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DNA methylation profile of liver of mice conceived by in vitro fertilization

Published online by Cambridge University Press:  14 June 2021

Saúl Lira-Albarrán ,
Xiaowei Liu ,
Seok Hee Lee  and
Paolo Rinaudo Open the ORCID record for Paolo Rinaudo [Opens in a new window]
Saúl Lira-Albarrán
Affiliation:
Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA94143, USA
Xiaowei Liu
Affiliation:
Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA94143, USA
Seok Hee Lee
Affiliation:
Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA94143, USA
Paolo Rinaudo*
Affiliation:
Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, CA94143, USA
*
Address for correspondence: Paolo Rinaudo, Department of Obstetrics and Gynecology and Reproductive Sciences, Center for Reproductive Sciences, University of California, 513 Parnassus Avenue, HSW1464E, San Francisco, CA94143, USA. Email: rinaudop@obgyn.ucsf.edu
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Abstract

Offspring generated by in vitro fertilization (IVF) are believed to be healthy but display a possible predisposition to chronic diseases, like hypertension and glucose intolerance. Since epigenetic changes are believed to underlie such phenotype, this study aimed at describing global DNA methylation changes in the liver of adult mice generated by natural mating (FB group) or by IVF. Embryos were generated by IVF or natural mating. At 30 weeks of age, mice were sacrificed. The liver was removed, and global DNA methylation was assessed using whole-genome bisulfite sequencing (WGBS). Genomic Regions for Enrichment Analysis Tool (GREAT) and G:Profilerβ were used to identify differentially methylated regions (DMRs) and for functional enrichment analysis. Overrepresented gene ontology terms were summarized with REVIGO, while canonical pathways (CPs) were identified with Ingenuity® Pathway Analysis. Overall, 2692 DMRs (4.91%) were different between the groups. The majority of DMRs (84.92%) were hypomethylated in the IVF group. Surprisingly, only 0.16% of CpG islands were differentially methylated and only a few DMRs were located on known gene promoters (n = 283) or enhancers (n = 190). Notably, the long-interspersed element (LINE), short-interspersed element (SINE), and long terminal repeat (LTR1) transposable elements showed reduced methylation (P < 0.05) in IVF livers. Cellular metabolic process, hepatic fibrosis, and insulin receptor signaling were some of the principal biological processes and CPs modified by IVF. In summary, IVF modifies the DNA methylation signature in the adult liver, resulting in hypomethylation of genes involved in metabolism and gene transcription regulation. These findings may shed light on the mechanisms underlying the developmental origin of health and disease.

Keywords

In vitro fertilizationassisted reproductive technologiesepigeneticsDNA methylation
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 13 , Issue 3 , June 2022 , pp. 358 - 366
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Copyright
© The Author(s), 2021. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

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