The Uterus: A Natural History

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At only 3 inches long and weighing about 60 grams, the uterus isn’t a flashy, attention-grabbing organ. When it comes to human health, the heart usually comes first, followed by the brain, then perhaps the digestive system. Yet the uterus plays an outsized role. It’s the carrier of all life, the subject of scrutiny in political forums, and a source of delight and despair for sexually mature women. It causes bleeding and pain, allows 211 million women to get pregnant every year, and is partially responsible for the 10 to 20 percent of those pregnancies that end in miscarriage.

Despite its ability to create life, there are dozens of crucial things we have yet to learn about the uterus. At least we’ve abandoned the theory that it travels freely around the body, causing hysteria, and that it can be manipulated by smelling salts.

Today we know the uterus sits low in the abdomen, held in place by muscles and ligaments. It is connected to the vagina by the cervix and receives unfertilized eggs from the ovaries via the fallopian tubes, which are connected to both sides of the uterus. It expands from 3 inches to the size of a watermelon by the end of a pregnancy in order to hold the baby and placenta—and, luckily for new mothers, naturally deflates about six weeks after the child is born.

But how did we develop this organ, how does it operate—or malfunction—in the body, and what's the outlook for the future?

THE EXTRAORDINARY EVOLUTION OF THE MAMMALIAN UTERUS

Until recently, scientists didn’t even understand how mammals evolved uteruses that allowed for live birth. Soft tissue is rarely preserved in the fossil record, which means scientists can study the bone structure of past organisms but are often left guessing when it comes to organs.

Up until marsupial ancestors appeared 220 million years ago, new life came out of eggs. Before that time, even the earliest mammalian predecessors, the group called monotremes (like echidnas and platypuses) were still laying eggs. But by 105 million years ago, placental mammals had evolved elaborate uteruses that allowed for invasive placentas, maternal tolerance of the fetus, and long gestation periods. What caused this evolution? Why did mammals suddenly appear?

In 2015, a team of researchers from the University of Chicago, Yale, and several other universities found a major clue in the hunt to discover the origin of mammals: genetic parasites. Called transposons, these snippets of non-protein-coding DNA regularly changed positions in the genome, an action called “jumping genes.” The leap-frogging transposons caused genes from other tissues—like the brain and digestive system—to be activated in the uterus. As more and more genes were expressed in the uterus, organisms shifted from producing eggs to giving live birth. The shift began sometime between 325 and 220 million years ago with the appearance of monotremes, and continued for hundreds of millions of years until placental mammals appeared, sometime between 176 and 105 million years ago.

During the genetic shift, more than 1000 genes turned on in therians, common ancestors to marsupials and placental mammals (like us). Many of these genes related to maternal-fetal communication, and especially the suppression of the maternal immune system in the uterus so it didn't reject the developing fetus. Because many of the transposons had progesterone binding sites that regulated the process, the uterus evolved to be extremely sensitive to that hormone (which is produced by the ovaries during the release of a mature egg; it prepares the uterine lining to receive a fertilized egg). The study appeared in the journal Cell Reports. In a press statement, Vincent Lynch, one of the study’s authors, said the discovery shed light on how “something completely novel evolves in nature.”

“It’s easy to imagine how evolution can modify an existing thing, but how new things like pregnancy evolve has been much harder to understand,” Lynch continued. “We now have a new mechanistic explanation of this process that we’ve never had before.”

THE MYSTERIES OF MENSTRUATION

While live birth defines mammals, including everything from whales to dogs to bats, there’s one thing that sets humans apart from most other species: menstruation. We’re part of an exclusive club that’s limited to old world primates, elephant shrews, and fruit bats. All other species remodel and reabsorb the endometrium, or uterine lining. So why do humans have to deal with the hassle of a period? Scientists aren’t quite sure. One theory is that the process protects us from abnormal pregnancies. The human gestation period is so long and requires so many biological resources that it’s better to reject all but the best candidates. And the reason we have periods is far from the only thing we don’t understand about menstruation.

