<i>P</i> = 0.024, <i>P</i> = 0.006, respectively): the placentas and newborns of FET-derived pregnancies were heavier compared to FRESH-derived pregnancies (<i>P</i> = 0.02, <i>P</i> = 0.004, respectively).<h4>Conclusions</h4>The observed DNA methylation changes together with the phenotypic findings suggest that rs10732516 polymorphism associates with the effects of ART in a parent-of-origin manner. Therefore, this polymorphism should be considered when the effects of environmental factors on embryonic development are studied.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Assisted reproductive technology, IVF, Fresh embryo transfer, Frozen embryo transfer, Imprinting, IGF2/H19, rs10732516, DNA methylation, Placenta, Birth weight |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 01 Feb 2019 11:31 |
| Last Modified: | 19 Jan 2023 01:05 |
| DOI: | 10.1186/s13148-018-0511-2 |
| Open Access URL: | https://doi.org/10.1186/s13148-018-0511-2 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3032117 |
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