The Mystery of Childbirth Is Finally Being Unravelled

0:01This episode is brought to you by Google Chrome. You think you know a browser, but Gemini and Chrome? That's new. It can help you with practically anything on the web, like restoring a vintage motorcycle from a 50-page restoration block, or finally break down that long article you've had open for weeks. Gemini and Chrome is here for it. Ready to make anything online make sense? There's no place like Chrome. Check responses set up required, compatibility and availability varies 18+. Today we're discussing one of my favorite examples of evolutionary biology, and it's not an insect. It's a human baby.

0:33The human baby. And specifically the drama, the absolute drama that occurs at the birth of a baby. That is the right way to put it. I can confirm that the late stages of pregnancy and the whole business of labour is wild. Well, I like the idea that there's a battle between the foetus and the mother over nutrition, but also over when to come out, when to get out. And it's almost shocking, isn't it, to describe that relationship between mother and baby as a battle. But evolutionarily speaking, that's what it is. Well, they call it the maternal-fetal conflict. But a new discovery that we're going to get into shows that the mother transfers mitochondria to the uterus before birth.

1:17And as we know, mitochondria are the power packs of the cells. They're the things that power our muscles, give us energy. and so she does that to power up the muscles of the uterus to kick start the process of birth. That's an incredible discovery and part of that big big question about what actually calls time on pregnancy and says it's time to get the baby out and that's what we're getting into today on this episode of The World, The Universe and Us from New Scientist. I'm Dr Penny Sarshing and I'm Dr Rowan Hooper. So one thing you may not realise until you have a baby is that the end of pregnancy is this big uncertain waiting game.

1:53So even though you have your due date, realistically you could expect your baby to arrive somewhere in a month-long period around that due date. Not ideal, is it? It's not very useful for planning. But this is part of the battle, isn't it? Because the baby wants, in evolutionary terms, it wants to stay inside the mother as long as it possibly can, whereas the mother, the mother's body, wants to get the baby out. And the mother's idea of when to give birth doesn't necessarily align with what the baby's opinion on this is. And we're going to get into that. But then there's also this mystery of what initiates labour.

2:28And for a long time, we really haven't known what kickstarts that process. But now there's growing evidence that it's actually the immune system that presses the go switch for the onset of labour. And what's really exciting about that is because if we know what's actually turning it on, it could potentially give us ways to develop drugs that prevent premature birth, preterm birth. and also maybe to even predict exactly when you are likely to have that baby. So to talk about this, we're joined by Alice Klein, who also has first-hand experience of waiting for babies to come out. And she's been reporting on this new finding.

3:01Alice, why has it taken us so long to work out what actually triggers labour and why has there been such a mystery around it? Well, basically a lot of what we know about the labour process comes from studying other animals like mice and sheep. And in most of them, the trigger for labour is pretty simple. When the baby's finished growing and ready to come out, the pregnant female stops producing a hormone called progesterone. As this hormone drops, it tells the genes needed for labour to turn on and then that gets things moving. But in humans, progesterone levels in the blood don't actually fall when labour starts.

3:33So that's something that has really perplexed scientists for a long time. And so also humans walk on two legs and sheep and mice walk on four. So we're going to get into that whole aspect of it. But this new research then suggests that in humans, it's the immune system that activates labour. And that seems so surprising, isn't it, for the immune system to be involved in this process? What led people to suspect it was, Alice? Well, one of the first clues was the finding that the human uterus is packed with immune cells. So scientists began wondering, well, what are they doing there? And then some groups started finding that towards the end of pregnancy, the uterus starts releasing these signaling molecules called chemokines and cytokines into the mother's blood.

4:18And they found the role of these signaling molecules is to recruit immune cells called monocytes, which are a type of white blood cell, and bring them into the uterus. You can imagine it can be a dangerous thing to do to bring immune systems into a place where there's a foreign body, right? The baby is made of foreign tissue. And so in some ways you could look at the fetus as a parasite, right, that the immune system might want to attack it. Yeah, I mean, do your children know that you think that they are parasites? I hope they're not going to listen to this episode. But, yes, the fetus is actually held separate from the uterus by the placenta and a lining called the decidua.

5:03and also the mother's immune system is held in check by these specialised cells called regulatory T cells. But yes, there is a conflict and sometimes it doesn't always work to hold the system in check. So why are these white blood cells, like, okay, there is that risk, but why, so why are they swarming into the uterus there? What are they up to? So a group at Mount Sinai Hospital in Toronto found that these white blood cells accumulate in the muscle layer of the uterus. And once they're in the muscle, they actually turn into a different kind of immune cell called an inflammatory macrophage. So then the next thing to do was to find out what these macrophages were doing in the uterus muscle.

