New Genomic Study of Placenta Finds Deep Links to Cancer

I got excited when I read this article. The research seems to be the start of something that could have a lot of applications and implications for pregnancies and cancer treatment and understanding placental and embryonic development. And it’s just fascinating since I’m pregnant.

I wondered what biologists here thought.

The study painted the clearest picture yet of the genomic landscape of the placenta — and it’s unlike that of any other human tissue ever seen by Behjati, who calls it the “wild west of the human genome.” When they sequenced the DNA of 86 samples from 37 placentas, each set of cells was found to be genetically distinct and chock-full of genetic aberrations typically seen only in aggressive childhood cancers.

But during those crucial first weeks, when a single genetic defect could derail the pregnancy, the placenta may also act as a “dumping ground” for aberrations. During early development, when some of the dividing cells randomly develop genetic abnormalities, they might get earmarked for the placenta instead of the fetus, Behjati reasoned. His team found evidence for this theory: In one of the biopsies, the researchers observed placental cells with three copies of chromosome 10 — two from the mother and one from the father. But cells in the rest of the placenta and fetus had two copies of the chromosome (both from the mother), which suggested that the error started in the fertilized egg but was later corrected.

Patches of the placenta continue to carry on these early mutations — a living archive of genetic defects from the first days of pregnancy — while the fetus remains unharmed. But that’s no problem for the placenta, Wildman hypothesizes, because “it’s not constrained by the necessity to successfully produce an organ that’s going to live for 85 years.” The placenta may not have the same genetic checks and balances that other human cells do because of its inherent transience, he said.

Another possible explanation for these mutations, Behjati said, is that the placenta must outpace the growth of the fetus for the first 16 weeks of human pregnancy, so it may be worth racking up mutations as it balloons inside the uterus. It can “live fast and die young,” as Behjati put it.

Wendy Robinson, a medical geneticist at the University of British Columbia who studies early human development, said that it’s an interesting theory, but she disagreed with the notion that the placenta is merely the genetic garbage pail for the fetus. “There’s very rapid cell divisions that occur early in pregnancy, and that probably imposes a strong selection against cells that just can’t keep up, and so only the good cells will contribute [to the fetus],” she said. “So, it’s not that you’re shunting the bad cells to the placenta — and I know it’s semantics — but it’s that you’re selecting for the good cells in the baby and leaving everything else behind.”

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This deserves a “Wow!”

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I know. I’m pretty impressed with God for setting it up this way. But that’s my worldview :slight_smile: But amazing the science just went from - placenta genetic abnormalities are an anomaly to “this probably happens in all pregancies.” Very cool that we can have healthy babies.

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No argument there - It’s impressive from any worldview.

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Why wouldn’t God have just set things up so that there would be no aneuploidies to begin with?

Fixing things later diminishes God, making him seem more of a repairman than a creator.

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20140530-063353-23633853

Valerie may be too young to appreciate the joke … :wink:

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Uh, he did John. What kind of YEC do you think I am? :wink:

I guess since I’m also a Calvinist I suppose it makes sense God would have a merciful plan prepared so even though our bodies undergo errors and death we can still have children and Jesus could be born.

What could conceivably be a mechanism for such an “earmarking” process?

No, He didn’t. If He had, there would be no need for these mechanisms.

No, not everyone can. What’s the spontaneous abortion rate?

It sounds to me like you don’t like how God works in your own worldview. That was weird about your question. If so, I don’t really understand how your faith works. Not that I have to.

Of course not. Btw, you’re allowed not to pick apart every single thing I say to find something wrong with it. I believe I’ve read the rate is 25%, maybe it’s higher than that. It would obviously be much higher without this system or we’d have more children with chromosomal abnormalities and obviously selection is going to kick in. That’s what I meant.

God doesn’t tinker in my worldview.

I think that you focus on worldviews because you don’t want to look at evidence.

I find that your claim diminishes God as a tinkerer.

Since you mentioned it, my faith does not require my ignoring science.

But I am doing so when you don’t make sense, which is most of the time when you try to put anything down to your “worldview,” which seems to be defined in your case as “position I took without any careful consideration to maintain my all-important tribal identity.”

It’s higher, and what you wrote is not even close to your revision.

Beats me. I’m just impressed about findings that allow the question to be asked. Whether or not such an earmarking process exists, we stand to learn something new. How cool is that? :smiley:

I think we probably have several good developmental/cellular mechanisms to consider here. Wendy Robinson points to perhaps the most obvious one IMO: like all occurrences of selection, this one tempts human minds to assume that there was some “earmarking” or “shunting” toward Y when the process was more mundane (things were selected for X and everything else went to Y).

I would suggest that we consider the many reasonably well-known cellular mechanisms that act during any asymmetric cell division. The one that came to my mind is below.

https://www.cell.com/cell/fulltext/S0092-8674(09)01617-1

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I wish I could understand this. The original paper mentioned bottlenecks but I didn’t quite understand how that explained anything, or why there would be bottlenecks. But it’s probably hopeless for me with very little understanding of biology to figure out there mechanisms work.

@Mercer is referring to the spontaneous abortion rate in humans. It’s estimated to be higher than 60%, indeed about 70%. Almost half of pregnancy failures occur before implantation and a similarly large number occur during early gestation (before first missed menstruation). Whether this is a “high” number, biologically speaking, is an interesting evolutionary question that I haven’t explored in depth.

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Sorry about that. Let me try to explain why the 2010 Cell paper represents one kind of biological knowledge that we might use to understand how “damaged” cells could be “earmarked.” The background to that paper is a series of discoveries about cellular aging that showed that cells have mechanisms for collecting globs of damaged or otherwise toxic/worthless proteins and keeping the globs separate from the rest of the cell. This is already very interesting IMO but the really big news was that cells undergoing division could send the trash bags to one cell and keep the other cell safe and clean. This is called spatial quality control, or SQC, and even some bacteria do it.

The 2010 Cell paper describes the systems used by yeast cells to accomplish SQC, and the outline is that the daughter cell that has somehow become the “designated survivor” (I made that up but it seems apt) can arrange for the bags of trash to all end up in the other cell. The result is that cell division is asymmetric to a significant and important extent. Here’s the last sentence of the introduction to the paper:

…provides the daughter cells with the means of clearing themselves of protein damage by a retrograde flow of aggregates into the progenitor cell, which effectively acts as a waste-disposal cell.

The point is that asymmetric cell division is common throughout the tree of life and is used in many cases to allow one cell to offload damage or garbage onto its “sibling” or “mother” cell. The context of the OP, about genetic damage (aneuploidy), is different but the mechanism described by Dr. Robinson seems conceptually the same to me.

Does that help?

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I still can’t imagine how there could be a mechanism for this. Wouldn’t it require some mechanism for karyotyping cells, picking the ones for the embryo that match some template? Any such mechanism would, it seems to me, would be very complicated and very visible.

The same problem applies to

What is this mysterious aneuploidy correction mechanism? Is there any known case of a human having two copies of one parent’s chromosome and none of the other?

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Really appreciate that explanation of the paper. Very interesting!

If you had a different “worldview,” you could just put God down for it. Problem solved!

I don’t think so. Plain ol’ selection could suffice, because aneuploidy throws so much out of balance. That appears to be the case even in cultured fibroblasts with what AFAIK is the most viable (at the whole-organism level) human trisomy:

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I don’t understand that explanation. Are you suggesting that the sample is biased because aneuploid embryos don’t make it to the stage at which they can be sampled? What we have here is, apparently, aneuploid fetal cells in the placenta but normal fetal cells in the embryo. How does selection account for that?