The border zone or transition zone or “ Umlagerungszone” marks the division between the fetal and maternal tissues. As might be expected it is not a sharp line, for it is in truth the fighting line where the conflict between the maternal cells and the invading trophoderm takes place, and it is strewn with such of the dead on both sides as have not already been carried off the field or otherwise disposed of. In the earlier stages there is even more evidence of the deadly nature of the conflict than in the later stages.
Johnstone, R. W. (1914). Contribution to the Study of the Early Human Ovum, page 258.
The placenta appears to be a ruthless parasitic organ existing solely for the maintenance and protection of the fetus, perhaps too often to the disregard of the maternal organism.
Ernest W. Page. (1939). The relation between hydatid moles, relative ischemia of the gravid uterus, and the placental origin of eclampsia
The placenta is simply a neuroendocrine parasite.
P. J. Lowry (2008).
Today we take a long, hard look at the human placenta, find out how it is similar to a parasite, a tumor, and a battlefield between the mother and the fetus, and how this makes pregnancy much more risky than it could have been.
To start our journey, think about this question: why is pregnancy so dangerous? The reason is that, in a pregnancy, there are two bodies, instead of one, and they have different interests. They cooperate, but they also fight each other.
The fetus is selfish: it wants itself to be strong. The mother is also selfish: it would rather not devote too much energy to the fetus, because if it does, it would not have enough energy to make another fetus. This is the secret war, taking place on the placenta.
Unless otherwise noted, I'm generally referring to Haig, David, ‘Genetic Conflicts in Human Pregnancy’, (1993).
The ignored placenta
The placenta... the place where the embryo meets the mother, where the embryo receives the nutrients and the mother receives the waste products. It is a vital organ, but rarely given a thought at all. Think about all the vital organs: brain, heart, lung, stomach, guts, liver, skin, muscles, bones, hand, arm, feet, leg, ovary... each having its own rich implications in culture.- "Screaming at the top of the lungs"
- "Brain of the team"
- "Right to bear arms"
- "Got guts"
- "Don't drink too much or your liver would complain"
- ...
But what about the ignored organs? The pancreas is all but forgotten, and we can't really blame that. It's small, and has been dismissed as merely a meaty cushion until about 19th century. Even now, its only claim to fame is that it makes insulin, which keeps us from becoming diabetic.
The kidneys are also ignored, and I don't know why, since everyone knows how vital the kidneys are, for making pee.
Which brings me to the placenta. The main organs associated with sexual reproduction are ovary, uterus, vagina, penis, testicle, and the placenta. Except the placenta, they are all deeply meaningful in pop culture.
I suspect this ignorance is due to the temporary and ambiguous nature of the placenta. It doesn't seem to belong to the baby or the mother, and is immediately thrown away after birth. There are no placental chronic diseases. You can't get "chronic inflammation in the placenta". What I'm trying to show is that the placenta slips through the cracks of our conception of body parts. It doesn't fit any of the boxes, and as such, it just falls outside the boxes, outside our minds.
About the only time the placenta gets into the public eye is when it is being used in deviant ways that cross the boundaries that according to the culture should not be crossed. For example, the placenta is a piece of human meat, therefore eating it is cannibalism, which is bad. As another example, the placenta is supposed to be medical waste, therefore keeping it attached to the baby (lotus birth) is impure (it is also medically dangerous). Other than cremation as garbage, burial seems to be the only accepted way to interact with a placenta in Western culture.
As a side note, the ancient Egyptians took great interest in the placenta, considering it as a "second soul" (Images of the human placenta, Roberto Romero). The illustration below shows an ancient Egyptian carving containing a placenta with a dangling umbilical cord. The placenta-carrier is clean-shaven, unlike the other carriers, who were bearded. This marks him as very special.
