Tuesday, 17 February 2015

Since first it was my fate to know thee

Just a quick update to highlight a case report I find particularly important when considering the origin of endometriosis. This case report from the US is of a pregnant woman who, after a scan at 35 weeks, was told that her unborn child had a large abdominal mass measuring roughly 6.5 x 4.8cm, a mass which there was no sign of at the 20 week scan. A further scan at 37 weeks revealed that the mass, which had all the hallmarks of a large cyst, had grown to 7.8 x 6.8cm. No doubt fearing for the health of both mother and unborn child, the decision was made to induce the pregnancy at 38 weeks. After delivery the infant was operated on, the cyst removed and was otherwise perfectly healthy.

Analysis of the cyst revealed the tell-tale signs of an ovarian endometriotic cyst i.e. a thin walled cyst filled with reddish-brown fluid, which the pathologist later confirmed. Ovarian cysts in unborn females foetuses are not unheard of, but are extremely rare and endometriotic cysts even rarer, in fact this is the first case I’ve seen reported.

I have though, seen reports on microscopic endometriosis being found unborn female foetuses and talked about them here. However, these findings usually describe very small areas of endometriosis, hardly what you could call ‘mature’ disease. This most recent case is particularly unusual then as it represents what’s is termed ‘advanced’ stage endometriosis (although in reality there is some contention as to whether endometriosis is a progressive disease and therefore whether words like ‘early’ and ‘advanced’ stage endometriosis are even relevant). Certainly this case casts doubt on the assumed notion that endometriosis progresses to further stages as you get older.

Furthermore, this raises more questions about the origin of endometriosis. The accumulating evidence suggests that endometriosis is a dormant developmental disorder; something with which you are born that becomes active around the time of puberty. How, when and why the symptoms associated with endo come into being is another matter altogether. How endometriosis arises during development is another big question. Displacement of stem cells? Abnormal growth of portions of the reproductive organs? Early menstrual influences before birth? Yes, you read that last part right. The uterus of new-born females is capable of undergoing something akin to menstrual changes and menstruation. Of the very few studies that have looked into this, the general finding was that visible bleeding was observed in around 5% of new-born females, caused by exposure to, and withdrawal from, the mothers hormones. This may lead to a sort of prenatal retrograde menstruation of endometrial cells, planting the seeds of endometriosis in the pelvis before birth. Of course, there are still many stumbling blocks to overcome before any theory on the origin of endometriosis is widely accepted, some of which I’ve touched upon previously

Title from Thomas Hardy’s poem ‘How Great my Grief’

Monday, 9 February 2015

What am I doing?

“What am I doing?” A question I usually ask myself in a moment of crushing self-realisation after drinking a not insignificant amount of a famous brand of bourbon and embarrassing myself in front of my peers on a night out.  

But in this instance, the question ‘what am I doing?’ refers to the subject matter of my research. I’ve been doing my PhD for just over a year now and have only recently found my stride with it. Scientific research can be a perplexing venture; I’ve changed focus more times than I care to count. Of course a big part of that is my own tendency to pursue new avenues of interest like a dog being thrown a bucket of tennis balls. My main interest has and always will be endometriosis and working at this university has given me lots of opportunities (too many opportunities actually, not that that’s a bad thing) to investigate endo in different ways. Every new idea I have, there are the facilities here to investigate it, like being a kid in a candy store, but instead of candy store it’s a vast scientific research institute.

But anyway, enough of that rambling, I was talking about being focussed. My research is examining the role that fatty acids play in regulating inflammation in endometriosis. ‘Fatty acids’ is a bit of a vague term so I’ll clarify that first. You’ve probably heard of Omega-6 and Omega-3 polyunsaturated fatty acids; different foodstuffs like to advertise that they are ‘rich in Omega-3s’ or something along those lines. These include essential fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which fall under the Omega-3 category. Then there is arachidonic acid and linoleic acid which fall under the Omega-6 category.

We get a lot of these fatty acids from our food, but it’s what our body does with them that’s important.  When our body takes in these fatty acids, they are incorporated into the outer layer of our cells (the cell membrane) which acts as a storage space for them. The stored fatty acids can then be release from the membrane and converted into a whole plethora of different products by different enzymes, which can serve a whole manner of different functions (below is a diagram that summarises the process). In one sense this is why maintaining a healthy diet is important, it means you get the right balance of these fatty acids. From the other perspective, it may not matter how good your diet is, because your body (or certain parts of it) may not process the fatty acids correctly due to the presence/absence of certain enzymes or receptors for these fatty acids.

One function regulated by the products of omega-6 and omega-3 fatty acids is inflammation, which is very important when talking about endometriosis. Your body treats endometriosis very much like a wound, but a wound it can’t heal, so it releases a number of chemicals which ramp up the inflammatory response near the disease. Some of the products of fatty acid metabolism are key players in regulating this inflammatory response. In addition, this rogue inflammation is thought to contribute to the severe pain symptoms with which so many women with endo suffer.

You’ll notice that one of the products of Omega-6 fatty acids, the 2 series prostaglandins, are highlighted in red. This is because they are the only group of fatty acid products that we know the function of in the reproductive system in any great detail. There are numerous members of the series 2 prostaglandin family, but I’ve selected prostaglandin E2 (PGE2) and F2 alpha (PGF2a) as they are known to produce a strong inflammatory response. All of the others (don’t worry what the acronyms stand for, we’ll be drowning in syllables if I put the full names in) we don’t have any idea what roles they play, if any, in the normal function of the female reproductive system and what the consequences would be if they went awry.  

So the first part of my research is to investigate which of these fatty acid products are present in the endometrium. This is actually pretty exciting because it means making genuine discoveries. As I mentioned above we don’t know which of these fatty acid products are present in the endometrium, so discovering that will be something no-one has ever done before, exactly the type of thing us science geeks get excited about.

The second part will be to find out what differences there are, if any, in the fatty acid products from the endometrium of women with and women without endometriosis. Hopefully, finding fatty acids that are either much higher or much lower amounts in endometriosis patients will give some indication as to which of them are important. Because we don’t really know what these fatty acid products do in the uterus there’s no telling how important they may be; they might control inflammation, they might be important for hormone regulation, they may even be involved in fertility, or they may just be inconsequential. No matter what the outcome that is pretty much what I’m doing and hopefully it will lead to discoveries that will help us better understand (and better treat) the symptoms of endometriosis.