ASRM2010: Lessons from a primate model

Denver, 27 October 2010

Professor Asgerally (Asgi) Fazleabas, from Michigan State University in the USA, delivered the exchange lecture on behalf of the Society for the Study of Reproduction this afternoon, focusing on the viability of various non-human primates as models to improve our understanding of endometriosis.

ASRM Scientific Director, Dr Andrew LaBarbera with Professor Asgi Fazleabas at the ASRM, October 2010

As an introduction, Professor Fazleabas made it very clear that the complex aetiology of endometriosis coupled with the extended period of time for diagnosis, limits our understanding of the processes that contribute to the initial development of the lesions and their impact on uterine function.

For example, we know that endometriosis has probably been present in the woman for an extended time before she is diagnosed, and treated, but we do not know for how long – and to what extent the disease is “progressive” during this time. In fact, the mechanisms involving “spontaneous development” are uncertain, as is any association with infertility.

Furthermore, conducting clinical studies, with appropriate controls, is really difficult in endometriosis, because it is difficult to offer women – who are in pain, or infertile – the option (risk) of not receiving treatment if they participate in a placebo-controlled study.

This is where non-human primates come in. Using animals, such as baboons, which develop endometriosis spontaneously, and whose anatomy and physiology are similar to humans, provides an opportunity to understand the fundamental basis of the disease. It may also lead to possibilities for developing diagnostic methods and testing treatment efficacies. This is not possible in other models, such as rodents, because – since they do not menstruate – spontaneous development cannot be evaluated, and nor can infertility, because these models are typically hormonally compromised (ie. they are treated with oestrogen to feed any endometriotic lesions that are implanted into the model).

Primates, however, can be studied from the beginning of them having endometriosis and also over time. Over the past decade fundamental studies in a baboon model of endometriosis have suggested that as early as one month following the induction of the disease, the peritoneal lesions that are actively remodeling have a profound impact on the eutopic endometrium.

This is manifested by the increased expression of proteins that would facilitate adhesion and invasion of menstrual tissues on the peritoneal surface and early changes in the eutopic (endometrial cavity) that reflect an “oestrogenised” state. As the disease progresses, “progesterone resistance” develop and the uterus becomes less conducive to successful embryo development.

Progesterone resistance has become a well-accepted principal of the human disease condition and work in the baboon suggests that this is a progressive response to the continued presence of endometriotic lesions. Furthermore, this resistance also impacts on the ability of the uterine endometrium to respond to signals from the early embryo which can have a profound negative impact on the establishment of pregnancy.

Professor Fazleabas is presented with the exchange lecture certificate by Professor David Adamson, a former president of the ASRM

In summary, the baboon model of induced endometriosis provides substantial clues to the mechanisms associated with the early establishment of the disease and its impact on fertility.

Such findings may enable the development of diagnostic tests (such as a biomarker) and perhaps identify genetic traits.

One limitation in using any non-human primate model, however, is the fact that whereas animals may be in pain, and show pain, we have no way of measuring the intensity of this and thus evaluate the effect that various treatments have on their symptoms.