Overload
of iron in the pelvic cavity may promote proliferation
of endometriosis lesions' epithelial cells
Research on mice, published in Human Reproduction,
has led a team from the Catholic University of Louvain
to conclude that an overload of iron in the pelvic cavity,
while not causing the condition, may make the lesions
grow by promoting the proliferation of their epithelial
(lining) cells.
Belgian fertility experts believe this may be a step
forward in finding the answer to endometriosis. They
hope that their findings may lead to better treatment
for women, possibly in the next five years.
They have found that treatment with an iron chelater
- molecules that bind tightly to metal ions and neutralise
their damaging effects on the body - can reduce cell
proliferation in the lesions.
Iron deposits are typical features of endometrial lesions
and increased concentrations are found in the pelvic
cavity of patients with the disease. The researchers,
led by Professor Jacques Donnez, head of the Department
of Gynaecology, hypothesised that iron overload might
be involved in the origin and development of endometriosis.
The iron could originate from the breakdown of erythrocytes
(oxygen-bearing red blood cells) carried into the pelvic
cavity by retrograde menstruation (menstrual blood flowing
back into the fallopian tubes).
To test their hypothesis they induced endometriosis
in a nude mouse model (mice without immune systems)
by injecting human menstrual endometrium into:
- one control mouse, which had only the injection
of endometrium;
- one mouse which had an injection of endometrium
plus human erythrocytes;
- one mouse which had an injection of endometrium
plus an iron chelator - desferrioxamine (DFO).
The experiment was replicated eight times (24 mice).
A total of 78 lesions were collected from 22 surviving
mice out of the 24, with no statistically significant
difference in the number or surface area of lesions
in the three groups.
But there was a significant difference between the
groups in the amount of iron and the level of macrophages
(scavenger cells that surround and kill micro-organisms,
remove dead cells and stimulate immune cells).
Said Professor Donnez: "Cell proliferation in
the epithelial glands in the lesions and iron load in
the pelvis was markedly greater in mice injected with
erythrocytes than in control mice, with the overload
in the tissue and pelvic cavity being similar in nature
to that found in the pelvic cavity of endometriosis
patients. There was also a significant increase in the
percentage of iron-loaded macrophages compared with
the control group. By contrast, iron levels in the DFO-treated
mice were similar to the control mice, and cell proliferation
was lower than in the control group.
What this clearly suggests is that peritoneal iron
overload in patients may well originate from the breakdown
of the red blood cells involved in retrograde menstruation.
Activated macrophages probably play an important role
in degradation of these red blood cells and the resulting
peritoneal iron overload could have numerous cytotoxic
effects in the peritoneal area."
Professor Donnez said the DFO treatment decreased significantly
the number of lesions containing iron deposits, the
iron concentrations in the peritoneal fluid and the
percentage of iron-loaded pelvic macrophages.
"An iron chelator could thus be beneficial in
endometriosis to reduce the iron content of the peritoneal
cavity, moderate its deleterious effects and reduce
the cellular proliferation of lesions. Our findings
represent a crucial step in finding the answer to endometriosis
because we are focusing our research more on the origins
and causes of the disease in the context of prevention,
than on surgical treatment when the disease is already
present. We really hope that, in the future, genetics
will help us to determine the population of young women
at high risk of endometriosis and that treatment, resulting
from our findings, may then prevent the development
or evolution of the disease."
He said it was vital that endometriosis is taken seriously.
It affects millions of women in their reproductive years
and its prevalence appears to be increasing. "It
is a disorder that causes a lot of pain and distress
to women and has far-reaching socio-economic implications."
The researchers have now received a major grant from
the Région Wallonne research department in Belgium
for further animal trials.
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