What goes on in the lab? 15.4.08

I've joined an ongoing research project here in Tokyo, at Keio University's Faculty of Pharmacy to be exact. The goal is to find out more about how the placenta functions. When a female carries a baby in her womb, the fetus' umbilical cord is connected to the mother via the placenta and so the mother and fetus basically shares the same blood. That means that anything in the mother's blood will also pass through the baby. Luckily, the placenta acts as a barrier between mother and fetus and can actually shut out certain substances - effectively protecting the fetus.

For a woman with a disease or condition requiring her to be on constant medication (HIV, epilepsy, high blood pressure to name a few), there is sometimes a risk that the drug(s) she is taking will pass through the placenta barrier and cause damage to the fetus or slow its development, leading to all kinds of nasty problems or even miscarriage.

With better knowledge about what substances the placenta will and will not block, safer treatments might become possible.

One method of studying the placenta is to use cells from actual human placentas. However, since those cells are taken from normal childbirths, they only give us a picture of the placenta when the baby is ready to be born and that's a lot different from, say, the mid-stages of pregnancy. To better understand how the placenta changes over time, one would have to take cells from different stages of pregnancy. I'm guessing this is not quite ethically feasible, and even if it were I'm sure it would be very expensive. In this case, it's much more practical to use animals.

I've been assigned the task of investigating the passive diffusion properties of the placenta at different stages of gestation, in vivo. This means I will be using live anaesthesized pregnant rats, inject biologically inert molecules of different sizes and see how much of it reaches the fetus.

Before this, I had never done any sort of dissection. I have very little experience with animals and none at all with rats. I gutted a fish once, but it wasn't pretty... Obviously I got quite nervous when I found out I would be using rats... I actually asked my professors if it would be possible to place me in a group which didn't involve blood, but the research team has to divide its work properly in order to provide a good picture of the different transporter pathways, so everyone is sitting on a piece of the puzzle... so I wasn't too happy about my allotted piece, but I decided to do it for the team hehe.

Alright now.. to some, this might be troublesome to watch. It'll get a little gory if you scroll down, but don't tell me I didn't warn you ;)

One of our most experienced members, Sato-san, posing with the first rat of the semester. The green mat is heated to ca 37 degrees Celsius, to keep the rat warm. The rat is alive and breathing, but has been injected with an anaesthesia. The lamp also helps keep the temperature up, but when we open up the rat it unfortunately also causes the normally wet body tissue to dry.. so we soak it in water (with a little bit of salt, just like the normal body fluids). The rat's limbs are secured with tape, so it doesn't slip. Look at that big smile! She really loves what she does! For mankind! Yeey!

Sato-san skillfully cut up the rat and exposed part of the womb. There was very little blood, but then again it wasn't exactly her first rat... She's the kind of student who comes to the lab even on a holiday, to "practice". We all look up to her :)

Here we see the "left side" of the womb, with fetuses clustered together like a chain of grapes. Small grapes.. made out of meat.

A fetus, taken out of its little "bubble" and placed on a wet paper tissue. Since the mother is in the 18th day of pregnancy (out of approximately 20), the fetus is almost fully developed (although a lot seems to happen during the last day) and it moves a little.. waving it's tiny legs slowly.. kind of creepy, really. What we have attempted here is to insert a catheter into the uterine artery connected to a placenta which in turn is connected to this little guy. We then proceed to insert another catheter in the umbilical artery... but it's extremely difficult as the needle is thicker than the blood vessel. Also, on that tiny scale everything tends to get sort of sticky.. Once in, we have to be careful not to push it in too much and pierce the opposite wall of the vessel. Add to that the fact that artery and vein are right next to eachother and you can imagine how hard it is to know whether or not your needle is in the right place.

We considered this a "practice session" just to get a feel for how to properly handle the blood vessels and surrounding tissue and such.

A young apprentice having a go at the other side of the womb. Lots of fresh fetuses to play with! Pharmacokinetics has never been more fun!

Every Igor has to start small...

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