New mouse model 'opens doors to better understanding of endometriosis'
Approximately 176 million women and girls worldwide have endometriosis. But regardless of its widespread occurrence, there is still little known about what causes the condition. Now, researchers have created a mouse model of endometriosis that they say will provide a better understanding of its development and may lead to improved treatment.
This is according to a study recently published in The American Journal of Pathology.
Endometriosis is a condition in which tissue that normally lines the uterus grows as lesions on other areas, such as the bladder, bowel and ovaries. Symptoms of the condition include chronic pelvic pain, painful menstruation, irregular vaginal or uterine bleeding, large, painful ovarian cysts (known as endometriomas), rectal pain, chronic fatigue and infertility.
The condition is most common among women in their 30s and 40s but can occur among any female who has menstrual periods.
It is unknown as to exactly what causes endometriosis, but past studies have suggested it could be due to a faulty immune system, overproduction of the hormone estrogen or a result of tissue that has not been removed during a woman's monthly period.
According to the research team, led by Dr. Erin Greaves of the MRC Centre for Reproductive Health at the University of Edinburgh in the UK, research in the field of endometriosis has been hindered by lack of a suitable animal model in which to study the condition.
Use of nonhuman primates - such as monkeys - has been restricted by cost and ethical worries, the researchers say. Although rat and mouse models are lower cost and smaller in size, they pose many disadvantages.
The researchers explain that mice do not naturally menstruate, therefore scientists often have to suture tissue on their pelvic organs, meaning the tissue may not mimic natural conditions or immune responses.
Menstruation induced in mice to create model of endometriosis
In order to tackle this problem, the team decided to create a mouse model of endometriosis that uses naturally produced menstrual tissue.
To do this, the researchers induced menstruation in a donor mouse using the hormones estrogen and progesterone. The tissue the mouse shed from its uterus was then removed and implanted into a recipient mouse.
After this tissue grew on the recipient mouse - just as it would in a human with endometriosis - it was removed and analyzed by the researchers.
Explaining what the team found from their analysis, Dr. Greaves says:
"We found that lesions recovered from a variety of sites in the peritoneum of the mice shared histologic similarities with human lesions, including the presence of hemosiderin, cytokeratin-positive epithelial cells, vimentin-positive stromal cells, and a well-developed vasculature. Most of the lesions had evidence of well-organized stromal and glandular structures."
Macrophages in shed endometrium 'contribute to development of lesions'
The team then conducted experiments using donor mice that had green fluorescent protein-labeled macrophages - immune system cells that ingest foreign bacteria - in their endometrial tissue.
The researchers hope their newly created mouse model of endometriosis will advance research in the field and lead to a better understanding of the condition.
After transferring and growing this endometrial tissue in recipient wild mice, the team discovered that the macrophages in the tissue survive and create a "pro-inflammatory microenvironment" that plays a role in the development of endometriotic lesions.
"We are excited by these findings because the contribution of macrophages present in shed endometrium to the etiology of endometriotic lesions has not been studied in previous mouse models," says Dr. Greaves.
The team says they hope their newly created mouse model will assist future studies investigating endometriosis and lead to a better understanding of the condition, as well as help identify new targets for treatment.
Earlier this year, a study by researchers from the Massachusetts Institute of Technology uncovered cellular activity that may lead to a better understanding of endometriosis.
A recent spotlight feature by Medical News Today also investigated how diagnosis for endometriosis can be improved.
Written by Honor Whiteman
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