title: Comparison of Genome-Wide and Gene-Specific DNA Methylation Profiling in First-Trimester Chorionic Villi From Pregnancies Conceived With Infertility Treatments.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Barlow
authors.affiliation: 1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.affiliation: 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.|3 UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Erica T
authors.initials: ET
authors.lastname: Wang
authors.affiliation: 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Bora
authors.initials: B
authors.lastname: Lee
authors.affiliation: 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Akhlaghpour
authors.affiliation: 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.|3 UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Kroener
authors.affiliation: 3 UCLA School of Medicine, Los Angeles, CA, USA.|4 Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.affiliation: 5 Institute for Translational Genomics and Population Sciences, LA Biomed/Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: 5 Institute for Translational Genomics and Population Sciences, LA Biomed/Harbor-UCLA Medical Center, Torrance, CA, USA.
authors.forename: Yii-der I
authors.initials: YI
authors.lastname: Chen
authors.affiliation: 1 Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.|3 UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.affiliation: 2 Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.|3 UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: Margareta D
authors.initials: MD
authors.lastname: Pisarska
mesh_terms: D000328:Adult; D064190:Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D056426:Genetic Loci; D006801:Humans; D007246:Infertility / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism
chemical_list: C118056:CXCL14 protein, human; D019743:Chemokines, CXC; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C491492:RIMS1 protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; C577339:ANAPC2 protein, human; D064190:Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome; D019204:GTP-Binding Proteins
keywords: IVF; NIFT; PTCRA; epigenetics; placenta