Beyond Primates, Rabbits and Mice

Golden Retriever stick its tongue out

 Mammalswithnaturalendometriosis  (Link to summary of three case studies)

Mammals whom are not regular laboratory specimens demonstrate the natural presence of endometriosis.

Recognition that primate females are structurally similar, and experience back-flow of endometrial debri like human females, they are used to investigate the disease.  In fact, up to 25% of Rhesus Macaque in captivity experience endometriosis (1). This is significantly higher than estimates in the wild. It is speculated that stresses involved with captivity may play a role at altering the normal immune response (1).

Numerous studies of primates have reported the presence of extra-pelvic disease in the thoracic cavity without diaphragmatic defects (1). Histological data collected during necropsy inferred  endometriosis was the result of local transformation of lung tissue into active endometriosis lesions (2). Neither of these studies can be explained by the most universally proposed theory of Sampson’s retrograde menstruation.

What if retrograde menstruation is simply a NORMAL physiological process of both species and has NOTHING to do with the development of endometriosis? But, to play devils advocate, micro-metastasis of endometriosis cells to the lungs, spleen, liver and brain among mice with ‘induced’ endometriosis lesions in the abdominopelvic cavity (3).  Maybe its time to  investigation alternate theories of origin.

Mice. Mice do not menstruate. However, mice are easy to manage in a laboratory.  It is important to note is that endometriosis is not a natural occurring pathology (that we are aware of) within mice. For research purposes, endometriosis lesions are ‘induced’ into mice used for laboratory studies.  Where does the ‘induced’ lesions come from?  Extracted uterus tissue.  It is important to understand the first-order ‘bias’ that may occur with this model.  The use of endometrium from the uterus assumes endometriosis lesions are the SAME (or FROM) the uterus.  This implies retrograde menstruation is the origin of endometriosis.  It also gives perception that this tissue undergoes changes (mechanism unknown) which lead to lesions which are ‘similar’ to those of the uterus.  How does this impact effectiveness of medical treatments if lesions are not, in-fact, or uterus origin?  Is this a potential factor to incomplete effectiveness of medical treatments and lack of documented shrinkage/resolution of disease?  What about bone marrow stem cells and hematologic distribution?

Investigation into alternate theories of origin has been limited. Studies which previously  investigated alternate theories have oft been strongly supported by their data.  Unfortunately, independently funded studies are limited.  Most often studies are completed through funding of other parties with a stake in endometriosis. Sometimes funding is received through government or non-profit organizations but most often private organizations, to include the pharmaceutical industry. As a result, other parties influence what studies are funded and the tangible information extracted and potential application.

We recall a study from 1940 (4). Endometrial cells were injected into the ear veins of twelve (12) rabbits Approximately 10 weeks later, necropsy revealed 8/12 rabbits had endometrial glands and/or stroma present in the lung tissue indicating potential hematologic spread of disease.  This differs from the theory of micro-metastasis from induced lesions found in mice mentioned above (3).

Other mammals exhibit natural occurring endometriosis.  Like mice, these animals differ from humans and primates.  They are anestrus.  A regular, cyclical hormone fluctuation with shedding of the endometrial lining of the uterus does not occur among these animals.  Therefore, these animals do not experience retrograde menstruation.  Summary details of three cases reports can be accessed here:    Mammalswithnaturalendometriosis (link).  To access full articles of each case study, select the links below:

1.) 11 yo female German Shepard   https://actavetscand.biomedcentral.com/articles/10.1186/s13028-015-0123-1

2.) 4 yo female Golden Retriever

http://ijvr.shirazu.ac.ir/article_4033.html

3.) 2 yo female Guinea Pig

https://doi.org/10.1155/2017/4594510

As we encourage collaboration among our surgical specialties to address all disease found in the body and encourage multidisciplinary teamwork with primary care, physical therapy, nutritionists, social workers and mental health workers etc., maybe its time to reach out to the veterinary schools, animal husbandry and other animal care services across the spectrum of zoo’s, veterinary clinics, refuges and sanctuaries to study the disease in animals without a menstrual cycle. This removes the variable of regular estrus cycles to examine other pathological processes which may contribute to the formation of the disease.

Citation List: Beyond Primates, Rabbit and Mice     ReferencesBeyondPrimatesRabbitsMice

 

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