Endometriosis Awareness Month 2013 – Part IV

Rapidly continuing our voyage into endometriosis research over recent times we find ourselves in familiar territory. I’ve always had an inkling that endometriosis is a condition women are born with, but without a body of evidence to support it, it would remain just an hunch. However, over the years I’ve been writing this blog there has been a noticeable growth in evidence supporting the notion that the decision as to whether a woman will, or will not development endometriosis, is made before she is born.

Recently another paper has been published from the research group that identified displaced endometrial tissue, characteristic of endometriosis, in human foetuses. Although this time the researchers were looking at genetic differences between normal endometrial tissue and endometriotic tissue. What they found was that two genes of particular interest were altered in the endometriotic tissue, namely BMP4 and GREM1. What makes these genes so interesting is that both appear to be involved in Müllerian duct differentiation. I’ve talked before about the Müllerian duct and how it is basically the precursor to the female reproductive system during foetal development. The process of differentiation is when cells become specialised to carry out a certain function within the body.  We all started off as a single cell, but in order to become the complex organisms we are, as our cells divided they had to acquire specialisations. So during the development of a female foetus, the Müllerian duct begins to differentiate into the specialised tissue types (such as endometrium, myometrium etc) it eventually becomes in an adult. What this piece of research highlights is that it appears as if, by some as yet unknown mechanism, endometriotic tissue arises because of an error in cellular differentiation during the formation of the female reproductive system long before you are even born.

Continuing along a similar line is the next paper which examines what happened to mice whose mothers have been exposed to hormonal manipulation whilst they were pregnant. This study took pregnant mice and exposed them to a compound called ethinyl estradiol during days 11 to 17 of their pregnancy. Ethinyl estradiol (EE) is a synthetic version of the human form of estrogen; it’s most often used in hormone replacement therapy (HRT) or in combination with a progestin in contraceptive pills. After the mice were born they were kept up to the age of 28 weeks old then killed and their reproductive organs examined. What the investigators found was that mice exposed to EE prenatally developed a far greater number of endometriosis like lesions on their ovaries and adenomyosis was also found to be far more obvious in the uteri of exposed animals.

It’s interesting to note that the authors didn’t record any endometriotic lesions in any other locations apart from the ovaries in these exposed mice. In last week’s post I mentioned a piece of research that subtlety hinted ovarian and peritoneal endometriosis may have different origins and this study also hints at the same possibility (Although, if you want more than just hints, there have been whole reviews dedicated to the difference between the different types of endometriosis, by authors far more knowledgeable than myself).

Of course when considering this latest study we must take several things into consideration. Most importantly that this was a study using mice and although mice make good models for investigating human disease they can never be considered perfect, especially when looking at reproductive conditions. If we look at the difference between the female reproductive system in the mouse and human, not only do they look different, but they function differently as well. Mice, for example, have oestrus cycles (i.e. they can only get pregnant when they are ‘in season’) but humans have menstrual cycles which differ in many ways. Therefore, although this research does certainly gives us pause for thought, we can’t make a leap of suggesting the same hormones will have the same effect in different animals.

Pictured above - not a human (Image courtesy of morgueFile)

 Finally for this week is a study into digestive function after surgery for endometriosis involving the rectum. This study followed 75 women undergoing surgery for deep endometriosis infiltrating the rectum; 24 of whom underwent surgery when more radical methods were in favour, and 51 who underwent surgery when conservative methods were more in vogue. Afterwards each patient was given a number of different questionnaires to assess the health and function of their bowels as well as assessing their overall health, both physical and mental.

This study found that 67% of women undergoing surgery during the radical phase had a colorectal resection (where part of the bowel is removed), compared to only 20% of women who underwent surgery during the conservative phase. Women who underwent the more conservative surgery mostly had either localised excision of the disease or a procedure delightfully known as rectal shaving (Googling that term gives a number of very interesting, but unrelated results, so I’ll spare you the blushes and just link to a relevant video of rectal shaving of endometriosis actually being performed).

After the results of the various questionnaires had been analysed it was found that women who underwent the conservative surgeries fared much better in terms of digestive function and bowel movements than those who underwent radical surgery. Overall this study shows that the ‘sledgehammer to crack a walnut’ approach to removing colorectal endometriosis is not always in the best interests of the patient and more extensive training in conservative techniques is needed for surgeons treating women with endometriosis.