Scientists at the Wellcome Sanger Institute, the University of Cambridge and their collaborators have found that the placenta resembles that of a tumour, harbouring many of the same genetic defects found in childhood cancers.
The placenta
Within the first few days of embryogenesis, foetal and placental lineages spatially diverge. The placenta is very distinct from other human organs. Placentas can exhibit chromosomal aberrations that are confined to this organ and affect 1-2% of pregnancies. Dysfunction of the placenta contributes to the global burden of diseases and can cause harm to the mother and unborn child.
Placentas can exhibit chromosomal aberrations that are absent from the foetus. The basis of this genetic segregation (also known as confined placental mosaicism) remains unclear. While the clonal dynamics of human embryos cannot be studied prospectively, it is possible to reconstruct embryonic lineage relationships from somatic mutations.
Genomic landscape
In this study, published in Nature, researchers investigated the phylogeny of human placental cells. To achieve this, they reconstructed the phylogeny from somatic mutations using whole-genome sequencing data from 86 bulk placental samples and 106 microdissections of placental tissue. The samples were all taken from different areas of each organ.
The team found that each one of the biopsies was a genetically distinct clonal expansion. They also found that each biopsy had a genomic landscape similar to that of childhood cancers, in terms of mutational burden and imprints. This indicates a clear parallel between the formation of the human placenta and the development of cancer.
Moreover, the team used phylogenetic analyses to retrace the evolution of cell lineages from the first cell division of the fertilised egg. Here, they found evidence to support the theory that the placenta tolerates major genetic aberrations, specifically copy number changes. For example, in one biopsy, each cell had three chromosome tens.
Professor Gordon Smith, a senior author of the study from the University of Cambridge, expressed:
“It was fascinating to observe how such a serious genetic flaw as a chromosomal copy number error was ironed out by the baby but not by the placenta. This error would have been present in the fertilised egg. Yet derivative cell populations, and most importantly those that went on to form the child, had the correct number of copies of chromosome 10, whereas parts of the placenta failed to make this correction. The placenta also provided a clue that the baby had inherited both copies of the chromosome from one parent, which can itself be associated with problems.”
These findings emphasise the need for further studies, using larger samples sizes, to help uncover the cause of complications and diseases that arise during pregnancy.
Image credit: By Jacek_Sopotnicki – canva.com
