April 12, 2016 – Single-cell embryos contain a set of maternal and paternal chromosomes, and as the embryo grows, daughter cells receive a copy of each. In a study published online today in Genome Research, researchers have discovered errors during the earliest stages of embryonic development can lead to entire sets of maternal and paternal chromosomes segregating into different cells, resulting in chimeric embryos.
"This is a novel fundamental insight into the origin of chimerism, a very rare condition in humans which can lead to birth defects," senior author Joris Vermeesh, from KU Leuven, said.
Previous studies involving in vitro fertilized (IVF) human embryos have demonstrated large fractions of embryos contain at least one cell with either whole or partial gains or losses of chromosomes. This chromosomal instability can lead to reduced fecundity and birth defects. To investigate in more detail, researchers from KU Leuven and elsewhere employed in vitro fertilization in cattle as a flexible system to study chromosomal changes in single embryonic cells.
Applying haplarithmisis, a method they previously developed, the researchers examined copy number and parental origin of chromosomes in single cells from 23 embryos. Nearly three-fourths of embryos examined contained at least one cell with either partial or whole chromosome aberrations, similar to findings in human in vitro fertilized embryos. Surprisingly, 39% of all embryos contained cells with abnormalities of entire sets of embryos, for example, cells with only one set of chromosomes, either maternal or paternal, or three sets (one maternal set plus two paternal sets, or vice versa). Many of these embryos resulted from fertilization errors, such as two sperm fertilizing a single egg. However, normally fertilized embryos also displayed this aberrant pattern. The researchers coined the cell division leading to the segregation of parental chromosomes "heterogoneic," or of differential parental origin.
The finding that normal fertilization can result in embryos containing cells with different parental sets of chromosomes is a new mechanism for chimerism, which was previously thought to occur only as the result of fertilization errors, for example, the fusion of multiple sperm or eggs to form an embryo.
"The presence of chimerism in human IVF embryos was never conceived," Vermeesch said. "Knowing this might occur may improve approaches for embryo selection and ultimately the success of IVF/preimplantation genetic diagnosis."
Scientists from KU Leuven, Ghent University, University of Tartu, and Wellcome Trust Sanger Institute contributed to this study. The study was funded by the Agency for Innovation by Science and Technology, the Research Foundation Flanders, the European Union's Research and Innovation funding program and the University of Leuven.
The authors are available for more information by contacting: Professor Joris Vermeesch, KU Leuven ([email protected]) or Sigrid Somers, Newsroom Chief & Chief Press Officer, KU Leuven ([email protected], +32 16 37 63 85 and + 32 16 32 40 08 [office], +32 4 75 87 40 08 [cell]).
Interested reporters may obtain copies of the manuscript via email from Peggy Calicchia, Administrative Assistant, Genome Research ([email protected], +1-516-422-4012).
About the article:
The manuscript will be published online ahead of print on 12 April 2016. Its full citation is as follows:
Destouni A, Zamani Esteki M, Catteeuw M, Tšuiko M, Dimitriadou E, Smits K, Kurg A, Van Soom A, Voet T, Vermeesch JR. 2016. Zygotes segregate entire parental genomes in distinct blastomere lineages causing cleavage stage chimerism and mixoploidy. Genome Res doi: 10.1101/gr.200527.115
About Genome Research:
Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine. Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
About Cold Spring Harbor Laboratory Press:
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. The Press is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public. For more information, visit our website at http://cshlpress.org/
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