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Perfect. Can you guys just help me double check if it's recording and you can see my screen. OK. That's fine. All right. We'll just make a start then. So, hi everyone. I'm V at the end with a medic and today I'll be doing environmental impacts, postnatal and child development. So just a caution, this is actually three lectures um kind of lumped into one lecture. So it can be very, very content heavy as you guys know with repro. Um So I apologize in advance if it's a lot of speaking. Um they're not very interactive but, but that's just the nature of these topics. Some of these are things you also will have to just memorize. So I'll just point out some things that came out in our exams and hopefully that will let you guys know which ones are more important to remember and which ones are not. So let's jump right in both. So these are the title that we, we're covering early life impacts the mechanisms of early life, programming, postnatal growth and hormonal changes in um childhood and puberty and developmental domains. And the topics I'll be covering are so hope these look familiar developmental origins of health and disease. So Doha linking Doha to biology. So we were looking at certain mechanisms through which Doha can act. Um then we look at the transition from prenatal to postnatal growth. So what are the different factors that affect prenatal and postnatal growth? And how do they affect them um differently as well as the different phases of growth? Um And then we'll all be also be looking at developmental domains and developmental delay right at the very end. So um we're gonna start out by just defining what the Doha hypothesis is and just look at a very simple application or, or kind of how it was discovered. So do had stands for developmental origins of health and disease. What it basically means is it's in, it's in the word, it's a developmental origin of health and disease you experience in the future as an adult. Basically, we're um hypothesizing that the adult life is actually programmed in early life even before birth when you're in the womb. And this, there was actually a key study by Barker and colleagues, which found out that on average adults who had a coronary event. So an M I for example, had been small above and thin at two years of age. So basically, they have been very small, um possibly malnourished, undernourished as a child, but thereafter they put on weight rapidly. So possibly due to increased availability of nutrition, increased accessibility to nutrition, et cetera. So um what they found out was that the risk of coronary events was not actually related to the uh childhood BM I at any point in time rather, it was linked to the rate of change of childhood BMI. So how did the childhood BMI I change over a period of time? That was what was correlated with the risk of coronary events rather than the BM I attained at any particular age of childhood. So in this graph, you can see that. So this black line, if there was a child, say that started at this kind of trajectory, right? Um They were quite small and they were kind of in the 10th centile in terms of their weight um when they were around two years old, but then they experienced massive um kind of catch up growth. So this is the key word, catch up growth and you can see that they're now in sort of the 91st cent. Um So it's at this rate of change of um BM I this catch of growth that correlates later with cardiovascular events later on in life. So it's not just it's not the BMI of a child at any particular point in time. It's um the rate of change of childhood BMI, right? So this is nicely summarizing what I was talking about in the previous slide, basically under nutrition in or when you are very, very small child and overnutrition as a child as you're growing up increases your risk of metabolic syndrome. And the reason for this is because there is a mismatch, you're prepared for undernutrition because you don't, you receive undernutrition in UTR. But um as you grow up, you receive oral nutrition. So that's a mismatch and that's an imbalance and this creates the risk of a metabolic syndrome and increases your risk of cardiovascular events. So the link between the increased risk of cardiovascular events and kind of the undernutrition um in nut and over nutrition as a child is the metabolic syndrome. So how exactly does do hard work though? Because you know, that needs to be a possible mechanism through which this actually happens. So what um kind of we hypothesize is that this happens, this can happen through predictive adaptive responses. So again, another keyword or pa, so pa are basically developmental adaptations taken by the fetus to prepare itself for the future environment. So while it's in the womb, it's like, right? Ok. Um These are the things that um I'm experiencing. So whatever it's envi the environment it's experiencing while it's in the womb, that's the environment that it's going to take, that it's going to think it's going to be born into. So these productive predictive adaptive responses um prepare the fetus for its future environment. So they might not benefit the fetus immediately, but they are taken in anticipation of the environment they will be exposed to, right? So this is what I mentioned previously a mismatch between the predictive adaptive response of the external environment. So, if there was under nutrition in neutral, for example, the fetus kind of um kind of uh undergo certain epigenetic changes that make it uh easier to kind of stall um nutrients because it only receives very little. So uh the it goes epigenetic reprogramming um so that it can store nutrients more easily. But when it's born to the external environment, it actually experiences over nutrition. Um So, and with coupled with the fact that it's undergone this epigenetic reprogramming to store nutrients very easily. It's then going to cause excessive storage of nutrients, obesity, et cetera. So basically, the fetus is maladapted when it's exposed to an environment that doesn't match the environment that it was exposed to as it was a fetus. And again, predisposes you to metabolic syndrome, predisposes you to coronary events, potentially increases your risk of ill health later on in life. So, um from the graph, you can see that if um in the development environment, um you are at 0.8. So this is what you were exposed to. But um after you're born, you are kind of exposed to a great amount of nutrition. You can see that this kind of causes mal adaption. And this is an, this gives you an increased risk of disease because this was an unpredicted excess of nutrition. And one way which this process happens is through epigenetic processes, but we'll talk about more, talk more about that in later slides, right. So what kind of diseases actually can be correlated to these um to the do had hypothesis and kind of uh a mismatch um causing your predictive adaptive responses to not be the most ideal. So everything from cardiovascular disease, type two diabetes, lung disease and et cetera. Um and basically the challenges again, just reiterating what you said earlier phase for the fetus in UTR can have a lasting impact on its health. Um And this is a DHE hypothesis. And I mentioned we need to look at the mechanisms through which this happened. So, three main mechanisms through which the features is programmed in to prepare itself for the outside world. Number one hormonal effects, what we'll specifically be focusing on is gluco coid over exposure that causes a negative effect on the fetus. The second mechanism is epigenetic modification. So do take note that a fetal environmental exposure, it doesn't change the fetal DNA that's fixed, it changes the way the DNA is being expressed. So it causes changes to epigenetics, not the genetics itself. And three, it causes irreversible developmental changes in terms of the fetuses, its organ size and structure because once a certain organ has been shaped in a certain way, has formed in a certain way, it's difficult for it to be kind of reshaped. So um this kind of causes irreversible developmental changes, right. So let's jump right in into the very first one hormonal effects. And as I mentioned, glucocorticoid over exposure. So how is fetal glucocorticoid exposure controlled? It's actually regulated.