Projects

Developmental, Reproductive and Metabolic effects of Endocrine Disruptors: the DReaM-ED study
2022-2025 | PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE (PRIN 2020)

Stefano Gotti, head of research unit
Research network: coordinator Angela Di Baldassarre, Università degli Studi "G. d'Annunzio" Chieti-Pescara

Endocrine disruptors (EDs) are compounds that have the ability to affect the endocrine system by interfering with the hormone synthesis, bioavailability, and action, thereby altering cellular proliferation and differentiation, tissue development, and several metabolic processes. Among the main EDs, bisphenol A (BPA) and perfluoroalkyl compounds (PFAS) have undergone a widespread diffusion worldwide in recent decades. The aim of this project is to evaluate the effects of the current daily human exposure to single or combined EDs (PFOS and BPA) during the highly sensitive prenatal developmental stages. Combining animal and cellular-based models, we will analyze the molecular mechanisms by which exposure to EDs can alter perinatal stem cells, organ development, the reproductive capacity, the neuroendocrine axis, and the neurobiological and behavioral characteristics, taking into account possible sex-specific effects.

SARS-CoV-2 and more: bringing a pan-coronavirus antiviral drug candidate up to human experimentation ( SILK). Thinking innovative to fight the unexpected
2021-2023 | Finpiemonte S.p.A – INFRA-P2

Stefano Gotti, head of research unit
Research network: coordinator Marco Lucio Lolli, Università degli Studi di Torino

The new disease COVID-19 has found our society largely unprepared to deal with a pandemic event of this magnitude. The pandemic is teaching us that even with the availability of effective vaccines, viral evolution can lead to the spread of variants that escape the neutralizing response induced by vaccines. Therefore, there is an urgent need to discover molecules capable of inhibiting cellular mechanisms essential for the completion of the replication cycle of all coronaviruses. This project aims to bring an innovative antiviral drug developed within UniTo to the threshold of human experimentation. We have solid preliminary in vitro data and we are analyzing pharmacokinetics and toxicity in animal models.

Maternal separation in Anorexia Nervosa: possible role of Oxytocin - study on the ABA animal model
2021-2023 | Fondazione Cassa di Risparmio di Torino (CRT)

Stefano Gotti, head of research

We want to study the effects of maternal separation (MS) on the Oxytocin (OXT) system in an animal model for Anorexia Nervosa (AN). AN, an eating disorder with a complex etiology, affects women more frequently and the onset often occurs during adolescence. AN induces physical symptoms such as severe weight loss, as well as behavioral and cognitive dysfunctions. It is known that exposure to negative environments, in the early stages of life, can contribute to the subsequent development of psychoneuroendocrine alterations. In particular, lack of maternal care (attachment) and adverse events at an early age may play a crucial role in the pathogenesis of psychiatric disorders, including eating disorders. OXT is a neuropeptide involved in parental care behaviors and social behavior. Since there are still many ethical problems for human experimentation, this research aims to verify the effects of MS related to the OXT system in animal models with AN.

Soy: a good nutritional supplement in Anorexia Nervosa during pregnancy on the Health of Mothers and Offspring?
2022-2024 | Brain & Behavior Research Foundation

Marilena Marraudino, head of research

Legumes, in particular soy, are particularly abundant in phytoestrogens, such as Genistein (GEN), an endocrine disruptor (IE). Women with eating disorders, mainly those with anorexia nervosa (AN), consume more soy products and plant-based foods. AN is a disease characterized by a restriction of energy intake, resulting in significant weight loss, intense anxiety due to weight gain and distorted perception of weight and body shape associated with perfectionism and excessive control, which generates a high level of stress. Stress and altered maternal mood in pregnancy, consequential to high levels of CRH, could damage the intrauterine environment, entail the risk of adverse obstetric outcomes or affect correct fetal development.

Dependence on new technologies: development of an animal model for future human applications
2019-2021 | Fondazione CRT

GC Panzica, M Marraudino, S Gotti

The objective of this project is to induce an attachment to new technologies ('addicted') in wild type rats (Wistar Kyoto Rat, WKY), through the use of a new equipment, designed and conceived specifically for this purpose, which mimic the dynamism of a video game. It is therefore our intention to compare and correlate brain and behavioral circuits in control rats by comparing them with those of “addicted” to the new technology. Subsequently, we aim to characterize the neuronal circuits and neuropeptides (and neurotransmitters) involved in hyperactive behavior disorders, particularly the oxytocin system. Young and sexually mature animals of the two sexes will be compared, to better characterize the systems under analysis during development and especially in the delicate pubertal phase, in which hyperactivity is often linked to the poor learning ability and interrelation between peers.