The king wears the red crown of Lower Egypt, while holding a mace head and the flail sign of authority. The king is preceded by his vizier carries two inkpots used for writing. Before the vizier are four persons carrying royal standards. Two of them have the falcon Horus, the third has the form of the jackal god (local god of Asyut) and the fourth has the representation of the royal placenta. In front of the bearers, there are two rows of enemies with cut head which is placed between their legs.This interpretation came from (Seligmann, Murray, 1911). Note upon an early Egyptian standard. Man. Vol 11. Royal Anthropological Society of Great Britain and Ireland, London, pp 165-171.
 |
| Source |
That is enough cultural background. Let's look at some placentas.
What is the placenta?
After an egg and a sperm fuse to create a zygote, the zygote clones itself into several dozens of cells. The inner part develops into the embryo. The outer part, called the trophoblast, has two jobs. One: it develops into a soft protective bubble around the embryo. Two: it must invade the endometrium, the surface of the mother's uterus.
 |
| Source |
This blob of cells lands softly on the endometrium, and the trophoblast invasion starts. Tendrils of cells penetrate deeply into endometrium territory, while the maternal cells resist. The two sides fight to a stalemate, and the second phase begins. The tendrils of cells secrete proteolytic enzymes, chemicals that break down proteins. This dissolves the endometrium around the fingers, leaving behind a vast cavern, filled with blood, divided into valleys by walls of entometrium tissue.
The vast cavern is topped by the placenta, and bottomed by the lower level of the endometrium. Arteries and veins from the mother dot the floor of the cavern, keeping the blood fresh. Little trees hang down from the placenta, with little fetal blood vessels inside, releasing waste into and taking nutrients from the valleys of blood.
This cavern is in fact like an inverted lung. In the lung, the tree branches contain the lake of air, and the blood vessels outside the trees exchange with the lake of air. In the placenta, the tree branches contain the blood vessels, and the lake of blood is outside the trees.
 |
| Source |
 |
| Placenta illustrated. |
You can easily tell apart the two sides of the placenta: the maternal side of the placenta is bumpy, covered with little trees, while the fetal side is smooth and veiny.
A metaphor for pregnancy as seen by selfish genes
Each selfish gene is a little person. Each human is a company. A gene can be present in multiple humans, just like a person can hold stocks in multiple companies.
Now consider this situation: a woman mated with a man, and now there is a fetus growing in the woman's uterus. The man has gone away, so there are only two humans in the situation: the woman and the fetus.
There are three kinds of genes:
For each kind, we can consider how much stocks they hold in each company.
Now consider this situation: a woman mated with a man, and now there is a fetus growing in the woman's uterus. The man has gone away, so there are only two humans in the situation: the woman and the fetus.
There are three kinds of genes:
- Those that are in the mother, but not the fetus.
- Those that are in the mother and the fetus.
- Those that are in the father and the fetus.
For each kind, we can consider how much stocks they hold in each company.
- 100% in the mother, 0% in the fetus.
- 50% in the mother, 50% in the fetus.
- 0% in the mother, 100% in the fetus.
It is then obvious that there is a conflict of interest. The genes with a large share in the fetus would want the mother to lavish all the energy on the fetus, while those with a large share in the mother would rather conserve some energy for future babies.
And thus, we have two wars at the same time:
- A mother-fetus war, where the genes in the mother and genes in the fetus struggle over how much energy to dedicate to the fetus.
- A father-mother war within the fetus. The genes from the father want all the energy for the fetus, while the genes from the mother struggle for moderation.
We will see how the human placenta is shaped by these two wars.
The placenta is very diverse
Conflict is the root of creativity. Humans are the most ingenious when they are trying to one-up each other, in war, business, art, or friendly competitions. Similarly, evolution is most creative at the sites of eternal war. The war between the predator and the prey gave rise to the many kinds of eyes, jaws, legs, fins, brains, and a thousand other traits. Sexual selection gave the diverse courtship rituals, displays, genitalia, and other stuffs.
