Making Sense of Pregnancy: What Experts Want you To Know About Your Body

 Many pregnancy complications cluster around issues with the placenta, the first fetal organ to form in a pregnancy. Here at the end of 2025, this organ still holds a significant amount of mystery. It's a wily organ that comes in many different forms across the animal kingdom. Even looking at how other mammals have handled the job of nutrient delivery, gas exchange, and waste removal during pregnancy, suggests a diversity of ways these jobs can be managed, emphasizing different benefits and costs in a pregnancy.

Looking at how these benefits and costs show up in a cellular conversation between the placenta and the cells of the maternal uterine lining across a select group of mammals, including humans is a new way to understand this organ.

 How the placenta develops and the ways in which that development affect both the mother and the pregnancy have been a mystery since pregnancy became a subject of study. Much of medicine focuses on the symptoms that come from pregnancy complications and tries to find a way to fix if not the problem, then the symptom. 

Today's guest who looks at pregnancy with an evolutionary biology perspective that asks not only how the system works, but why the system works the way it does i.e. why are human placentas so invasive when other mammals have placentas that are not as invasive. Answers to the why questions can shape the ways in which we manage the how. 

To find the paper we're discussion today, Cell ype and cell signalling innovations underlying mammalian pregnancy, see: https://www.nature.com/articles/s41559-025-02748-x

We all know the placenta as this life giving organ, the first to develop in pregnancy; a critical connection between mother and fetus that sends food and oxygen to the baby and eliminates the fetal waste products. Only recently did I trip over the fact that it takes a minute to make this incredible organ.

How long does it take and while its under construction?

How exactly is the embryo and then fetus being fed ? 

In fact, it takes about eight or nine weeks for your body to build a placenta and then a few weeks to get the hookup to the mother's body, which takes us to roughly the end of the first trimester, 10 to 12 weeks or so.

So if that's the case, you might be wondering: how is that embryo getting food for the first 12 weeks? Doesn't it need food to grow and oxygen maybe. What are we doing with the waste? How is all this managed before the placenta is the onsite perfect and all powerful fetal growth manager in a word, womb milk, or histotroph

This is the subject of today's episode. 

To contact me with questions or suggestions, find me at:

[email protected] or @makingsenseofpregnancy

 Why is an active immune system important both in pregnancy and before pregnancy when you're trying to prepare the uterine lining, AKA, the decidua?

 That was the topic of last week's conversation with Dr. Berg's, and this week we talk about what we do and don't know about how to create a uterine lining that's hospitable to pregnancy, and the challenges of being able to predict when the uterine lining contributes to or detracts from pregnancy opportunity.

  Talk to any person who does research on pregnancy, and you may get a variety of different answers about the source of different pregnancy complications, and at what point in pregnancy we would have to turn back the clock to effectively intervene and increase the chances of a healthy pregnancy? Today's guest dates that time at the period before pregnancy even starts.

She and her colleagues are investigating the importance of the process of creating a uterine lining, AKA, decidualization, that will, if many things fall into place, support implantation, placentation, and ultimately a healthy pregnancy, looking particularly at how our immune systems make our bodies fertile ground. 

Endometrial Decidualization: the primary driver of pregnancy health: https://www.mdpi.com/1422-0067/21/11/4092

   The very important role of a certain type of immune cell called neutrophils in pregnancy is the topic of today's episode. This is a continuation of the conversation we had last week with Dr. Suta NAD Carney, , who  is a researcher at the William Harvey Research Institute, faculty of Medicine and Dentistry at the Queen Mary University of London.

We were talking about, the work she's done to uncover the role of the most common immune cell in your body, the neutrophil in pregnancy, and the way that it might contribute to one of the most common birth defects, which are heart defects.

To briefly recap here, we used to think that neutrophils didn't play much of a role in pregnancy. The research we're talking about today highlights the role of neutrophils. Basically, they direct other immune cells to behave in an anti-inflammatory way, at the point at which the maternal tissue meets the fetal tissue.