Central Hypogonadism, Group NICe
2013 - Permanent Study Group | Italian Society of Endocrinology

Coordinator: Luca Persani, Milano (Italy)

The central hypogonadism (ICe) comprise a family of rare diseases characterized by gonadal failure and infertility secondary to a defect in the hypothalamic-pituitary axis. In congenital forms, altering pituitary-gonadal may be associated with other defects (eg. Olfactory, neurological and kidney) in Kallmann syndrome (SK). Late diagnosis and incorrect therapeutic management of these conditions may cause serious physical and psychosocial negative consequences. 
In addition to the neonatal onset forms, that have a frequency still poorly defined, there are also forms of ICe much more common: the so-called functional or reversible forms that can affect both teenagers and adults subjects with special eating or habits behavior (strenuous exercise, eating disorders) or psycho-physical problems (stress, adoptions, malabsorption, etc.). 
Finally, there are also ICe idiopathic forms with adulthood onset.
These diseases are characterized by a considerable heterogeneity of clinical onset and framework severity that are also reflected in a variability in the response to currently available therapies.
more info >  www.societaitalianadiendocrinologia.it

Involvement of estradiol on feeding neurohormonal circuit programming in the rat
2016-2019 | Spanish Government, Ministry of the Economy

Coordinator: Paloma Collado, UNED Madrid (Spain)

The aim of the present project is to investigate if estradiol during first stage of development participates in the programming/organization of the neurohormonal circuit of food intake as well as in the expression of the feeding behaviour. Moreover, in this project we investigate the estrogen receptor pathway, ERα, ERβ o GPR30, throughtout estradiol exert these effects.

EDCs Endocrine-Disrupting Chemicals Task Force
2015-2017 | Endocrine Society

Coordinator: Jean-Pierre Bourguignon, Liege (Belgium)
Co-chaired by R. Thomas Zoeller, PhD, and Jean-Pierre Bourguignon, MD PhD, the EU EDC Task Force comprises leading endocrinologists from Belgium, France, Germany, Italy, and the United Kingdom. Task Force members are Barbara Demeneix, PhD, DSC; Richard Ivell, PhD; Josef Koehrle, PhD; Adriana Maggi, PhD; GianCarlo Panzica, PhD; and Remy Slama, PhD.

On April 1, 2015, the Endocrine Society convened endocrine experts from key European Union (EU) countries in Brussels, Belgium, to meet with EU policymakers on the issue of endocrine-disrupting chemicals (EDCs). 
As part of a strategic initiative to ensure endocrine principles are incorporated into global EDC regulatory policies, the Endocrine Society established its EU EDC Task Force to inform and advocate with members of the European Parliament (MEPs) and officials within the EU Directorates General in charge of chemicals laws and regulations.
more information >  www.endocrine.org  

COST European Cooperation in Science and Technology
DSDnet - A systematic elucidation of differences of sex development
2013-2016 | EU Framework Programme Horizon 2020

Coordinator: Olaf Hiort, Lubecca (Germany)
The 22 DSDnet Member Countries are: Austria, Belgium, Italy, Israel, Bulgaria, Netherlands, Croatia, Norway, Cyprus, Poland, Denmark, Romania, Estonia, Slovenia, Finland, Spain, France, Sweden, Germany, Switzerland, Hungary, United Kingdom

Differences or Disorders of Sex Development (DSD) constitute a complex group of rare diseases that are caused by chromosomal, genetic and endocrine metabolic disturbances that affect the endocrine-reproductive system, thereby modulating the sexual phenotype of a given person. DSD poses great challenges for our understanding of sex and gender development in biology, medicine and societal issues.
This COST Action will link leading international scientists, clinicians, and stakeholders in the field to characterise DSD with the aim of a diagnosis to all people with DSD with structured, potentially personalised, management and therapies. The Action will aid to the understanding of the clinical heterogeneity as well as reveal the pathophysiological commonalities between different forms of DSD at the molecular level. It will additionally benefit the science in rare diseases of the international community and also the formation of a European Reference Network.
more information >  wwww.cost.eu | www.dsdnet.ue

COST - European Cooperation in Science and Technology
GnRH NETWORK - Neuroendocrine Control of Reproduction
2012-2016 | EU Framework Programme Horizon 2020

Coordinator: Ulrich Boehm, Homburg (Germany)
GNRH Network: Belgium, Italy, France, New Zealand, Switzerland, Hungary, United Kingdom, Finland, Romania

This grant is devoted to developing an international network of clinicians and investigators in the fields of reproductive medicine and neuroscience. Specifically we aim to explore the causes of GnRH deficiency, including Kallmann syndrome.  Broadly, this project is intended to foster new collaborative relationships, attract and develop young investigators in the field, accelerate the pace of scientific discovery, educate patients and translate these findings to improved patient care.
Our group is involved in working group 3 Basic Science
Specific Aims
The focus of Basic Science Working Group (WG3) is to bring together leading European experts in the field of neuroendocrine control of reproduction.
• Develop an interactome of basic expertise among Action members
• Lead creation of a European Reproductive Animal Model Clinic
• Help prioritize candidate genes identified through whole exome sequencing based on expression studies, cellular studies, and in silico analyses
• Identify biologically plausible candidate genes for GnRH deficiency through studies in model systems which will then be tested for mutations in the patients' DNA samples by the Genetics and Bioinformatics Working Group (WG2)
• Characterise the roles of novel disease genes in the neuroendocrine control of reproduction thus providing both validation and mechanistic insight
more information > www.gnrhnetwork.eu