A Seminal Piece of Work

Remember when you are at school and there would always be rumours and stories going around the playground, like eating popping candy and drinking cola would make your stomach explode. Well it seems like the media’s attempts at reporting scientific news has become the new school playground.

I say this for several reasons, but particularly because of reports I’ve seen online recently concerning a study into the effect of seminal fluid on endometriosis. Seminal fluid is the major component of semen and, if these reports are to be believed then “It is now understood that exposure of the endometrium, which is the inner lining of the uterus, to seminal fluid may contribute to the progression of the endometriosis in women.” That is a direct quote from one web site attempting to give an account of some new research that was published recently and, in typical fashion, they have misquoted the original research, probably didn’t read the original article and relied solely on vox pops and sensationalism.

Let’s go back to the original research then, which was published here and a press release from the university it was conducted at was written here. For some reason the journal in which the research was published is probably the only journal my university doesn’t have a subscription to, so I can’t read the full article. Therefore the comments I’ll make here are based on the abstract for the article.

To start then these researchers are interested in transforming growth factor beta (TGFβ), a chemical messenger in your body that is involved in cell growth and death. I use the word TGFβ as a singular, but it actually refers to a whole family of messengers comprising over 30 members with a variety of different functions. To be more specific then, these researchers found that a deficiency of TGFβ-1 in mice impaired their development of experimentally induced endometriosis, implicating TGFβ-1 as important for the establishment and growth of endo.  Human seminal fluid has a high concentration of TGFβ, therefore the researchers postulated that exposure so seminal fluid may influence the growth of endometriosis.

To test this they took samples of human endometrium, exposed some of the samples to seminal fluid and some to a normal growth solution. They then surgically implanted the endometrial samples in mice and after two weeks noted that the endometrial tissue that had been exposed to seminal fluid had just over a fourfold increase in volume. On the face of it then it would seem that exposure to seminal fluid does increase the growth of endometriotic lesions. However there are several assumptions made in this study that could impact the relevance of the results.

•  It assumes the normal endometrium is the same as endometriosis. Granted the endometrium and endometriosis do look similar, however in recent years it has been discovered that there are hundreds of differences between them. Therefore the way an experimentally induced endometriotic lesion reacts to a stimulus could be very different from the way a human lesion reacts. 

•  I couldn’t find out whether or not the researchers used the endometrium from a woman with or without endometriosis, but this is also a key point. The normal endometrium from women with and without endo differs in a number of aspects. Of particular relevance is the fact that the endometrium of women with endo has a higher level of TGFβ-1 than women without endo. This could mean that endometrial cells from women with endo are more sensitive to TGFβ (but that depends on whether they have the receptors to recognise TGFβ as well). 

•  Animal models are a continuing source of contention. Unfortunately though they are the only way in which complex diseases can be studied in a living system, so until something better comes along we’re stuck with them. The first issue is that the mice used were immunodeficient i.e. their immune systems were dampened down so they wouldn’t reject the implanted endometrium). This could mean that the way in which the endometriotic implant grew in the animal was different to how it would grow in a human. Secondly, mice don’t have the same menstrual cycle as humans, in fact they don’t have a menstrual cycle at all, they have an estrous cycle. Estrogen and progesterone can alter the production of TGFβ-1 by the endometrium so the cyclic variation and the effect of hormone therapies needs to be taken into consideration. 

• Another thing I couldn’t find out is what the dose of seminal fluid they pre-treated the endometrium was before implanting it in the mouse. This is important because we need to know whether it was physiologically relevant i.e. does the dose they used correspond to what would be found in the human body, in particular, how much seminal fluid actually reaches the pelvic cavity after intercourse and could come into contact with endometriosis.

•  The peritoneum (the layer of tissue that surrounds the reproductive organs) secretes TGFβ-1 itself in women with endometriosis leading to an increase in TGFβ-1 in peritoneal fluid from women with endo. Therefore the amount of TGFβ-1 that seminal fluid contributes may be insignificant compared to the amount already produced around the endometriotic lesions by the peritoneum. 

Overall then it is hard to say whether human endometriosis is ever exposed to seminal fluid or if it can influence the growth of endometriosis in humans, certainly I don’t see any evidence to make me believe exposure to seminal fluid causes endometriosis. For some women with endometriosis sex can lead to pain both during and after, but I would think this is down to pressure and torsion put on the pelvic area that is already sensitised due to of endometriosis, rather than exposure to components of semen.  

Whilst there are limitations to this research, it does give us some interesting points to think about. In particular the effect of TGFβ on the normal endometrium, how this differs between women with and without endometriosis and how this could affect fertility. For example, TGFβs are suspected to be involved in the early development of the embryo and their production changes throughout the menstrual cycle. Finding out if these changes are altered in women with and without endo and if this effects the growth and receptivity of the endometrium is definitely worth investigating.