Title: Placental imprinting variation associated with assisted reproductive technologies and subfertility.
Authors: Litzky, Julia F; Deyssenroth, Maya A; Everson, Todd M; Armstrong, David A; Lambertini, Luca; Chen, Jia; Marsit, Carmen J
Published In Epigenetics, (2017 08)
Abstract: Infertility affects one in 6 couples in developed nations, resulting in an increasing use of assisted reproductive technologies (ART). Both ART and subfertility appear to be linked to lower birth weight outcomes, setting infants up for poor long-term health. Prenatal growth is, in part, regulated via epigenetically-controlled imprinted genes in the placenta. Although differences in DNA methylation between ART and control infants have been found, it remains unclear whether these differences are due to the ART procedures or to the underlying parental subfertility and how these methylation differences affect imprinted gene expression. In this study, we examined the expression of 108 imprinted genes in placental tissues from infants born to subfertile parents (n = 79), matched naturally-conceived controls (n = 158), and infants conceived using in vitro fertilization (IVF, n = 18). Forty-five genes were identified as having significantly different expression between the subfertile infants and controls, whereas no significant differences were identified between the IVF and control groups. The expression of 4 genes-IGF2, NAPIL5, PAX8-AS1, and TUBGCP5-was significantly downregulated in the IVF compared with the subfertile group. Three of the 45 genes significantly dysregulated between subfertile and control placentae-GRB10, NDN, and CD44 -were found to have a significant positive correlation between expression and birth weight. Methylation levels for these 3 genes and 4 others-MKRN3, WRB, DHCR24, and CYR61-were significantly correlated with expression. Our findings indicate that epigenetic differences in placentas resulting from IVF pregnancies may be related to the underlying subfertility in parents using IVF rather than the IVF procedure itself.
PubMed ID: 28621618
MeSH Terms: Adult; Case-Control Studies; Cysteine-Rich Protein 61/genetics; Cysteine-Rich Protein 61/metabolism; DNA Methylation*; Female; Fertilization in Vitro/adverse effects*; GRB10 Adaptor Protein/genetics; GRB10 Adaptor Protein/metabolism; Genomic Imprinting*; Humans; Hyaluronan Receptors/genetics; Hyaluronan Receptors/metabolism; Infant, Newborn; Infertility/genetics*; Insulin-Like Growth Factor II/genetics; Insulin-Like Growth Factor II/metabolism; Male; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Oxidoreductases Acting on CH-CH Group Donors/genetics; Oxidoreductases Acting on CH-CH Group Donors/metabolism; PAX8 Transcription Factor/genetics; PAX8 Transcription Factor/metabolism; Placenta/metabolism*; Pregnancy; Ribonucleoproteins/genetics; Ribonucleoproteins/metabolism; Tumor Suppressor Proteins/genetics; Tumor Suppressor Proteins/metabolism