5:44So how did they do that then? Well, they just took some of these macrophages and they incubated them with uterus muscle cells, which they got by taking biopsies of women when they had cesarean sections at full term. So they had these macrophages and uterine muscle cells in a dish and they just sort of put them there and thought, okay, what are they going to do? And amazingly they found that the macrophages started forming these tiny tubes and sending them out so they could grab onto the uterine muscle cells. What were these tubes doing? What were they for? I know it does sound a bit alien-like.

6:19But so in other systems, sometimes you get these tiny tubes forming between cells and they are sometimes used to transfer mitochondria. So the researchers wondered if the same thing was happening here. And to find out, they added a dye to the mitochondria. And sure enough, they were able to see mitochondria being delivered from the macrophages, the immune cells, to the uterine muscle cells through these little tubes. and they've got videos of this and it's amazing because you can see the mitochondria streaming between the cells. I think this is absolutely amazing. So I knew that you could get these microtubules, but I had no idea that the body could shuttle mitochondria through.

7:03I saw some of the pictures as well, like a little gondola going along. They call it a gondola carrying the mitochondria across the tubules. I always thought mitochondria were completely just embedded in their host cell. But now we're looking at them like you can herd them through, like livestock. Yeah, or like inject them into a cell that needs a bit of a boost. Yeah, that's amazing. And so, I mean, given what we know about mitochondria giving energy, I can guess why the body wants to put them into the uterus muscle. Yeah. I mean, if you think about labor, it's this hugely energy intensive process.

7:39You need that muscle part of the uterus to contract really strongly over and over again to try to push out the baby. Having done this three times myself, I mean, I was shocked by how powerful it was. It felt like an earthquake ripping through me. And as you say, mitochondria, they're like the battery power of cells. They provide the energy. So the most likely explanation is that the immune cells donate lots of mitochondria through these little tubes into the uterus muscle to give it that extra energy it needs for labor. And in line with this, the researchers found that levels of ATP, you know, the energy providing molecule, that increased in the muscle cells after they received the mitochondria from the immune cells.

8:21Just amazing. So does that mean then compared to other mammals, our labour seems to be triggered by this sort of injection or shuttling of mitochondria rather than the drop in progesterone you mentioned? Well, so here's another really interesting thing. The influx of mitochondria also increased levels of an enzyme that breaks down progesterone. So this drop in progesterone is probably what actually signals the onset of labor in humans because as we discussed before, it's known that a sharp drop in progesterone is what turns on the genes needed for labor. And in other animals, progesterone drops all over the body.

8:57But maybe in humans we've got this really precise, elegant mechanism where progesterone is just dropping in the muscle cells of the uterus and that's what kicks off the contraction. It's interesting, isn't it? Because there's also evidence that the immune system might be involved in human menstruation as well, triggering the mass die off of the cells that enable the shedding of the lining. So clearly the immune system and the uterus in people, in humans, have a close relationship that we're only just beginning to understand. But anyway, in regards to the labour activation stuff, can we use this?

9:32Can we kind of apply this to pregnancies in some way? Well, the first thing is that if we can understand what triggers labour, then we might be able to stop it when it happens too early, as in the case of preterm births. And that would be great, wouldn't it? Because preterm births, which are ones that occur before 37 weeks, there are all kinds of problems. Organs might not yet be fully formed yet. There can be various health and developmental issues that happen with preterm babies. There are already drugs though, aren't there, that you can give people if they start to go into labour too early.

10:03Yes, and they are called tocolytics and they work by relaxing the uterus so that it doesn't contract. But they tend to only delay labor for a short time, maybe up to a few days. So, for example, a few years ago when my husband was working for the flying doctor service in Australia, he needed to transfer a woman who was pregnant with twins from the country to the nearest city because she started going to labor at just 24 weeks, I think. and so she needed to get to a hospital with neonatal intensive care and she'd already been given these tocolytics to try to halt the labour but as you can imagine he was absolutely sweating because he was worried that they would wear off mid-flight and he'd have to deliver these two very preemie babies on a tiny plane.

10:50Oh my God. But fortunately they did manage to get her to the hospital without her going to labour and her babies were okay but if we had drugs that could delay labour, reliably for much longer, that would be great. I will direct listeners to that podcast you did about your husband's adventures as a flying doctor. Amazing stuff. He doesn't actually fly the plane, right? He was in the back when there was a pilot flying it. I think that would be a bit much to ask, to fly the plane and to deliver two babies. It would be a bit much. All right. So look, if the immune system is in charge of when labour starts, does that give us any clues to how we could stop it if we need to stop it going off too early?