“There is so much we don’t know,” says Hilary Critchley, OB/GYN and professor of reproductive sciences at the University of Edinburgh. “Not only why do we have normal periods, but particularly why does a woman have heavier periods?” Critchley and her colleagues published a paper that compiled years’ worth of studies in Human Reproduction Update in July 2015. They found far more questions than answers. Their research confirmed what is known: that a decline in progesterone triggers menstruation, and that the endometrial coagulation system plays a part in stopping the bleeding. But plenty of questions remain about the mechanics of the process.

Doctors don’t know what regulates inflammation during menstruation, what causes the bleeding to stop, or how the uterus repairs itself so quickly without creating any scar tissue. They also don’t understand the causes of diseases associated with menstruation, like polycystic ovary syndrome and endometriosis. Neither currently has a cure, and they afflict around 1 in 10 women. In the most extreme cases of endometriosis, women have no choice but to undergo hysterectomies.

“If you’re in the workforce, period problems can be really embarrassing and really difficult to deal with. This is where I see the unmet need for new treatments,” Critchley tells Mental Floss. “A woman now has 400 periods in a lifetime. A woman (100 years ago) had 40. If you’ve got more periods, you’ve got more opportunity for it to be a problem.” This increase in the number of periods by a factor of 10 in the past 100 years is due to contraception and improved nutrition. The downside is that's a lot more opportunity for menstruation to cause problems.

GROWING AN EXTRA ORGAN TO MAKE A BABY

Menstruation isn’t the only area of female reproductive health that has researchers scratching their heads. Perhaps even more confounding is the placenta, a transient organ created during pregnancy by the embryo.

“I’d say the placenta is probably the least studied and the least understood organ in the body,” says Catherine Spong, acting director of the National Institute of Child and Human Development. She oversees the Human Placenta Project (HPP), which aims to develop new tools to monitor the placenta throughout its development. “If you could understand how the placenta allows two genetically distinct entities not only to grow, but also thrive, the implications for enhancing our understanding of immunology and transplant medicine would be pretty remarkable.”

Stacy Zamudio, a recipient of a grant from the HPP and director of research at Hackensack University Medical Center, calls the placenta “the most wonderful organ ever.” Her research focuses on placenta accreta (when the placenta grows too deeply into the mother’s uterine wall and even outside organs).

“It breathes, it produces hormones, it produces immunologic factors that protect the baby against infection. It acts like a skin, a liver, a kidney, a lung—it does all the functions of the other organs in one organ,” Zamudio says.

graphic explaining the placenta and its importance
Human Placenta Project

The placenta achieves this by hooking into arteries in the uterus, essentially hijacking the mother’s body so the embryo can have a constant stream of nutrients and oxygen as it develops. When it’s functioning normally, the placenta ensures a positive outcome: healthy baby, healthy mother. But when things go wrong with the placenta, they quickly go from bad to worse.

The placenta can be under-invasive, meaning the connection to the mother’s blood isn’t strong enough. The baby stops developing because it’s not getting nutrients, and in the worst cases the mother can suffer from preeclampsia, which causes life-threateningly high blood pressure and can only be treated by immediate delivery of the baby. Or, as with the cases Zamudio studies, the placenta can be over-invasive, infiltrating the uterus and other organs beyond it like a cancer. Finally, in a complication known as placental abruption, the placenta can peel away from the uterus before delivery, removing the baby’s source of oxygen and nutrients and causing heavy bleeding in the mother.

Pregnancy can be a dangerous balancing act, and if doctors had better ways of monitoring the placenta’s development over the course of pregnancy, they might be able to prevent or avert the worst outcomes.

