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Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments

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Abstract

Background

Assisted reproductive technologies are associated with altered methylation in term placenta. However, it is unclear whether methylation patterns are the result of fertility treatments or intrauterine environment. Thus, we set out to determine whether there are differences in the first-trimester placenta that may be altered by the underlying fertility treatments. Genome-wide DNA methylation analyses from chorionic villus sampling (CVS) from matched singleton pregnancies conceived using in vitro fertilization (IVF), non-IVF fertility treatment (NIFT), or those conceived spontaneously were performed using Illumina Infinium HumanMethylation450 BeadChip from 15 matched CVS samples. Nanofluidic quantitative polymerase chain reaction (qPCR) of differently methylated genes was performed in a confirmatory cohort of 23 IVF conceptions and 24 NIFT conceptions.

Results

Global methylation was similar among the IVF, NIFT, and spontaneous conceptions. However, differential methylation from IVF and NIFT pregnancies was present at 34 CpG sites, which was significantly different. Of those, 14 corresponded to known genes, with methylation changes detected at multiple loci in 3 genes, anaphase-promoting complex subunit 2 (ANAPC2), C-X-C motif chemokine ligand 14 (CXCL14), and regulating synaptic membrane exocytosis 1 (RIMS1). Nanofluidic qPCR of differentially methylated genes identified pre T-cell antigen receptor alpha (PTCRA) to be significantly downregulated in IVF versus NIFT conceptions.

Conclusion

Although global methylation patterns are similar, there are differences in methylation of specific genes in IVF compared to NIFT conceptions, leading to altered gene expression. PTCRA was differentially methylated and downregulated in IVF conceptions, warranting further investigation. It remains to be determined whether these changes affect placentation and whether it is due to the more profound underlying infertility requiring IVF, yet these data provide unique insight into the first-trimester placental epigenome.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Ning Xu PhD, Jinrui Cui MS & Mark O. Goodarzi MD, PhD

  2. Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Gillian M. Barlow PhD, Erica T. Wang MD, MAS, Bora Lee PhD, Marzieh Akhlaghpour BS, Lindsay Kroener MD & Margareta D. Pisarska MD

  3. UCLA School of Medicine, Los Angeles, CA, USA

    Erica T. Wang MD, MAS, Lindsay Kroener MD, John Williams III MD, Mark O. Goodarzi MD, PhD & Margareta D. Pisarska MD

  4. Division of Maternal Fetal Medicine, Department of Obstetrics and Gyne-cology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    John Williams III MD

  5. Institute for Translational Genomics and Population Sciences, LA Biomed/ Harbor-UCLA Medical Center, Torrance, CA, USA

    Jerome I. Rotter MD & Yii-der I. Chen PhD

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  1. Ning Xu PhD
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  2. Gillian M. Barlow PhD
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Correspondence to Margareta D. Pisarska MD.

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Xu, N., Barlow, G.M., Cui, J. et al. Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments. Reprod. Sci. 24, 996–1004 (2017). https://doi.org/10.1177/1933719116675056

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