The placenta, like the embryo, arises from the fertilized egg cell, but in contrast to the developing child, it often has a large number of gene mutations. This is shown by new genetic analyzes. According to this, the structure of the placenta is different from any other healthy human organ and in many ways more similar to that of tumors. Further studies could show to what extent mutations in the placenta can influence complications in pregnancy.
Shortly after the fertilized egg has implanted in the lining of the uterus, it begins to divide. The cells multiply and differentiate. One part of the cells forms the embryo, another part creates the placenta, which grows into the maternal tissue and supplies the embryo with nutrients, removes waste products and regulates hormones. The placenta cells behave like a tumor: They penetrate foreign tissue, multiply rapidly and ensure that new blood vessels are formed.
Placenta tolerates genetic abnormalities
A team led by Tim Coorens from the Wellcome Sanger Institute in Hinxton has now shown that the placenta shares many genetic characteristics with tumors. “The rates and patterns of genetic mutations in the placenta are incredibly high compared to other healthy human tissues,” says co-author Stephen Charnock-Jones from the University of Cambridge. If such genetic deviations were to occur in the embryo, the child would in many cases not be viable. In the placenta, however, these abnormalities seem to be the rule rather than the exception.
Coorens and colleagues examined various tissue samples from 42 placentas, taking the samples from different parts of the organ. 86 samples came from biopsies, 106 from microdissections, in which individual cells are removed. For each of these samples, they sequenced the entire genome. “It is noteworthy that 41 of 86 biopsy samples contained at least one change in the number of gene copies,” the researchers report. Such changes would be very problematic in other tissues. The placenta, on the other hand, seemed to tolerate them without any health effects. “As far as we can see from our limited sample, the mutation load in the placenta was not related to whether the pregnancy was problem-free or complicated.”
Trisomy 10 only in the placenta
Among other things, the researchers found a trisomy of chromosome ten in one placenta. Instead of having one copy from the father and one from the mother, as is normal, the placenta cells examined contained two maternal and one paternal copies of this chromosome. “This defect must already have been present in the fertilized egg,” says co-author Gordon Smith of the University of Cambridge. Embryos with such a genetic defect usually die in the womb. But in the case examined, the child was not affected. During the first divisions of the egg, individual cells appeared that did not have the fatal defect. “The cell populations that made up the child had the correct number of copies of chromosome ten,” says Smith. “It was fascinating to see how a genetic defect as serious as a chromosomal copy number error was ironed out by the baby, but not by the placenta.”
Although placenta and embryo arise from the same fertilized egg cell, they can differ in a genetically relevant manner. The researchers even found major differences within the placenta: each tissue sample had a unique genetic signature, and the cells evidently emerged from a single predecessor cell through massive multiplication. This mechanism is known as clonal expansion and is also known from cancer cells. “This suggests that the placenta is a patchwork of mosaic-like, independent genetic units,” the authors say. Among other things, the researchers identified several mutations that also occur in childhood cancer.
“The placenta is something like the ‘wild west’ of the human genome and its structure is completely different from any other healthy human tissue,” summarizes Cooren’s colleague Sam Behjati. “It helps us to protect ourselves from errors in our genetic code, but there is also a high burden of disease associated with the placenta.” Future studies with larger samples could show to what extent genetic defects in the placenta affect the course of pregnancy and how they affect the health of both mother and child.
Source: Tim Coorens (Wellcome Sanger Institute, Hinxton, UK) et al., Nature, doi: 10.1038 / s41586-021-03345-1