FROM WOMB TRANSPLANTS TO TRICORDERS

In October 2014, a baby born to a Swedish couple became an exciting example of the possible future of maternity—he was the first child ever born of a transplanted uterus. (The first pregnancy from a womb transplant, in Turkey, was terminated in 2013 when the fetus had no heartbeat.) The 36-year-old mother, who was herself born without a uterus, received a donation from a woman in her 60s, and had a frozen embryo successfully implanted in the transplanted organ. Although the child was born prematurely, he and the mother were otherwise healthy after the pregnancy. Since then, four more women who received uterus transplants from doctors at the University of Gothenburg have gotten pregnant.

The pioneering surgery is now spreading across the world. Doctors at Cleveland Clinic performed the first successful uterus transplant in the U.S. just last week. The 9-hour surgery was performed on a 26-year-old patient with uterine factor infertility (an irreversible condition affecting 3 to 5 percent of women that prevents pregnancy). If the patient heals and can become pregnant, the surgery could offer new hope to women who previously thought they were doomed to infertility.

Despite the enormous advances made in the last decades concerning women's health, many questions about the uterus remain unanswered. Scientists don’t know why the placenta sometimes grows too little or too much, or how it communicates with the rest of the organs in the mother’s body. They don’t know why some women have debilitating cramps during their periods that have been likened to the pain of having a heart attack. But with scientists around the globe investing time and resources into such questions, it might not be long before we have real answers and solutions to these problems.

"We're not that far away from the tricorder in Star Trek," Zamudio says, referring to developing technologies like nanomagnetics. "I'm hoping that I'll be alive long enough to see a doctor be able to wave the instrument over the woman's abdomen and tell me what the glucose level is in that body."

‘Water’ in Kansas City Woman’s Ear Turned Out to Be a Venomous Brown Recluse Spider

N-sky/iStock via Getty Images
N-sky/iStock via Getty Images

Susie Torres, a resident of Kansas City, Missouri, woke up on Tuesday morning with the distinct feeling that water was lodged in her left ear. She likened it to the swooshing sensation that can often happen after swimming, WDAF-TV reports.

Instead of waiting for the problem to resolve itself, Torres went to the doctor—a decision that might have saved her from some serious pain. The medical assistant was the first to realize something was alarmingly amiss, and immediately called for backup.

“She ran out and said ‘I’m going to get a couple more people,’” Torres told 41 Action News. “She then said, ‘I think you have an insect in there.’” For many people, the thought of having any live insect stuck in an ear would be enough to cue a small- or large-scale freak-out, but Torres stayed calm.

The doctors “had a few tools and worked their magic and got it out,” Torres said. The “it” in question turned out to be a spider—and not just any harmless house spider (which you shouldn’t kill, by the way). It was a venomous brown recluse spider.

“Gross,” Torres told WDAF-TV. “Why, where, what, and how.”

Miraculously, the spider didn’t bite Torres. If it had, she would’ve ended up visiting the doctor with more than general ear discomfort: Brown recluse bites can cause pain, burning, fever, nausea, and purple or blue discoloration of the surrounding skin, according to Healthline.

Torres may have remained admirably level-headed throughout the ordeal, but that doesn’t mean she’s taking it lightly. “I went and put some cotton balls in my ears last night,” she told WDAF-TV. “I’m shaking off my clothes, and I don’t put my purse on the floor. I’m a little more cautious.”

Is this the first time an insect has posted up in the ear of an unsuspecting, innocent human? Absolutely not—here are six more horror stories, featuring a cockroach, a bed bug, and more.

[h/t WDAF-TV]

12 Fantastic Facts About the Immune System

monkeybusinessimages/iStock via Getty Images
monkeybusinessimages/iStock via Getty Images

If it weren't for our immune system, none of us would live very long. Not only does the immune system protect us from external pathogens like viruses, bacteria, and parasites, but it also battles cells that have mutated due to illnesses, like cancer, within the body. Here are 12 fascinating facts about the immune system.

1. The immune system saves lives.

The immune system is a complex network of tissues and organs that spreads throughout the entire body. In a nutshell, it works like this: A series of "sensors" within the system detects an intruding pathogen, like bacteria or a virus. Then the sensors signal other parts of the system to kill the pathogen and eliminate the infection.

