Capturing sex-specific and hypofertility-linked effects of assisted reproductive technologies on the cord blood DNA methylome

Clinical Epigenetics

Research

William D. Fraser¹  Xiaojian Shao²  Marie-Michelle Simon³  Tony Kwan⁴  Guillaume Bourque⁴  Sophia Rahimi⁵  Josée Martel⁵  Donovan Chan⁵  Jacquetta Trasler⁶  Anick Bérard⁷ 

[1] Department of Obstetrics and Gynecology, Université de Sherbrooke and Centre de Recherche du CHUS, Sherbrooke, QC, Canada;Digital Technologies Research Centre, National Research Council Canada, Ottawa, ON, Canada;Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada;McGill University Genome Centre, Montreal, QC, Canada;McGill University Genome Centre, Montreal, QC, Canada;Department of Human Genetics, McGill University, Montreal, QC, Canada;Research Institute of the McGill University Health Centre, Montreal, QC, Canada;Research Institute of the McGill University Health Centre, Montreal, QC, Canada;Department of Human Genetics, McGill University, Montreal, QC, Canada;Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada;Department of Pediatrics, McGill University, Montreal, QC, Canada;Research Unit On Medications and Pregnancy, Research Centre, CHU Sainte-Justine, Montreal, Canada;Faculty of Pharmacy, Université de Montréal, Montreal, QC, Canada;Faculty of Medicine, Université Claude Bernard Lyon 1, Lyon, France;

关键词: Assisted reproductive technology;    Genomic imprinting;    Sex specific;    Infertility;    Hypofertility;    DNA methylation;    Cord blood;   

DOI  :  10.1186/s13148-023-01497-7

 received in 2022-09-12, accepted in 2023-05-02,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundChildren conceived through assisted reproduction are at an increased risk for growth and genomic imprinting disorders, often linked to DNA methylation defects. It has been suggested that assisted reproductive technology (ART) and underlying parental infertility can induce epigenetic instability, specifically interfering with DNA methylation reprogramming events during germ cell and preimplantation development. To date, human studies exploring the association between ART and DNA methylation defects have reported inconsistent or inconclusive results, likely due to population heterogeneity and the use of technologies with limited coverage of the epigenome. In our study, we explored the epigenetic risk of ART by comprehensively profiling the DNA methylome of 73 human cord blood samples of singleton pregnancies (n = 36 control group, n = 37 ART/hypofertile group) from a human prospective longitudinal birth cohort, the 3D (Design, Develop, Discover) Study, using a high-resolution sequencing-based custom capture panel that examines over 2.4 million autosomal CpGs in the genome.ResultsWe identified evidence of sex-specific effects of ART/hypofertility on cord blood DNA methylation patterns. Our genome-wide analyses identified ~ 46% more CpGs affected by ART/hypofertility in female than in male infant cord blood. We performed a detailed analysis of three imprinted genes which have been associated with altered DNA methylation following ART (KCNQ1OT1, H19/IGF2 and GNAS) and found that female infant cord blood was associated with DNA hypomethylation. When compared to less invasive procedures such as intrauterine insemination, more invasive ARTs (in vitro fertilization, intracytoplasmic sperm injection, embryo culture) resulted in more marked and distinct effects on the cord blood DNA methylome. In the in vitro group, we found a close to fourfold higher proportion of significantly enriched Gene Ontology terms involved in development than in the in vivo group.ConclusionsOur study highlights the ability of a sensitive, targeted, sequencing-based approach to uncover DNA methylation perturbations in cord blood associated with hypofertility and ART and influenced by offspring sex and ART technique invasiveness.

【 授权许可】

CC BY   
© The Author(s) 2023

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