Placenta is 'dumping ground' for defects
Thursday March 11th 2021
The placenta is a “dumping ground” for genetic defects and resembles a “patchwork of tumours”, according to the first high-resolution survey of the genomic architecture of the human placenta.
Writing in the new edition of Nature, scientists from the Wellcome Sanger Institute and the University of Cambridge, UK, say their findings provide new information for those studying the association between genetic aberrations and birth outcomes.
Although it has been known for a long time that the placenta is genetically robust and is different from other human organs, problems with the placenta remain a major cause of harm to the mother and foetus.
For this study, the scientists conducted whole genome sequencing of 86 biopsies and 106 microdissections from 42 placentas, with samples taken from different areas of each organ.
They found each one of the biopsies was a genetically distinct clonal expansion, which indicated a parallel between the formation of the human placenta and the development of a cancer.
Analysis also identified specific patterns of mutation that are commonly found in childhood cancers, such as neuroblastoma and rhabdomyosarcoma, with more of these mutations in the placenta than in the cancers themselves.
Senior study author Professor Steve Charnock-Jones, of the University of Cambridge, said: “Our study confirms for the first time that the placenta is organised differently to every other human organ, and in fact resembles a patchwork of tumours. The rates and patterns of genetic mutations were also incredibly high compared to other healthy human tissues.”
Phylogenetic analysis was used to retrace the evolution of cell lineages from the first cell divisions of the fertilised egg and found evidence to support the theory that the placenta tolerates major genetic flaws.
In one biopsy, the researchers found three copies of chromosome 10 in each cell, two from the mother and one from the father, but other biopsies from the same placenta and from the foetus carried two copies of chromosome 10, both from the mother. A chromosomal copy number error such as this in any other tissue would be a major genetic flaw.
Senior study author Professor Gordon Smith, from the University of Cambridge, said: “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.”
Now that the link between genetic aberrations in the placenta and birth outcomes has been established, further studies using larger sample sizes could help to uncover the causes of complications and diseases that arise during pregnancy.
Coorens THH, Oliver TRW, Sanghvi R et al. Somatic mutations reveal widespread mosaicism and mutagenesis in human placentas. Nature 10 March 2021
Tags: Childbirth and Pregnancy | Genetics | UK News
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