"The immune system is being bombarded by all sorts of microbes all the time," Russell Vance, professor of immunology at University of California, Berkeley and an investigator for the Howard Hughes Medical Institute, tells Mental Floss. "Yet, even though we're not aware of it, it's saving our lives every day, and doing a remarkably good job of it."

2. Before scientists understood the immune system, illness was chalked up to unbalanced humors.

Long before physicians realized how invisible pathogens interacted with the body's system for fighting them off, doctors diagnosed all ills of the body and the mind according to the balance of "four humors": melancholic, phlegmatic, choleric, or sanguine. These criteria, devised by the Greek philosopher Hippocrates, were divided between the four elements, which were linked to bodily fluids (a.k.a. humors): earth (black bile), air (blood), water (phlegm) and fire (yellow bile), which also carried properties of cold, hot, moist, or dry. Through a combination of guesswork and observation, physicians would diagnose patients' humors and prescribe treatment that most likely did little to support the immune system's ability to resist infection.

3. Two men who unraveled the immune system's functions were bitter rivals.

Two scientists who discovered key functions of the immune system, Louis Pasteur and Robert Koch, should have been able to see their work as complementary, but they wound up rivals. Pasteur, a French microbiologist, was famous for his experiments demonstrating the mechanism of vaccines using weakened versions of the microbes. Koch, a German physician, established four essential conditions under which pathogenic bacteria can infect hosts, and used them to identify the Mycobacterium tuberculosis bacterium that causes tuberculosis. Though both helped establish the germ theory of disease—one of the foundations of modern medicine today—Pasteur and Koch's feud may have been aggravated by nationalism, a language barrier, criticisms of each other's work, and possibly a hint of jealousy.

4. Specialized blood cells are the immune system's greatest weapon.

The most powerful weapons in your immune system's arsenal are white blood cells, divided into two main types: lymphocytes, which create antigens for specific pathogens and kill them or escort them out of the body; and phagocytes, which ingest harmful bacteria. White blood cells not only attack foreign pathogens, but recognize these interlopers the next time they meet them and respond more quickly. Many of these immune cells are produced in your bone marrow but also in the spleen, lymph nodes, and thymus, and are stored in some of these tissues and other areas of the body. In the lymph nodes, which are located throughout your body but most noticeably in your armpits, throat, and groin, lymphatic fluid containing white blood cells flows through vein-like tubules to escort foreign invaders out.

5. The spleen helps your immune system work.

Though you can live without the spleen, an organ that lies between stomach and diaphragm, it's better to hang onto it for your immune function. According to Adriana Medina, a doctor who specializes in hematology and oncology at the Alvin and Lois Lapidus Cancer Institute at Sinai Hospital in Baltimore, your spleen is "one big lymph node" that makes new white blood cells and cleans out old blood cells from the body.

It's also a place where immune cells congregate. "Because the immune cells are spread out through the body," Vance says, "eventually they need to communicate with each other." They do so in both the spleen and lymph nodes.

6. You have immune cells in all of your tissues.

While immune cells may congregate more in lymph nodes than elsewhere, "every tissue in your body has immune cells stationed in it or circulating through it, constantly roving for signs of attack," Vance explains. These cells also circulate through the blood. The reason for their widespread presence is that there are thousands of different pathogens that might infect us, from bacteria to viruses to parasites. "To eliminate each of those different kinds of threats requires specialized detectors," he says.

7. How friendly you're feeling could be linked to your immune system.

From an evolutionary perspective, humans' high sociability may have less to do with our bigger brains, and more to do with our immune system's exposure to a greater number of bacteria and other pathogens.

Researchers at the University of Virginia School of Medicine have theorized that interferon gamma (IG), a substance that helps the immune system fight invaders, was linked to social behavior, which is one of the ways we become exposed to pathogens.

