Italian Endometriosis Foundation
Projects of the Italian Endometriosis Foundation:
Duration: 5 years (2015–2022)
The “GENOME” project studies the morphogenetic role of the estrogens (hormones) and the various data from the scientific literature suggesting that the molecules responsible for the estrogen biosynthesis and metabolism are involved in the endometriosis development as well. The project is focused on the characterization of genetic polymorphisms in genes coding for proteins involved in such mechanisms. The main subject of this research is the family of proteins coding for the principal enzymes of the estrogen biosynthesis.
Defining the genetic alterations responsible for endometriosis predisposition has different potential benefits and consequences. First of all, it should allow the identification of patients that risk developing the disease during the prepubertal phase. Moreover, it could contribute to a better definition of the molecular mechanisms that cause the onset of this pathological phenotype and, thus, serve as the rational basis to design specific therapeutic molecules for endometriosis.
Duration: 5 years (2016–2022)
This project aims to define the anatomo-clinical picture of this disease in the most detailed way possible by implementing the collection of parameters (up to a million) about endometriosis patients and using the large database of the Italian Endometriosis Foundation, which has already registered over 320,000 parameters.
The correct definition of the anatomo-clinical picture of endometriosis, especially in relation to the clinical outcomes of various therapeutic procedures, has different potential benefits and consequences. First, thanks to the possibility of predicting the clinical response based on the retrospective analysis data, it could allow the identification of the patients more suitable for certain therapeutic strategies. Besides, it could help a better identification of the most important anatomo-clinical features for the definition of the disease extent and the proposal of novel diagnosis and prognosis classifying schemes.
Duration: 5 years (2016–2022)
This project aims to examine in depth the proper nutrition rules for women suffering from endometriosis and make the diet, developed for the first time by the Italian Endometriosis Foundation on a scientific basis, an actual nutrition programme, in order to provide a suitable science-based nutrition path and protect the health of the endometriosis patients.
This programme should serve as a lifestyle, with the ultimate goal of strongly mitigating the endometriosis symptoms without the use of hormonal, painkiller and/or anti-inflammatory drugs. For the first time, the objective is to make nutrition a treatment for the endometriosis symptoms, based on the new results achieved through the scientific research conducted for years by the Italian Endometriosis Foundation.
Research of the Italian Endometriosis Foundation:
Research activities conducted by the Italian Endometriosis Foundation
Discovery of the endometriosis origin.
Discovery of the endometriosis origin. Study on human fetuses, with the finding of endometrial cells out of place, indicating the congenital origin of the disease.
Study on endometriosis and bisphenol A.
Study on an animal model (BALB/c mice). After administering a pollutant (bisphenol A) to pregnant mice, these gave birth to offsprings affected by endometriosis, leading to the discovery of the cause (pollutants) of the embryonal alteration responsible for the dislocation of the endometrial cells (endometriosis).
In vitro endometriosis model.
Creation of an in vitro endometriosis model by using retrovirus-immortalized cell cultures, which allow the testing of the efficacy of diagnostic and therapeutic aids on the endometriosis cells.
Study on endometriosis and ovarian reserve.
Animal model study demonstrating, for the first time, the relation between endometriosis and ovarian reserve; in particular, the latter is often reduced in endometriosis patients, causing fertility issues and/or early menopause.
Comparative genomic study.
Comparative study between the endometrial genome of endometriosis patients and the genome of their endometriosis cells. Identification of 44 genes involved in embryogenesis that are expressed differently in the endometriosis tissues, regardless of the menstrual and hormonal phases, supporting the hypothesis that the endometriosis condition originates from a gene expression remodelling during embryogenesis.
Study on endometriosis cells.
Identification of the activity that induces cellular death in the endometriosis cells (apoptosis) by the anti-müllerian hormone. In vitro, this hormone inhibits the activity of the CYP19 enzyme, which is a key enzyme in the conversion of steroids into estrogens.
- Prof. Pietro Giulio Signorile (Responsible Director)
- Prof. Alfonso Baldi
- Prof. Feliciano Baldi
- Prof. Lucio Quagliuolo
- Dott. Enrico Spugnini
- Dott. Pasquale Mellone
- Dott. Stefania Crispi
- Dott. Maria Rosaria Boccellino
The Italian Endometriosis Foundation originates from the Italian Endometriosis Association and supports the Italian Endometriosis for the translational research on the disease. Through a scientific network with 11 public and private, Italian and foreign institutes, it conducts the endometriosis research with excellent results that directly impact the prevention, diagnosis and treatment of the disease and the associated conditions. This research requires a multidisciplinary approach. Below, some endometriosis research modes presently adopted by the Italian Endometriosis Foundation are schematized.
Cellular and animal models
- Primary cultures of endometriosis cells
- Immortalized primary cultures (telomerase/simian virus 40)
- Autologous models of nude mice
- Heterologous models of nude mice
- Studies on the human tissue
Collection of clinical records: collection of deep endometriosis cases, classified according to the hormonal phenotype, neurogenesi and vascularization.
Cellular expression profile of normal cells
Variation of the cellular expression profile for pathological cells.
Comparison of the gene expression profiles.
Why using animal models?
- Endometriosis is one of the most common gynaecological diseases;
- The mechanisms and causes of this condition are still unclear;
- It is necessary to develop therapies and treatments more effective than those presently available;
- Chorio-allantoic membrane (CAM);
- Murine models (mice and rats);
|CHORIO-ALLANTOIC MEMBRANE||It can be considered an animal model in a broad sense. It includes an implant of endometriosis tissue in the basal layer of the CAM of chicken eggs fertilised on the 7th–10th day of incubation. It allows the study on the angiogenesis of the endometriosis lesions (Nap et al., 2005, Fertility and Sterility). It enables the evaluation of the invasive potential mediated by metalloprotease in endometriosis (Wolber et al., 2003. Reproductive BioMedicine Online).|
- Fragments of murine uterine tissue have been removed and then surgically transplanted in toto in ectopic sites inside the abdominal cavity of mice and rats.
- The rats developed endometriosis cysts that remained stable for at least 10 months.
- The mice developed endometriosis lesions more similar to those observed in human subjects; these lesions were often multiple and with an intense vascularization.
- Fragments of human endometrial tissue have been surgically transplanted in subcutaneous sites or inside the abdominal cavity of immunodeficient mice (nude or severe combined immunodeficient).
- These fragments originated endometriosis-like lesions very similar, from a macroscopic and histopathological viewpoint, to those of human patients suffering from the disease (Defrère et al., 2006, Human Reproduction).
|Examples of HETEROLOGOUS transplants|
|Fragments of uterine tissue have been removed and then surgically transplanted in toto in ectopic sites inside the abdominal cavity of female rabbits. After about eight weeks, cystic lesions of approximately 1.5 cm were observed. This approach is adopted mainly for imaging studies.|
|Baboons serve as the principal model. Fragments of endometrial tissue are sampled during the menstrual period and transplanted in peritoneal sites.|
Current lines of research
- Creation of autologous and heterologous murine models, with the definition of the preliminary characteristics.
- Evaluation of the possibility of a gene therapy based on a subcutaneous model.
- Evaluation of loco-regional therapies combined in surgical ablation.
- Studies on the endometriosis induction via exposure to contaminants that alter the endocrine pathway of feminizing hormones.
- Studies on murine fetuses to evaluate the alterations of the organogenesis of the female genital apparatus and the possible presence of endometriosis tissue.