Frontiers in Cell and Developmental Biology (Jul 2021)
Comparison of Genome-Wide DNA Methylation Profiles of Human Fetal Tissues Conceived by in vitro Fertilization and Natural Conception
- Ye Liu,
- Ye Liu,
- Ye Liu,
- Xinzhu Li,
- Xinzhu Li,
- Xinzhu Li,
- Songchang Chen,
- Songchang Chen,
- Songchang Chen,
- Li Wang,
- Li Wang,
- Yajing Tan,
- Yajing Tan,
- Xiaocui Li,
- Lin Tang,
- Junyu Zhang,
- Dandan Wu,
- Dandan Wu,
- Yanting Wu,
- Yanting Wu,
- Yanting Wu,
- Xinmei Liu,
- Xinmei Liu,
- Xinmei Liu,
- Yimin Zhu,
- Jianzhong Sheng,
- Jianzhong Sheng,
- Jianzhong Sheng,
- Jiexue Pan,
- Jiexue Pan,
- Jiexue Pan,
- Li Jin,
- Li Jin,
- Li Jin,
- Hefeng Huang,
- Hefeng Huang,
- Hefeng Huang,
- Hefeng Huang,
- Hefeng Huang
Affiliations
- Ye Liu
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Ye Liu
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, China
- Ye Liu
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Xinzhu Li
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Xinzhu Li
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, China
- Xinzhu Li
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Songchang Chen
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, China
- Songchang Chen
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Songchang Chen
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Li Wang
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Li Wang
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Yajing Tan
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Yajing Tan
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Xiaocui Li
- Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
- Lin Tang
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Junyu Zhang
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Dandan Wu
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Dandan Wu
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Yanting Wu
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Yanting Wu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Yanting Wu
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- Xinmei Liu
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Xinmei Liu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Xinmei Liu
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- Yimin Zhu
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, China
- Jianzhong Sheng
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, China
- Jianzhong Sheng
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Jianzhong Sheng
- Department of Pathology and Pathphysiology, School of Medicine, Zhejiang University, Hangzhou, China
- Jiexue Pan
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Jiexue Pan
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Jiexue Pan
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- Li Jin
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Li Jin
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Li Jin
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- Hefeng Huang
- International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Hefeng Huang
- Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, China
- Hefeng Huang
- Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China
- Hefeng Huang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
- Hefeng Huang
- Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China
- DOI
- https://doi.org/10.3389/fcell.2021.694769
- Journal volume & issue
-
Vol. 9
Abstract
BackgroundAssisted reproductive technology (ART) might induce adverse pregnancy outcomes and increase the risk of metabolic diseases in offspring’ later life with unknown reasons. Here we evaluated the global methylation level and methylation profile of fetal tissue from elective terminations of pregnancy (ETP) after natural conception and multifetal pregnancy reduction (MFPR) after in vitro fertilization and embryo transfer (IVF-ET).ResultsGlobal methylation levels were comparable between the fetal tissue of ETP after natural conception group and MFPR after IVF-ET group. The methylation levels were lower in the hypermethylated regions of the MFPR group than in the ETP group, while the methylation levels were higher in the hypomethylated regions of the MFPR group. Heatmap visualization and hierarchical clustering of the candidate differentially methylated regions (DMRs) showed differences between the DMRs in the ETP and MFPR samples. We identified 196 differentially methylated regions that matched 164 genes between the ETP and MFPR groups. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, skeletal system morphogenesis and diabetes mellitus ranked first. Ingenuity Pathway Analysis (IPA) revealed 8 diseases and functional annotations associated with IVT-ET. In the MFPR group, the final validation showed lower methylation levels in gene bodies of bone morphogenetic protein 4 (BMP4), higher methylation levels in the 1st exon and 5′UTR of thyroid peroxidase (TPO), and higher methylation levels in TSS1500 and TSS200 of interleukin 1 beta (IL1B).ConclusionsART does not alter global DNA methylation level, but influences DNA methylation variation in specific regions of human fetus in the early stage of life. Further studies are warranted to clarify the potential role of DNA methylation alterations in the gene expression profile.
Keywords
- IVF-ET
- DNA methylation
- fetal tissue
- multiembryo transfer
- developmental origins of health and disease