What is less known is the mother-fetus conflict, which gives rise to the diversity of the placenta. From (Haig, 1993)
Mossman (1937) has remarked that the placenta is probably more variable in structure than any other mammalian organ, and Rothchild (1981) has contrasted the highly variable regulation of the postovulatory follicle (when maternal and fetal genes are vying for control) with the relatively uniform regulation of the preovulatory follicle.This very specific diversity, postovulatory, is strong evidence that the diversity is specifically evolved as a result of mother-fetus conflict, as the mother's body braces itself after ovulation (where the egg cell is released) for the battle with the fertilized egg.
The fetus as a foreign invader, a pathogen
Since the fetus wants more from the mother than the mother is willing to give, there is bound to be conflict, which is concentrated on the placenta, the organ with which the fetus makes contact with the mother. Reading the description of how placenta is grown reminds one of an alien invasion of earth. The fetus cells strike deep within the uterus walls, melts down its surface, leaving behind a lake of blood to suck nutrients from.
In the eyes of the mother's immune system, the fetus is an invader. Organ transplants sometimes fail, and when they do, it's most likely because the immune system considers it as a foreign invader to be destroyed. The fetus is basically a giant foreign organ, so why doesn't the mother's immune system destroy it? Why doesn't the placenta, a giant leech on an open wound on the mother's uterine wall, cause a massive inflammation?
The answer is simple: the placenta releases chemicals into the maternal blood to suppress the immune system, and at the same time, it blocks all immune cells from the mother from entering the fetus. It is essentially a great firewall for the fetus.
The result is that the fetus, with placenta included, becomes an immunologically privileged site. The mother's immune system leaves it alone. Not only that, the mother's immune system becomes weakened in general.
Finally, the invasion of the fetus cells has long-term consequences. The invading cells from the fetus can get into the bloodstream of the mother and be carried all over her body, and settle down, make a home, forever. This is called microchimerism. It reminds me of cancer metastasis. Some research suggests that such fetal cells in the mother's body can cause autoimmune diseases, which can be lessened by having another pregnancy, which suppresses the immune system again. If you are a bit cynical, you could say that the fetus created a problem that only it could solve.
Such left-behind cells can even develop into choriocarcinomas (placenta cancer), many years after the woman's last pregnancy.
From Review of Y.W. Loke, Life’s Vital Link: The Astonishing Role of the Placenta:
... women with rheumatoid arthritis have significant improvement of their symptoms when they are pregnant, presumably because of these anti-inflammatory signals produced by the placenta. Interestingly, rheumatoid arthritis itself may be caused by fetal cells that cross the placenta during pregnancy. While traditionally described as an autoimmune disease, it is possible that rheumatoid arthritis and other autoimmune disorders like lupus are actually caused by alloimmune responses to fetal cells that escape the placenta and take up residence in the mother. In support of this idea, autoimmune diseases are found more frequently in older adult women than men.
The placenta is like an invasive cancer
Similarities between trophoblast and malignant cells have been noted for more than a century. Shared features include rapid proliferation, invasion of neighbouring tissues, deportation to distant sites, vasculogenic mimicry, induction of angiogenesis and modulation of immune responses.
Trophoblast is selected to evade maternal restraints on its invasion of maternal tissues, with each new maternal restraint undermined by new trophoblastic countermeasures. By this evolutionary process, trophoblast has evolved abilities to degrade extracellular matrix, penetrate basement membranes, induce apoptosis in maternal immune cells and ignore apoptotic signals. All these attributes evolved because of the benefits they provided fetal genes in their struggle with maternal genes over the control of maternal physiology during pregnancy but all can be redeployed by tumour cells in intrasomatic selection to evade ‘host’ defences and facilitate malignant spread.
Pregnancy outside the uterus
Ever heard of "ectopic pregnancy"? It means "pregnancy outside the womb". It's surprising, but it's actually possible for the fetus to develop healthily in the fallopian tube, or even in the abdomen. Incidentally, it means that man can get pregnant. Except you should note that ectopic pregnancies are very dangerous for the host.
