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Environmental pollutants found incrusted in iron in endometriotic lesions


Scientists led by Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), the Italian Research Hospital Burlo Garofolo in Trieste show that iron presence in endometriosis is associated to the accumulation of environmental metals, supporting the idea that the environment exposure to toxic chemicals plays a role in the disease.

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Around 1 in 10 women in reproductive age around the world live with endometriosis, an inflammatory disease caused when tissue similar to the lining of the uterus grows outside the womb, such as in the ovaries and fallopian tubes. This causes pain and, in many cases, infertility. Even if women have always been affected by endometriosis, it is only since recently that the scientific community has started looking into it. 

The factors that may lead to endometriosis go from genetic predisposition to autoimmune diseases and environmental triggers. Now a team from Institute for Maternal and Child health IRCCS Burlo Garofolo in Trieste (Italy) has found the presence of iron clustered with environmental metals, such as lead, aluminium or titanium, using beamlines ID21 and id16B at the ESRF.

The accumulation of iron in endometriosis was already well documented. Iron deposits are common in endometrial lesions, indicating an altered iron metabolism. “We knew that iron can create oxidative stress and hence, inflammation, as it does in other conditions, such as asbestosis, so we wanted to know more about what chemical form it takes, how it is distributed and whether there are other environmental pollutants with it”, explains Lorella Pascolo, leader of the study. 

Pascolo and her team came to the ESRF to compare iron nanoaggregates in endometrial lesions of patients with normal endometrium samples of the same patients. “The ESRF beamlines are exceptional instruments to get a clear picture of the role of iron and how it transforms into endometrial lesions”, explains Pascolo. 

They used X-ray fluorescence (XRF) on beamline ID21 to track the presence and distribution of iron and environmental pollutants, and ID16B to fine-tune the findings and reveal additional heavy metals at the nano level. They also used X-ray spectroscopy to reveal the chemical state of the iron. 

Through the XRF analysis, they observed that, when endometriosis affects the ovaries, excess iron is not only close to endometrial cysts, but it also spreads in other areas of the ovarian tissue. These iron deposits reach concentrations of 10–20 % p/p in multiple microspots. 

In the areas where the iron concentration is higher, the scientists detected lead, aluminium, titanium, bromine, chromium, silicon and rubidium. Some of these metals are known as metalloestrogens, which mimic the effects of estrogen and can bind to estrogen receptors and activate them, leading to estrogenic effects in the body. “The presence of these toxic elements where the iron is more prevalent suggests these may influence at least the progression of the pathology ”, explains Pascolo.

 “We are still far away from therapeutic interventions”, explains Pascolo, “but we may hypothesize that drugs like iron chelators can reduce the symptoms and manifestations of endometriosis.   ”. 
The next step for the team is to analyse samples from carefully selected patients, in order to correlate with personal exposure histories, genetic and clinical data.

This study is part of a project granted by Italian Ministry of Health (ENDO-2020-23670288).

Pascolo, L. et al, Science of the Total Environment, Volume 864, 15 March 2023, 161028.

Text by Montserrat Capellas Espuny, video by Mark McGee and Montserrat Capellas Espuny.

Top image: Nano X-ray fluorescent mapping performed at beamline ID16B on an endometriotic lesion (dimension 20x43 µm): chromium detected in connection with the nanoaggregates of iron. Credits: Lorella Pascolo.