[00:00:00] Dr Renee White: Knowledge is power, and we are all about empowering the mamas of the world. In each episode, we will unravel and interpret the latest research and evidence-based practices for pregnancy, postpartum, and motherhood. [00:00:15] As mums and researchers ourselves, we have experienced firsthand the overwhelming complexity of information myths and those classic old wives tales.

[00:00:27] Dr Renee White: I'm Dr. Renee White, and this is the. [00:00:30] Science of motherhood. Hello and welcome to episode 191 of The Science of Motherhood. I am your host, Dr. Renee White. Thank you so much for joining me today. Today's episode is proudly brought to you by Fill Your [00:00:45] Cup, Australia's leading doula village now. If you don't know what a doula is, it's not a jeweler.

[00:00:54] Dr Renee White: I had this conversation with someone the other day. I was having a chat with them and they said, what do you do? And I said, I'm a [00:01:00] doula. And they said, oh my goodness, you must have the most beautiful pieces of like rings and necklaces. And I said, no, no, no. A doula with a D, not a jeweler. And then I went on to explain exactly what a [00:01:15] doula is.

[00:01:16] Dr Renee White: So for all those playing at home, you probably, some of you might think, what is a doula? A doula is essentially, we're the Mary Poppins of mothers. In a nutshell, we're non-medical professionals. [00:01:30] We are your birth BFFs. We support you during IVF. I did that last year. During pregnancy, during birth, during postpartum, [00:01:45] we hold your hand.

[00:01:47] Dr Renee White: We are your birth cheerleaders. We essentially make beautiful, delicious meals for you. We hold your baby while you go and have a long hot shower. [00:02:00] Or a sleep so you can recover faster and I guess have those beautiful deep bonds with your baby. But ultimately, we are there to assist you to [00:02:15] embrace motherhood with confidence.

[00:02:17] Dr Renee White: Not the chaos. And we have been supporting mums across Australia for the past five years now, which is just amazing. If you are [00:02:30] new, you might, you might be thinking, hold on a minute. I like the sound of this doula thing. Can I have a doula? Well, if you are in Hobart, Melbourne, [00:02:45] Geelong. Newcastle, Sydney, Perth, Brisbane, the Gold Coast, and now Central Coast.

[00:02:55] Dr Renee White: Then I'm gonna say yes, you can absolutely have a fill your cup doula. [00:03:00] As part of your pregnancy, birth, and postpartum. We've got a huge team now across Australia, the most amazing women. I'm so lucky to work alongside these beautiful people. All professionally [00:03:15] trained. They, they just get it right. They've been there, done there, got the t-shirt.

[00:03:21] Dr Renee White: If this sounds amazing to you, if you wanna take the mental load off birth and pregnancy and postpartum. You [00:03:30] want someone who you trust, who you know can answer all those questions. When you're feeling overwhelmed, stressed out, you might not have friends and family close by. Your partner might be running their own business and they just [00:03:45] cannot take a extended leave when bubby arrive.

[00:03:49] Dr Renee White: Then a doula is perfect for you. That is textbook for us. If you're interested in learning more about our services, have a look in the show notes. There'll be a link, but [00:04:00] otherwise it's i fill your cup.com. Pop over to our website. Hit the services tab, and you can have a look at our birth doula and postpartum doula services.

[00:04:12] Dr Renee White: Alright. Today [00:04:15] we are diving into groundbreaking research that could revolutionize how we understand and potentially prevent one of the most common hormonal disorders affecting women of reproductive age. [00:04:30] We are talking about polycystic ovary syndrome or PCOS as it's typically, uh, referred to as now.

[00:04:39] Dr Renee White: PCOS affects up to one in 10 women worldwide. [00:04:45] And if you have PCOS, you know, the frustration, the irregular periods, you know, difficulty conceiving, um, unwanted hair growth, weight gain, you know, increased risks [00:05:00] of diabetes and heart disease. And for decades we've known PCOS runs in families. But I guess the genetic puzzle pieces.

[00:05:10] Dr Renee White: We've never quite fit together up until recently. Maybe [00:05:15] let's dive into it now researchers in China think they have found a missing piece of that puzzle, and it's not in our DNA sequence itself. So it's actually in chemical [00:05:30] tags that sit on top of our genes controlling which ones get turned on and turned off.

[00:05:38] Dr Renee White: Now these are called, and you might have heard this before, epigenetic markers, [00:05:45] and this new research is suggesting that they might be the key to understanding how PCOS passes mum to daughter. Now before we get, before we get all [00:06:00] excited about potential like cures, we need to examine this research carefully, and that is what we do here at the Science of Motherhood.

[00:06:08] Dr Renee White: We're gonna put our research caps on. We're gonna talk about, uh, what did they actually [00:06:15] find in this study? What does it mean for women with PCOS? And I guess we always need to look at what the limitations are that we need to consider. Always, there is always gonna be limitations to research. If you are [00:06:30] new to the podcast, hello and welcome, so you will, you'll know for after today's episode that we are not just fairy floss and lollipops here.