An embryo’s ability to implant and develop to term at an extrauterine site provides some of the clearest evidence for the absence of intimate ‘maternal–fetal dialogue’. Neither mother nor embryo benefits from ectopic implantation but embryos have evolved to ‘ignore’ most maternal advice as potentially self-interested.We can learn two things:
- The placenta is the most important organ for the development of the fetus. The uterus is not at all necessary.
- The mother-fetus conflict has desensitized both sides from the desperate shouting of the other, sometimes with tragic outcomes.
The tug-of-war over blood supply, sometimes with lethal results
Of all pregnancy-related maternal deaths, 14% are caused by high blood pressure caused by pregnancy. But how?Remember, due to the mother-fetus conflict, the fetus wants more nutrients from the mother than the mother is willing to give, as such, there is a battle over how much nutrient flows through the lake of blood. The fetus wants more blood flow, higher blood pressure, with more glucose in it, and the mother pushes back.
One curious fact is that in a pregnant woman's blood, both hormones for increasing and decreasing blood pressure are increased. This is a clear sign of the tug-of-war.
There is currently no consensus about what determines maternal blood pressure during pregnancy, but the simultaneous elevation of vasoconstrictors (Baker et al., 1990) and vasodilators (Cusson et al., 1985; Milsom et al., 1988) is suggestive of conflict.To return to our metaphor, this is like the stockholders in the FetalCorp sending increasingly stronger letters begging for money from the MotherCorp, and stockholders in the MotherCorp increasingly becoming numb to those letters.
- "We are running out of cash, please send $1000"
- "Okay we will send $100."
- "Seriously, we need $2000 right now or we will go bankrupt."
- "Nah you pulled that trick last time. You just keep inflating the numbers trying to get more money than you need, $150 is all you'll get this week."
This escalation of shouting-and-ignoring takes place over the evolution of humans, with both the fetus and the mother tugging harder on their end.
The mother-fetus war over blood sugar can lead to diabetes
This section is based on Gestational Diabetes and Maternal Fetal Conflict (2016).
I mean, sugar is tasty and nutritious, and the only source of nutrition for a growing fetus is the sugar in the mother's blood, flowing under the placenta. Thus, the fetus would try to increase the blood sugar level, while the mother's body would fight back. When the fetus wins a bit too much, the mother would suffer from "gestational diabetes". Up to 10% of pregnancies develop it.
This is mainly caused by two things:
- Placental hormones that block the ability of the maternal body to utilize insulin (conferring insulin resistance);
- The placenta contains enzymes for rapid insulin degradation.
Finally,
late in pregnancy maternal insulin action is 50–70 % lower than in nonpregnant controls. This demonstrates a reduced efficacy of insulin in reducing glucose in the maternal blood stream, thereby increasing the amount of time glucose is available to the developing fetus.
The spectre of pre-eclampsia
Pre-eclampsia is essentially a symptom of high blood pressure that appears in about 2-8% of pregnancies. It causes around 15% of pregnancy deaths, and seems to only appear in humans. That's right, yet another thing that's uniquely human! A new and exciting way for mothers to die!Its cause is unclear, but there are strong evidences that it is, in essence, the result of desperate attempts by the placenta to save the fetus. From Maternal-fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer (2015):
Pre-eclamptic placentas release factors into maternal blood that cause endothelial damage (maternal pathology) possibly as an adaptation of insufficiently nourished fetuses to increase blood flow to the placenta (fetal physiology). But maternal feedback to limit damage cannot be ‘trusted’ because mothers and offspring have incentives to misrepresent their true state.Basically, if the fetus didn't get enough nutrients during the development, usually because the placenta isn't attached well, it would force the mother's blood pressure to rise in a desperate bid for life. This can then lead to pre-eclampsia, which can deteriorate as placenta cells die, peel off, and gets carried by the blood into multiple locations in the mother's body, causing inflammation (since those clumps of cells are aliens to the mother's immune system).