11:35Well, the Mount Sinai group that figured out all these steps in how the immune system triggers labor has already experimented with using a drug called a broad spectrum chemokine inhibitor. And its job is basically to block the chemokines that recruit those white blood cells to the uterus at the beginning, which theoretically should block the rest of the process leading to labor. And at this stage, they've only tested it in four macaques, which had bacterial infections that would normally trigger preterm births, but none of them went into labor. So it's promising, but it hasn't been tested in humans yet.

12:09And then what about this unpredictability of when you give birth? Is there any way we could use this to develop like a blood test that could tell you where your immune cells are at and how soon you'll be going into labour? That's another thing that this Mount Sinai group is working on. So at the moment, they're doing a large study with pregnant women who come in with possible signs of going into labour early. they're taking blood samples from then and looking to see if they can find signatures of immune cells that show if they really are going into labor or if it's a false alarm and hopefully as this gets more precise you might also be able to give blood tests to pregnant women who've reached full term to see if they're likely to go into labor imminently or if it's still a way off because that could inform their decision about whether or not to have an induction because i mean i've been through this myself.

12:59And at the moment, you just sort of go in and you have your cervix checked to see if it's starting to open up yet. But it's a bit of an imprecise art, and it's not the most fun examination to have. So it would be great if you could just have a blood test that could tell you with pretty good confidence if your baby's coming soon or if they're going to stay in there for much longer. Time for a quick break. Cancer remains a leading cause of death globally. AstraZeneca has a bold ambition to one day eliminate cancer as a cause of death, and they aim to do this with an oncology strategy that connects earlier detection with new drug therapy combinations and transformational technologies.

13:38To find out how, search New Scientist CoLab AstraZeneca to read the full feature. Sponsored and co-developed by AstraZeneca. This episode is brought to you by Google Chrome. You think you know a browser, but Gemini and Chrome? That's new. It can help you with practically anything on the web, like restoring a vintage motorcycle from a 50-page restoration block, or finally break down that long article you've had open for weeks. Gemini and Chrome is here for it. Ready to make anything online make sense? There's no place like Chrome. Check responses set up required, compatibility and availability varies 18+.

14:13let's talk about one aspect then of maternal fetus conflict which is why we actually give birth when we do to babies that are simultaneously like big and really painful to deliver yeah but also really helpless and hard to look after yeah so that's the obstetrical dilemma yeah exactly go on yeah and so that's the idea that these these two opposing evolutionary forces a tug of war One is that when we became bipedal, when our ancestors became bipedal, that meant we had to have a narrower pelvis. And then the other side is that we've got really, really big brains. So we actually ideally need a bigger pelvis to get out.

14:50So, you know, we're forcing big headed babies through the smaller gap that we've put on ourselves by being bipedal. Yeah, exactly. And this is a famous explanation for why human childbirth is so painful and also dangerous. a lot of mothers die. And it also suggests we're giving birth earlier while our babies still can get out of our bodies to infants that aren't as well developed as they'd ideally be. But actually, it turns out it may not be as clear cut as all that. Oh, OK. So why else might we give birth when we do? So one idea that I think is quite interesting is another explanation that centres on metabolism.

15:25This is a more recent idea, and it suggests that we grow our babies inside us until we literally can't sustain them anymore. They become too much of a burden on a mum's energetic. The parasite becomes too big. Yeah, basically. I would say that my babies were still a burden on my energetic resources once they came out. I think that's fair. But I don't know. Do we know if this is true yet? Is it so sort of disappointingly? Because I think it's an interesting idea. But in recent years, there have been a few studies that sort of tried to determine how big of an energetic demand a late stage fetus places on the mother.

15:57And the evidence doesn't really seem to be stacking up in favour of this hypothesis. All right. So at the moment, we still do have this obstetric dilemma. Yes and no. So I think it is clear that our narrower pelvis has made childbirth more painful and more dangerous. And there was an Australian study showing that pelvises have been getting narrower. Was that the idea that, so they looked at the width of women's pelvises from 1900 to like current times and showed gradually that the width was getting narrower. And it's the idea that selection is relaxed on that because we have modern medicine and we don't, you know, more women survive.

