Crossroads: The Last Organ Frontier: How the Placenta Holds the Key to Maternal-Fetal Health

I’m going to be talking today about
something that was important to all of us at least at one point in our
lifetimes and that topic is pregnancy. You may have heard or read in the news
lately a lot of reports about how maternal mortality is particularly high
in the United States and that it’s rising which is a an outlier amongst
developed nations. And this is a problem that’s particularly acute among certain demographics like African American women. The other thing that I think has been hitting the national attention a lot lately is just really how common miscarriage is and I think that’s really becoming more of a
discussion point. So I study the organ that’s at the center of all of this. It’s where you have millions of years of evolution and lots of fascinating biology converging and this organ is called the placenta. It’s this disc-like structure that is the interface between the mother and the
fetus during pregnancy. So it serves a whole variety of different functions. It attaches the fetus to the uterus and it also serves as the fetus’ liver and
lungs and intestines and kidneys during pregnancy. So it’s mediating nutrient, gas
and waste exchange. It also has to ensure the success of the pregnancy itself by secreting a lot of important hormones and also protecting the fetus from
infections. And yet, at the same time, it also has to be able to ward off
rejection from the mother’s immune system. So, because this organ is a fetal organ, it can in a way be thought of as an organ
transplant. And not only is it like an organ transplant, the placenta also bears
some similarities to cancer in that it needs to invade the uterus in order to
establish itself and to carry out all of those different functions that I just
mentioned. And this invasion doesn’t stop just at the uterus. What’s really interesting to me and quite terrifying also is that placental cells make their
way into maternal circulation. They’re there in quite abundant numbers during pregnancy and they typically stay around for decades after birth and very rarely they will pop up as placental cancers much later in life in women who have
had children before. What I’m interested in is this process of placental invasion. So what I’ve been doing is taking my background in biochemistry and
molecular biology with my adviser Julie Baker’s background in placental biology and genomics and we’re really hoping to bring those two avenues of thinking
together in order to hopefully address some of the questions in prenatal health
and push the field forward. But one thing I want to first mention
about the placenta is that there’s, unfortunately, not quite a lot known
about it so in spite of how important it is to reproduction and to maternal fetal health and also just how interesting it is as an organ, it’s really understudied
and underappreciated. So it’s often referred to as the afterbirth
as you may have heard and it’s just simply discarded after delivery. And
because so little is known about it some people have taken to calling it the last organ frontier, hence my title for the talk today. And this lack of knowledge can really be quite dangerous. So I had a friend who almost died and another friend who almost lost his baby because of placental disorders. And, unfortunately, their experiences were hardly unusual. So about 10 to 20 percent
of pregnancies are affected by some kind of placental disorder. And really, by and
large, we don’t fully understand what leads to those disorders and how to
tackle them. Now as I mentioned earlier, there’s this cancer-like and very tightly regulated process of invading the uterus and this is the process that
I’m most interested in. Because this is so fundamental for establishing the placenta, you can imagine that most placental disorders arise from some kind
of defect in this process. So, a couple of diseases that you may have heard of, such
as pre-eclampsia and placenta accreta, are really defects in this process of
invasion. The disease that I study, placenta accreta, is where the placenta overinvades through the uterine wall sometimes even entirely through the
uterus and into neighboring organs, such as as the bladder or the rectum. And this can lead to a whole litany of clinical problems, such as damage to those neighboring organs, massive maternal hemorrhage at birth, hysterectomy (which currently is the only treatment for accreta) and even maternal death in as many as seven percent of cases and fetal death in as many as nine percent of cases. And so this is quite a serious problem today in the United States, especially because one of the primary risk factors for accreta is a history of prior C-section. So C-sections account for approximately 30% of deliveries today. That rate is continuing to rise in the US in spite of a lot of efforts to decrease that rate. And so with that there is a projected rise in the number of future accreta cases. In certain parts of the world, C-sections are as common as 80 to 90 percent of deliveries. So it is really becoming a very serious global health problem. So what I’m doing for my research is to try to identify and characterize molecular signatures of this disease. I’m looking at tissues and blood samples collected from patients with accreta. And thus far we have found some very encouraging preliminary results and are following up on that and trying to understand how the disease really happens. At the same time I’m also working to develop a mouse model of the disease so that we can really understand how this disease progresses over time
and so that it would potentially serve as a future platform for testing,
diagnostics and treatment. So I’m really excited about some of the work that we’ve been doing there. And I just really want to underscore the importance of more research in this field. I think there’s a real tremendous need for a better understanding of the placenta and not only is it really critical for improving our understanding of maternal fetal health, but the placenta, because of its so many interesting parallels to other cellular and tissue processes, I really think it’s a unique model system for understanding evolution, development,
cancer biology and immunology. So I’m really looking forward to being able to push this work further, hoping to see that this will lead to a world with healthier pregnancies and healthier lives.

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