If neutrophils aren't around to send signals that generate this anti-inflammatory environment. The environment becomes too inflammatory, which affects the collagen that's protecting the placental barrier. That barrier becomes dysfunctional and maternal immune cells get loose and interrupt.

Placental Inflammation leads to Abnormal Embryonic Heart Development: https://pmc.ncbi.nlm.nih.gov/articles/PMC10022676/

 Many pregnancy complications have a whodunit quality to them. Scientists don't yet understand exactly why things go wrong when they go wrong, but researchers tend to agree at this point that if there are issues with the placenta, the lifeline for the fetus, they can reverberate through the pregnancy into well-known conditions like preeclampsia, intrauterine growth restriction, in some cases preterm birth, as well as playing a role in the most common congenital birth defect, which are heart defects.

When we are looking for culprits for these pregnancy complications, some scientists have considered the role of your immune system in pregnancy, but those who study the immune landscape have left out the most common white blood cell in your body: the neutrophil. Of all the white blood cells in your body, around 60% of them are neutrophils.

They're part of the innate immune system, the first responders, and they're super important in everyday life. And as it turns out, also in pregnancy. Today's guest talks about the critical role played by the neutrophil in placental development and downstream in fetal cardiac development.

Dr. Suchita Nadkarni: https://www.qmul.ac.uk/whri/people/academic-staff/items/nadkarnisuchita.html

Placental Inflammation leads to abnormal fetal heart development in the journal Circulation: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061934

Neutrophils induce proangiogenic T cells with a regulatory phenotype in Pregnancy in PNAS: https://www.pnas.org/doi/10.1073/pnas.1611944114

 Miscarriage and the failure of an embryo to implant are often attributed to issues with an aggressive immune system. Today I'm gonna tell you some stories about your immune system, and in particular how your immune system behaves in pregnancy, TLDR, you could not get pregnant without significant immune activity.

Your body is reliant on your immune system to help it manage the development of a genetically distinct person inside the confines of your body. The immune system is important for many different stages of development, and different players are critical at different times. Today we'll focus on the first step in this process. The first meeting of the uterine lining and the embryo. 

Conversation with Dr. Jan Brosen's about the specific preparation of the uterine lining for pregnancy:  

(part 1) https://podcasts.apple.com/us/podcast/understanding-miscarriage-through-evolutionary-biology/id1779600854?i=1000730772552

(part 2) https://podcasts.apple.com/us/podcast/your-uterine-lining-determines-if-and-how-a/id1779600854?i=1000731948247

 If you wanna know what factors contribute to miscarriages, you need to understand what factors contribute to and detract from making the uterus into a hospitable place for pregnancy, both implantation and development. My guest last week, Dr. Jan Brosens, spoke about some of the key conditions that make implantation and development more and less likely, namely the presence of the just right mix of endometrial cells, some of which are progesterone responsive and progesterone resistant. But a fuller picture of the process suggests that there are other critical dimensions in this process of making the uterus hospitable. It's not just timing, but location that's important. 

Since women have been having babies they've experienced miscarriages. For nearly as long, we have not had a useful way to address miscarriage. Often doctors shrug at your first miscarriage and say it's a normal part of pregnancy. And if it arises because of aneuploidy, the fertilized egg has the wrong number of chromosomes, at this point there is not much we can do about that. 

But there are many routes to miscarriage. Today's guest is working to better understand other mechanisms at play in miscarriage. One of his guiding principles is to recognize that pregnancy in humans works according to its own rules. Adaptations that the human body has made that allow for a 9 month relationship between a fetus developing entirely inside it's mother's body don't exist in any other part of the body. Take, for example, the case of the placenta. there are a class of cells in the placenta that rapidly divide, invade uterine tissue and evade the immune system; this is critical to the development of a maternal fetal interface, but a similar pattern of cell growth outside of the context of pregnancy is often called cancer.  

Understanding how human reproduction has evolved to address the challenge of a long pregnancy inside a woman's body has guided today's guest in his work to identify the specific factors that contribute to or prevent implantation, pregnancy and miscarriage.

Here's a link to the 2025 paper in Science Advances with more details: https://www.science.org/doi/10.1126/sciadv.adv1988