The tragic end of pre-eclampsia is the death of both the fetus and the mother.
The inhuman past of the placenta
Not only from parasites, many genes of the placenta came from viruses. From Retroviruses and the Placenta (2012):
Retroviruses are often expressed in the placenta. Placental expression probably evolved to facilitate retroviral transmission from mother to offspring and from offspring to mother. In the process, the placenta became a site where retroviral genes were ‘domesticated’ to serve adaptive functions in the host, including the manipulation of maternal physiology for the benefit of the fetus.Retroviruses are just viruses that can write themselves into your DNA, so that they can get copied alongside normal DNA, ready to "wake up" and start producing copies of the virus at a later time. Our DNA is full decaying code from the ancient retroviruses, some of which has been "domesticated" and converted for our own use, while others have been abandoned and ruined with time.
This really shouldn't be a surprise, considering all the comparisons we have made between the placenta, the parasites, and the tumor, all creatures that must make a living in a hostile country.
The mother-father war
We have seen how the genes in the mother and the fetus can compete, with sometimes tragic consequences. However, the war does not stop there. There is a war within the fetus, too, between genes from the mother and those from the father.
It is not a well-known fact, but some genes in a fertilized egg "know" if they came from the father or the mother. This is called "genomic imprinting".
Within a fetus, the father's genes would be greedier, because even if the fetus eats some much energy from the mother that the mother can't raise another child, the father can just find another mother and propagate his genes again. The mother's genes would be more moderate, since even if this fetus end up small and sickly, the mother can have another child. As a result, there is another tug-of-war right inside the fetus.
This tug-of-war lasts well outside the womb, into childhood. In general, maternal genes want the child to live independently faster, and be less of a burden to the mother. Paternal genes are the opposite. For a review, see The tempo of human childhood: a maternal foot on the accelerator, a paternal foot on the brake (2018)
Normally, the two sides fight to a standstill in the middle, but sometimes the fertilization goes south, and this delicate balance tumbles into chaos, like a tug-of-war with only one side.
The following refers to Maternal-fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer (2015), and Hydatidiform mole and triploidy: the role of genomic imprinting in placental development (2005).
Too many father's genes (diandric pregnancy)
If the zygote somehow gets fertilized by two sperms, and loses the mother's gene, it would have two copies of the father's genes and none of the mother's genes. This would result in molar pregnancy, where the zygote develops into a voracious placenta without an embryo. It is like a hungry mouth that feeds, without a body for the food to go into.
The phrase "molar pregnancy" describes the shape of the resulting placenta: it is molar, meaning that it has a bumpy surface, as if it has moles.
The prevalence is 1 in 1500 pregnancies (Molar and nonmolar triploidy: Recurrence or bad luck, 2020). Further, if you've had a molar pregnancy, the next time you get pregnant, the probability of another molar pregnancy shoots up to 1 in 100.
In 2 to 3% of cases, a molar pregnancy develops into choriocarcinoma, which is a malignant, rapidly growing, and metastatic (spreading) form of cancer.
In more benign cases (diandric triploidy), the fetus has 2 copies of the father's genes, and 1 copy of the mother's genes (diandric triploidy). The fetus will still develop, with a large, invasive placenta. The fetus will never become viable, however.
The lesson here is that in every fetus there is a cancerous nature, usually under control by the maternal genes, but can be unleashed when the maternal control is gone.
Too many mother's genes (digynic pregnancy)
In the opposite situation, the fetus would be too meek and humble, demanding too little for itself. I cannot find any report on 2 copies of the mother's genes, with no father's genes (digynic diploidy), except a guess in (A Genetic Review of Complete and Partial Hydatidiform Moles and Nonmolar Triploidy, 1992), where the authors speculate that digynic diploidy results in some benign ovary tumors.
