Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
DNA methylome reveals cellular origin of cell-free DNA in spent medium of human preimplantation embryos
Yidong Chen, … , Lu Wen, Jin Huang
Yidong Chen, … , Lu Wen, Jin Huang
Published June 15, 2021
Citation Information: J Clin Invest. 2021;131(12):e146051. https://doi.org/10.1172/JCI146051.
View: Text | PDF
Research Article Genetics Reproductive biology Article has an altmetric score of 15

DNA methylome reveals cellular origin of cell-free DNA in spent medium of human preimplantation embryos

  • Text
  • PDF
Abstract

The discovery of embryonic cell–free DNA (cfDNA) in spent embryo culture media (SECM) has brought hope for noninvasive preimplantation genetic testing. However, the cellular origins of SECM cfDNA are not sufficiently understood, and methods for determining maternal DNA contamination are limited. Here, we performed whole-genome DNA methylation sequencing for SECM cfDNA. Our results demonstrated that SECM cfDNA was derived from blastocysts, cumulus cells, and polar bodies. We identified the cumulus-specific differentially methylated regions (DMRs) and oocyte/polar body–specific DMRs, and established an algorithm for deducing the cumulus, polar body, and net maternal DNA contamination ratios in SECM. We showed that DNA methylation sequencing accurately detected chromosome aneuploidy in SECM and distinguished SECM samples with low and high false negative rates and gender discordance rates, after integrating the origin analysis. Our work provides insights into the characterization of embryonic DNA in SECM and provides a perspective for noninvasive preimplantation genetic testing in reproductive medicine.

Authors

Yidong Chen, Yuan Gao, Jialin Jia, Liang Chang, Ping Liu, Jie Qiao, Fuchou Tang, Lu Wen, Jin Huang

×

Figure 5

DNA mixing analysis.

Options: View larger image (or click on image) Download as PowerPoint
DNA mixing analysis.
(A) Pie charts depicting the results of the simulat...
(A) Pie charts depicting the results of the simulated DNA mixing experiment. Different percentages of DNA methylation data of the polar body (the MII oocyte), ICM/TE, and cumulus cells were mixed, including 100% input from 1 of the 3 components (100% input), 50% input from each of 2 components (50% + 1 input), 75% input of 1 component plus 25% input of 1 other component (75% + 1 input), 50% input of 1 component plus 25% each of the other 2 components (50% + 2 input), and 75% input of 1 component plus 12.5% each of the other 2 components (75% + 2 input). The input percentages and the predicted percentages are shown for comparison. (B) Correlations between the predicted and input component fractions of the simulated DNA mixing experiment. The 2-tailed Mann-Whitney-Wilcoxon test was used to assess significance.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 1 news outlets
Posted by 5 X users
Referenced in 1 patents
60 readers on Mendeley
See more details