16:37This is really like a live issue at the moment. It has sort of been cited as an example of really fast evolution. We do see sections and it's removed this selective pressure. But actually, it might be something else. And it might actually be positive selection for narrower pelvises. Yeah, OK. How does that work? Well, like always, we forgot pelvic health. And actually, if you have a narrower pelvis, you might be less predisposed to pelvic injury, pelvic organ prolapse, these kinds of things that are often not talked about, but are very common. And the thinking there is if you have a narrow pelvis, you might be less likely to sustain these kinds of injuries.

17:14And then you might then go on to have more children. Oh, God. OK. So it's... So complicated. Selection is going both ways. Well, yeah. Well, the end result, whatever's happening, is we do seem to be getting narrower and narrower pelvises. But another surprising thing here is that this idea that we give birth to particularly helpless babies because of our narrower pelvises, that could also be wrong too. But they are pretty helpless, aren't they? Yeah. So the science word for this is ultritional. But actually, if you look across all of the other placental mammals, not just kind of monkeys, which are quite amazing when a monkey just kind of comes out and holds on to its mum.

17:52If you look across the piece with mammals, human babies aren't actually particularly altricial. And so this idea that we have these particularly like early born babies, it might just be a distortion of the fact that we sort of measure how altricial a young infant is. by comparing its brain now to the brain that it's going to have. And of course, humans have this amazing extended childhood period where we do all of this extra brain development. So yes, our babies seem very early compared to the brainy adults that we become. But that might actually be just because we have this extra phase of development compared to other mammals.

18:31Wow. So where does this leave us then? I mean, why do we give birth when we do? So the ins and outs of that obstetrical dilemma are still being hotly debated. There's a lot of studies coming out on this at the moment, but it's starting to look at least that the timing of when we give birth isn't that different to what you'd expect from looking at other mammals. So, I mean, obviously, human gestation is divided into trimesters, but you do often hear this talk about how babies need this fourth trimester and we sort of need to recreate the womb for three months once the baby is born. Does that negate that idea, Penny?

19:04Yeah, this kind of blew my mind, actually, because it's this sort of parenting orthodoxy now that your baby is born like three months too early and you have to, you know, mimic the womb. And that's quite a lot of pressure for a new parent, which I don't think is necessarily that helpful. And so, yeah, maybe we do need to rethink this idea of the fourth trimester. Obviously, you kind of want to cuddle and comfort a newborn to help them make that transition into the outside world. but maybe this idea that they're like especially helpless and ideally wouldn't have been born yet is kind of unnecessary but that's really ingrained isn't it yeah the whole idea that our babies are born when they haven't really finished developing yeah because of the obstetric dilemma yeah wow yeah i mean this is all part of this evolutionary tug of war between the mother and the fetus and the bit that i like about it is that is over nutrients the fight over nutrients and so the the fetus wants as much nutrients as it can but the mother wants to hold some back right the fetus wants to maybe sometimes wants to stay gestating longer as well and then the mother ideally wants to yeah because it's in the mother's evolutionary interest to not deplete herself so much that she can't have future children yeah she wants multiple children whereas the fetus doesn't necessarily care about you know its future siblings yeah and this all plays out in the placenta yeah so the placenta what an extraordinary thing this is um i think i can't remember exactly how much but a lot of it is grown by paternal genes so paternal genes are expressed in it in other words the the father's interest has control over this key part of the of the meshing between the fetus and the and the mother and so the placenta literally burrows into the mother's tissues uh and and tries to you know increases the size of the blood vessel so more blood comes in it secretes insulin so that the mother is forced to make her her blood more sugary which the fetus wants and that can have bad consequences for the mother yeah gestational diabetes so yeah this there is this extraordinary tug of war yeah and it's amazing how sort of essential the placenta is but sinister and but it does eventually start to break down towards the end of pregnancy which is one reason why they and juice babies that have been hanging around so long that it's probably time to get them out.

21:26Do people still consume the placenta? I mean, I know in some cultures they do. And I did consider it. Really? Oh, yeah. Because I've not eaten meat for decades, right? And I thought eating the placenta would be my only chance really to ethically eat meat. Did you have a good look at it when it came out? Well, that's what instantly put me. No, no. But I'd been researching recipe. oh how am I going to cook this and yeah but instantly no. I think people do still freeze dry it and put it in capsules Alice do you know anything about this? Yeah you can get them turned into pills yeah it was not for me I do know people have done that.

22:04Should we leave it there? Let's that's all for this episode thanks to our guest Alice Klein and thanks to you for listening and do subscribe as always follow wherever you get your podcasts bye for now.

22:22Thank you.