There are plenty of reports on fetus with 2 copies of the mother's genes, and 1 copy of the father's genes (digynic triploidy). In such cases, the fetus usually has a big head, small body, and a small, non-molar placenta.
In any case, such triploid fetus cannot survive for long. Most were aborted in the first trimester, and the longest survival reported was a digynic triploid baby, dying at 10.5 months.
Although most triploid conceptions end in first trimester spontaneous abortions, there are few reports of live born infants with triploidy, with the longest reported survival of digynic triploidy at 10 ½ months. Based on personal communication of the authors of same report, about half of previously reported 38 triploidy cases were live-born and lived for a few minutes to 5 days.
Bonus: A few fun facts about the placenta
From The Placenta in Lore and Legend (1963).
Placenta is a sibling of the child that plays with the child in sleep. Too wholesome.
People living in Achinsk, Siberia, have similar beliefs and hold that the placenta is a girl's sister or a boy's brother. Sickness of the infant denotes that the buried placenta is ill, and the grave is therefore treated with medicaments or the placenta reburied in a more "comfortable" site. The soul of the placenta can leave to play with the child, an event they believe to have taken place when the child laughs in its sleep.Fun fact about Icelandic: fylgia both means "placenta" and "guardian angel".
The placenta was believed to have supernatural properties as oppose(d to merely physical relationship to the newborn. These properties appear in their simplest form in certain beliefs held by the Icelanders, who imagine that the child's guardian spirit or part of its soul resides in the placenta -- hence its name "fylgia," meaning "guardian angel." The placenta must not be thrown under the open sky lest demons get it and work the child harm, nor must the placenta be burned; otherwise the child would have no guardian angel, a situation almost as bad as having no shadow. It is usual to bury the placenta under the floor, so that the mother steps over it as she gets out of bed. If it is thus treated, the child will later have a guardian spirit in the shape of a bear, a wolf, an eagle, an ox, or a wild boar (whichever animal most resembles his disposition).The tradition of burying placenta under a tree appears in many cultures, such as this one:
Swahili of East Africa. After the birth of a child, the placenta and cord are buried in the courtyard and the spot marked. Seven days later the hair of the child is shaved off and placed on the spot together with finger and toenail clippings. A coconut palm is then planted, and the child, as the tree grows, will point to it and say, "This palm tree is my navel."How to destroy the placenta, to avoid it being taken for black magics:
In Norway the mother her- self stabs the placenta with a knife so that a horrible monster would be prevented from taking her life at a later date... The Transylvania gypsies also believed that both placenta and meconium must be burned; otherwise wicked fairies could turn them into vampires who would attack the child.
Big wat
A remarkable custom in the Province of Obolonskii causes the placenta to be tied firmly to the head of the child, who has been washed in the mother's urine as a cure for convulsions. It is also believed that the newborn may be made to breathe by stroking with the placenta.Magic of Chinese medicine!
Chinese women are given dried placenta to hasten labor and have great faith in a draught of boy's urine.Finally, some fun fact from the Bible, I Samuel 25: 29:
Even though someone is pursuing you to take your life, the life of my lord will be bound securely in the bundle of the living by the LORD your God, but the lives of your enemies he will hurl away as from the pocket of a sling.According to the paper, this "bundle" probably refers to the ancient Egyptian tradition of keeping the placenta as a container of soul, with which one can be reborn.
Margaret Murray accumulated considerable evidence that the "bundle of life" refers to the Egyptian custom of wrapping the royal placenta in a sacred bundle with which the king's health and destiny were linked. When the king became old, ritual murder commonly took place. Originally the king himself was killed; later a substitute victim was sacrificed, and the "bundle of life" containing the royal placenta was opened and rewrapped, an act symbolizing the rebirth of the king. A high-ranking official was appointed to perform this ceremony, known as "the Opener of the King's Placenta."
No comments:
Post a Comment