[00:06:39] Dr Renee White: We talk about the limitations of the research. We like to keep everything above board. Now [00:06:45] straight off the bat, let's start with what we know about PCOS. Now, to be diagnosed, you need at least two or three key features, elevated male hormones like testosterone, irregular, or absent [00:07:00] periods, and what looks like cysts on your ovaries.

[00:07:03] Dr Renee White: Now, though these are actually immature eggs that haven't been released. Now, PCOS clearly runs in [00:07:15] families. If your mother has it, your risk increases significantly. If you're an identical twin and your twin has PCOS, your chance of having it is too is, it's about 70%. [00:07:30] Now, this strong, familial kind of clustering suggests genetic, you know, there are genetics at play, right?

[00:07:40] Dr Renee White: It's, it's, it's got a major role. But here's the [00:07:45] puzzle that's frustrated researchers for years, despite extensive genetic studies, only about 25 to 30 genetic mutations have been linked to PCOS. And these explain just a [00:08:00] tiny fraction of the inheritance pattern. Now in a media release, Dr. Elizabeth Sterner, Victorian from the Karolinska Institute puts it, you know, [00:08:15] these known genetic, uh, factors explain, quote unquote, just a small fraction of the inheritance.

[00:08:24] Dr Renee White: Now, this is where epigenetics comes in. We're gonna get a little [00:08:30] sciencey here, people, so here we go. Think of your DNA as a massive library of books. Okay, so they are your genes. Now the epigenetic [00:08:45] markers are like little post-it notes stuck on those books telling the cell. Which books to read and which to ignore.

[00:08:57] Dr Renee White: Uh, I guess unlike Genetic [00:09:00] mutations, which change the actual text of the books, epigenetic changes just affect which books get read. Okay. Of course, I'm gonna put a book analogy in there. If you're a long time listener, you'll know. [00:09:15] Now here's what's makes this like really relevant to inheritance. Now, most epigenetic markers get erased when eggs form, like removing all the post-it notes before [00:09:30] passing books to the next generation.

[00:09:32] Dr Renee White: But some markers survive this, you know, erasing process and could potentially be passed from mum to child. And in previous [00:09:45] studies in mice, this is what we have to do in research. We have to start with mice and then work our way up to humans. In previous studies, it's was suggested that this might happen with PCOS, but until now.[00:10:00]

[00:10:00] Dr Renee White: No one had looked directly at human eggs and embryos to see if women with PCOS pass on different epigenetic patterns. Okay so, so that's, that's the background. Now, this is what we have just discovered [00:10:15] from the research. Now the study from the University of China, the research was presented at the European Society of Human Reproduction and Embryology Meeting, and it [00:10:30] represents, I guess, the first direct examination of epigenetic markers in human eggs and embryos from women with and without PCOS.

[00:10:41] Dr Renee White: Now the team from China [00:10:45] analyzed biological material from 228 donors, 133 women with PCOS and 95 without. And they looked at, they looked at the eggs and [00:11:00] three day old embryos examining three specific types of epigenetic markers that I guess control that gene activity. So whether they're turning it on, turning it off, now what [00:11:15] they found was striking.

[00:11:17] Dr Renee White: Women with PCOS had distinctly different patterns of all three types of epigenetic markers in their eggs and embryos and two [00:11:30] of these markers work by making DNA coil more tightly around proteins called histones, essentially silencing the genes. So if you think of your DNA as this [00:11:45] really long piece of cotton and you know, like cotton reels.

[00:11:50] Dr Renee White: You know those cotton reels that we have and they wind up and that's what you have for sewing machines. So the DNA is the cotton and the histones are the actual cotton reels [00:12:00] that actually have the DNA wound around them. So that's just the visual. So they found that the DNA coil more tightly around the, histones essentially silencing them.

[00:12:11] Dr Renee White: Now the third type does the [00:12:15] opposite. It actually loosens the DNA coils to activate the genes, and the researchers found that these PCOS linked epigenetic changes altered the metabolism of eggs and embryos, [00:12:30] and they suggest this could raise the risk of PCOS in the next generation, essentially.

[00:12:36] Dr Renee White: So mothers with PCOS might be passing on epigenetic instructions that [00:12:45] essentially predispose their daughters to developing the condition. But here's where it gets really interesting from a potential treatment perspective. The team used a drug to [00:13:00] reverse these epigenetic changes in the lab, and this suggests that if we could identify the right interventions, we might be able to prevent PCOS [00:13:15] inheritance, which is kind of cool.

[00:13:18] Dr Renee White: One of the researchers from the team, Dr. Zhu, stated in a press release if we can confirm that altering these, histone markers changes PCOS traits in the next [00:13:30] generation will have a powerful target for prevention, end quote. The researchers also suggested that clinicians could potentially use these PCOS related epigenetic markers to select the healthiest embryos during IVF [00:13:45] procedures as well.