In mice, they found IG acted as a kind of brake to the brain's prefrontal cortex, essentially stopping aberrant hyperactivity that can cause negative changes in social behavior. When they blocked the IG molecule, the mice's prefrontal cortexes became hyperactive, resulting in less sociability. When they restored the function, the mice's brains returned to normal, as did their social behavior.

8. Your immune system might recruit unlikely organs, like the appendix, into service.

The appendix gets a bad rap as a vestigial organ that does nothing but occasionally go septic and create a need for immediate surgery. But the appendix may help keep your gut in good shape. According to Gabrielle Belz, professor of molecular immunology at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, research by Duke University's Randal Bollinger and Bill Parker suggests the appendix houses symbiotic bacteria that are important for overall gut health—especially after infections wipe out the gut's good microbes. Special immune cells known as innate lymphoid cells (ILCs) in the appendix may help to repopulate the gut with healthy bacteria and put the gut back on track to recovery.

9. Gut bacteria has been shown to boost immune systems in mice.

Researchers at the University of Chicago noticed that one group of mice in their lab had a stronger response to a cancer treatment than other mice. They eventually traced the reason to a strain of bacteria—Bifidobacterium—in the mice's guts that boosted the animals' immune system to such a degree they could compare it to anti-cancer drugs called checkpoint inhibitors, which keep the immune system from overreacting.

To test their theory, they transferred fecal matter from the robust mice to the stomachs of less immune-strengthened mice, with positive results: The treated mice mounted stronger immune responses and tumor growth slowed. When they compared the bacterial transfer effects with the effects of a checkpoint inhibitor drug, they found that the bacteria treatment was just as effective. The researchers believe that, with further study, the same effect could be seen in human cancer patients.

10. Scientists are trying to harness the immune system's "Pac-Man" cells to treat cancer.

Aggressive pediatric tumors are difficult to treat due to the toxicity of chemotherapy, but some researchers are hoping to develop effective treatments without the harmful side effects. Stanford researchers designed a study around a recently discovered molecule known as CD47, a protein expressed on the surface of all cells, and how it interacts with macrophages, white blood cells that kill abnormal cells. "Think of the macrophages as the Pac-Man of the immune system," Samuel Cheshier, lead study author and assistant professor of neurosurgery at Stanford Medicine, tells Mental Floss.

CD47 sends the immune system's macrophages a "don't eat me" signal. Cancer cells fool the immune system into not destroying them by secreting high amounts of CD47. When Cheshier and his team blocked the CD47 signals on cancer cells, the macrophages could identify the cancer cells and eat them, without toxic side effects to healthy cells. The treatment successfully shrank all five of the common pediatric tumors, without the nasty side effects of chemotherapy.

11. A new therapy for type 1 diabetes tricks the immune system.

In those with type 1 diabetes, the body attacks its own pancreatic cells, interrupting its normal ability to produce insulin in response to glucose. In a 2016 paper, researchers at MIT, in collaboration with Boston's Children's Hospital, successfully designed a new material that allows them to encapsulate and transplant healthy pancreatic "islet" cells into diabetic mice without triggering an immune response. Made from seaweed, the substance is benign enough that the body doesn't react to it, and porous enough to allow the islet cells to be placed in the abdomen of mice, where they restore the pancreatic function. Senior author Daniel Anderson, an associate professor at MIT, said in a statement that this approach "has the potential to provide [human] diabetics with a new pancreas that is protected from the immune system, which would allow them to control their blood sugar without taking drugs. That's the dream."

12. Immunotherapy is on the cutting edge of immune system research.

Over the last few years, research in the field of immunology has focused on developing cancer treatments using immunotherapy. This method engineers the patient's own normal cells to attack the cancer cells. Vance says the technique could be used for many more conditions. "I feel like that could be just the tip of the iceberg," he says. "If we can understand better what the cancer and immunotherapy is showing, maybe we can go in there and manipulate the immune responses and get good outcomes for other diseases, too."

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