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In mammals, there is a strange organ. During its entire growth process, it needs to consume a lot of resources and energy, but it does not accompany the life of the subject of life. Take humans as an example. After it has grown and developed for about 10 months, it will be thrown away. This organ is the placenta.
The placenta is a strange biological phenomenon. For decades, biologists have been puzzled by the obvious waste phenomenon in the placenta: why natural selection allows mammals to exist in their lives A resource-intensive feature that seems so inefficient but crucial?
Now, researchers at the Wellcome Sanger Institute at the University of Cambridge have studied the genome structure of the human placenta, delineating the clearest genome of the placenta so far. They found that the genome of the human placenta is different from any other human tissue. The results of the study were published in the March issue of “Nature”.
One of the corresponding authors of the paper is geneticist Sam Behjati. In 2008, Behjati was still a resident. One day when he was in the maternity ward of the hospital for routine rounds, something puzzled him-in a ward, he saw a mother full of joy. He was holding a perfectly healthy newborn baby in his arms, and his puzzlement stems from the fact that just a few months ago, the doctors found the fetus in the abdomen by analyzing her placental samples during the routine prenatal check-ups on this mother. There are extra copies of chromosome 13.
This kind of chromosome copy number error is usually fatal to newborns. After the postpartum examination of the newborn, the results showed that all 23 pairs of chromosomes were normal. This confuses Behjati, how did this happen? It is important to know that the placenta and the fetus are derived from the same fertilized egg.In the first few days, the fertilized egg implants in the wall of the uterus and begins to divide from one cell into multiple cells. The cells differentiate into various types of cells, some of which form a placenta.
In fact, as early as decades ago, scientists have noticed the genomic mismatch between the placenta and the fetus. Scientists have always estimated that this happens in only 1% to 2% of pregnancies. The new research results show that it is a routine phenomenon that the human placenta is composed of different genotypes, and this strange heterogeneity may protect the fetus from genetic defects.
Researchers performed whole-genome sequencing on 86 samples of 42 placentas, which were taken from different parts of each placenta. They found that every biopsy is a completely different “clonal expansion” of genes (a cell group evolved from a single common ancestor) , each placenta is organized by these large clones adjacent to each other, just like many different tumors together form the placenta.
Not only that, they also found that the genes of each group of cells are completely different, and they are full of genetic abnormalities that only occur in malignant childhood cancers, such as neuroblastoma and rhabdomyosarcoma. These mutations are in the placenta. The number is even higher than in the cancer itself. Compared with other healthy human tissues, the rate of genetic mutations is also incredibly high.
By comparing mutation patterns in placental samples and corresponding umbilical cord samples, the researchers traced the time and location of the origin of placental cells. It turned out that the time for the cells to divide into the fetus and placenta was earlier than expected. In some cases, it even occurs during the first few cell divisions of the fertilized egg. This shows that in the first trimester, the path of placenta development is different from that of the fetus.
Researchers believe that in the first few weeks, when there is a genetic defect that may cause pregnancy problems, the placenta may become a “junkyard” where abnormal genes are piled up. That is to say, in the early stages of development, when some dividing cells randomly produce abnormalities, they may be marked as placenta instead of fetus.
In the experiment, the researchers found evidence that can support the placenta can tolerate genetic defects. In a biopsy, they observed placental cells with three copies of chromosome 10, two of which came from the mother and oneBoth were from the father; but in other or tissues of the same placenta and other cells of the fetus, they only found two copies of chromosome 10 from the mother.
In any other tissue, a chromosome copy number error like this can be a major genetic defect. This error may start in the fertilized egg. The placenta has always carried these early mutations. It is like a genetic defect file established from the first day of pregnancy. Some parts of the placenta have not been corrected, but the fetus itself But it was not hurt by these early mutations.
In addition, these mutations are not a threat to the placenta, because it is not an organ that needs to survive for decades. Because the placenta has a short lifespan, it may not have the same genetic control as other human cells. Behjati believes that another possible explanation for the presence of these mutations in the placenta is that during the first 16 weeks of human pregnancy, the placenta must grow faster than the fetus. Therefore, it may be worthwhile to accumulate mutations as the placenta expands in the uterus. This way it can grow fast and die early.
The new results provide a clear theoretical basis for studying the relationship between genetic variation and delivery results, and help scientists and medical workers better understand issues such as premature birth and stillbirth. Not only that, the new findings also revealed some secrets related to the placenta itself, and revealed some potential connections with cancer.
In fact, scientists have long noticed the similarities between cancer and placenta, such as their avoidance of the immune system, their invasion strategy, and a series of chemical markers on their cell DNA, which guide their genes activity. And they behave similarly to cancer cells. In order to get pregnant, the placenta must invade the mother’s endometrium, enter the mother’s blood supply, and create its own blood vessel network-this is exactly what all cancer cells do. These similarities may bring new ideas to scientists studying cancer.
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