[00:13:45] Dr Renee White: So that is a cool kind of add, value add as well. All right guys. Here comes the critical analysis, Baba ba. Uh, so let's pump the brakes a bit, okay [00:14:00] cause this is all sounding really fab, but we need to look at this, you know, with a fine lens and examine this research critically. Now, while these findings are very intriguing, there are several important limitations and concerns we need [00:14:15] to address.

[00:14:16] Dr Renee White: The first one is the evidence gap. Now, this research shows that women with PCOS have different epigenetic patterns in their eggs and embryos, but showing correlation is not the [00:14:30] same as proving causation. I don't know how many times I've said this on this podcast and I see it time and time again on social media.

[00:14:37] Dr Renee White: People jump on correlation and just go, bam, okay that that's what causes that. So we don't yet [00:14:45] have evidence that these epigenetic differences actually cause PCOS in the next generation. And again, Dr. Stenner Virin, who wasn't involved in the study, points this out clearly and she quotes for now, [00:15:00] we just know that those markers are different.

[00:15:03] Dr Renee White: It does not necessarily mean they have a negative effect, end quote. And this is a really crucial distinction, guys like different doesn't automatically mean harmful [00:15:15] okay. So that's the first point, the second the research status. Now, when you are looking at research articles and press releases, you need to see how was this research study presented?[00:15:30]

[00:15:30] Dr Renee White: Now, this study was actually presented at a conference. Okay, not published in a peer review journal and while conference presentations can highlight important preliminary findings, they often lack the detailed [00:15:45] methodology, the statistical analysis, the critical review that comes with publications. Now we're missing key information about sample sizes, statistical significance, effect sizes, potential confounding [00:16:00] factors, and all of those things.

[00:16:01] Dr Renee White: So fingers crossed they are on their way to publishing this amazing data. And then it will be peer reviewed, which means other people within that field who are [00:16:15] experts will be trawling through their data and they will be making sure that everything is schmick up to standard and nothing is missing.

[00:16:25] Dr Renee White: The third, I guess the leap to, to [00:16:30] treatment, the jump from, we found different epigenetic markers to we could prevent PCOS with drugs. It's a bit premature, guys. Okay. So like as scientists, we always. Wanna be able to do that and say we're gonna cure the world. But you know, pump, [00:16:45] pump the brakes, guys. So they showed they could reverse epigenetic changes in a lab dish, but this is vastly different from safely and effectively modifying epigenetic markers in living human beings, especially in the context of [00:17:00] reproduction like that is a big, big feat.

[00:17:03] Dr Renee White: The fourth for me, I guess, is, you know, epigenetic markers controlling gene expressions throughout development. So modifying them could have [00:17:15] an unintended consequence. We don't yet understand. And the idea of using drugs to alter epigenetic patterns in embryos raises some serious kind of safety questions and maybe even some [00:17:30] kind of ethical questions that would really require extensive research to address.

[00:17:38] Dr Renee White: But I guess, you know the bigger picture, PCOS is a really complex [00:17:45] condition. We know that it's influenced by genetics, it's influenced by environment, lifestyle, all other factors. Even if epigenetic inheritance plays a role, it's unlikely [00:18:00] to be the whole story. So I guess despite these limitations, this research, it, it really does open up like an important avenue for investigation and that's what we always love from research.

[00:18:13] Dr Renee White: We love the fact that we [00:18:15] are testing, experimenting, we are answering some questions, but we're coming up with more questions thereafter. And if this data is validated, it could fundamentally change how we think about PCOS [00:18:30] inheritance and prevention. And I guess for women with PCOS, this research might eventually lead to better risk assessment and potentially prevention strategies for your daughters, but honestly, we are [00:18:45] not there yet okay. This is very cutting edge, straight off, you know, the lab bench type of work and I guess current management, lifestyle modifications, hormone treatments, and fertility interventions still remains like, you [00:19:00] know, the standard of care. And I guess the potential discovery of epigenetic inheritance in PCOS.

[00:19:08] Dr Renee White: It represents a really exciting frontier in reproductive health research. It could [00:19:15] explain the missing heritability puzzle and potentially open doors to prevention strategies we never imagined possible. Alright, guys. Until next week, I will see you. [00:19:30] Bye.

[00:19:30] Dr Renee White: If you loved this episode, please hit the subscribe button and leave a review. If you know someone out there who would also love to listen to this episode, please hit the share button so they can [00:19:45] benefit from it as well. You've just listened to another episode of The Science of Motherhood proudly presented by Fill Your Cup, Australia's first doula village.

[00:19:55] Dr Renee White: Head to our website I fill your cup.com to learn more about [00:20:00] our birth and postpartum doula offerings where every mother, we pledge to be the steady hand that guides you back to yourself, ensuring you feel nurtured, informed, and empowered, so you can fully embrace the joy of motherhood with confidence. [00:20:15] Until next time, bye.