Wednesday, 22 June 2016

All the Small Things

It’s always interesting/entertaining/amusing when an animal does something we think is typically human; a dog riding a bike, a cat playing Candy Crush, a hamster surfing, and thanks to the internet we can see all these things, what a time to be alive. But the other week I was surprised to hear of an animal that did something no-one thought it could do and the repercussions of this could have a major impact on the world of endometriosis research.

This was a report I read documenting the first ever observed occurrence of a species of mouse (the spiny mouse to be precise) having a menstrual cycle. Up until now the only animals we were familiar with that menstruate were primates like chimps, gorillas and humans. Other animals have different reproductive cycles characterised by different hormonal and physical changes in their reproductive organs. Most other mammals, including mice, undergo an estrous cycle. The estrous cycle, like the menstrual cycle, is still regulated by hormones such as estrogen and progesterone, but the way these hormones vary throughout the respective cycles and the effect they have, differs.

The diagram below shows how the different hormones that regulate the function of the reproductive organs changes over the human menstrual cycle and the rat estrous cycle. If you want to see how these hormones work in humans I've covered it here.

As you can see, there are quite obvious differences, but also some similarities between the two. The rat proestrus stage for example, is somewhat similar to the human day 14 and the rat day 4 resembles the human day 10, but overall they are quite distinct. In terms of the actual physical changes, menstrual animals shed their endometrium after each cycle if conception doesn’t occur. This, as some of you will all too painfully know, is having a period. Estrous animals on the other hand reabsorb the endometrium if conception doesn’t occur and, although some animals like dogs might bleed at certain times of their cycle, this is not an actual period, rather it is caused by estrogen making the blood vessels in the vagina ‘leaky’.

So the discovery of a menstrual cycle in the spiny mouse is surprising to say the least, but why is this relevant to endometriosis research? In order to study the way in which endometriosis works and develop new treatments we can grow endometriosis cells in the lab and experiment on them. Unfortunately this tells us nothing of the complexity of the disease or how endometriosis behaves in a living organism. For this researchers turn to animal models of the disease. This is usually achieved by ‘inducing’ endometriosis in a lab animal (typically estrous mice). However this is far from a perfect model of the disease. Inducing the disease in mice is achieved by transplanting either pieces of whole uterus, or pieces of the normal endometrium into the pelvis of the mice. Neither of these gives a true representation of human endometriosis, but it’s the closest thing researchers have at their disposal to study endometriosis (there are much more accurate primate models of endometriosis, but there are numerous reasons, such as cost, facilities and ethics, that prohibit the use of these animals in most research centres).

Another problem is that because normally mice don’t menstruate, the disease will not behave in mice the same way it behaves in humans due to different levels of hormones in the body. Mice can be made to have hormonal cycles like humans but this involves removing the ovaries and supplementing them with hormones and even this doesn’t represent the complexity of hormonal changes during the human cycle.

By using an animal that can menstruate, our models of endometriosis would become more accurate (in fact we may not need to induce endometriosis in these spiny mice if they develop it spontaneously, much more investigation is needed to observe this though). By extension the way we understand the disease in humans and the effectiveness with which we can develop new treatments will also become more accurate. Additionally, one of the goals that researchers work towards is reducing the number of animal experiments that are required to study any given disease. By using an animal that more closely resembles the human menstrual cycle, it would eliminate the need for performing additional procedures on lab mice to induce human-like hormonal cycles.

However, there is still a lot of work to find out exactly how similar the spiny mouse menstrual cycle is to the human one. The initial research that has been done has shown the spiny mouse cycle to be 9 days long. The human cycle is, on average, 28 days long and, interestingly, the pattern of progesterone levels in the blood across the spiny mouse cycle almost exactly matches that of the human cycle.

Although there is a lot of work still to be done investigating this unusual phenomenon, it not only has impact for endometriosis research, but also into other female reproductive conditions, like infertility, pregnancy and menstrual disorders. 


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