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Doctoral school

PhD in Neuroscience

Logo di PhD in Neuroscience

Chiara Ballan

Contacts

Supervisor

Stefano Gotti

Phd thesis

Developmental, Reproductive and Metabolic effects of Endocrine Disruptors

Endocrine disruptor compounds (EDCs) are “exogenous chemicals, or mixture of chemicals, that can interfere with any aspect of hormone action”. Their interference is based on the ability to alter the organizational process during “critical periods” or have activational effects in adulthood. Specifically, different adverse reproductive outcomes are associated with the exposure to EDCs, including reduced female fecundity, longer time to conception, higher miscarriage rates and decreased sperm motility. There may be hundreds or more environmental chemicals with EDC activity. The present study aims to focus on two particular classes, bisphenols (BPs), perfluoroalkyl organic substances (PFASs) and their possibly interaction, both highly prevalent in daily life. 

First class, specifically bisphenol A (BPA), is used in a very wide array of manufacturing, food packaging, toys, and other applications, and BPA resins are found in the lining of many canned foods and beverages such that virtually everyone is exposed continuously. In food contact materials (FCM), BPA may leach into food or water under high heat, physical manipulation, or repetitive use. The chemical is rapidly metabolized to non-bioactive forms and has a short half-life of approximately 4–5 hours in adult humans, with lower metabolic rates in the fetus and infants. Nevertheless, early pregnancy seems to be a particular sensitive period to BPA exposure, linked to the development of some adverse effects, such as intrauterine growth restriction. In April 2023, the European Food Safety Authority (EFSA) published a new evaluation of the safety of BPA, significantly reducing the tolerable daily intake (TDI) from 4 micrograms to 0.2 nanograms per kilogram of body weight (BW) per day.
In literature, the amount of data on the influence of BPA on human health is consistent. Bisphenol S (BPS) is one of the currently authorised substitute of BPA and is used as a monomer in the manufacture of plastic FCM. BPS is more heat-stable and photo-resistant than BPA, and therefore commonly replaces BPA. The maximum permited amount of BPS exposure is 20 mg/kg BW per day. According to recent literature, BPS is a suspected endocrine disruptor. There are indications that it may have effects on reproduction and furthermore concerns have been raised based on its structural similarity with bisphenol A. 

The third substance considered in the present project is a well-studied industrial chemical, perfluorooctanesulfonic acid (PFOS) and it belongs to PFASs. PFOS has been listed in the Stockholm Convention on Persistent Organic Pollutants (2009), and its production has been halted in many countries. However, PFOS shows environmental persistence and bioaccumulation because the high-energy carbon-fluorine bond can make it resistant to hydrolysis, photolysis, microbial degradation and vertebrate metabolism. PFASs are often classified as EDC, they can potentially interfere with the endocrine system. Some in-vitro studies showed that PFASs can disrupt some hormone functions. Currently, a tolerable weekly intake of 4.4 ng/kg BW per week of the four most found PFAS was established by EFSA. 

There is increasing evidence showing that EDCs can work together to produce additive effects (‘mixture effect’) so that exposure to a combination of EDCs may produce an adverse effect at concentrations at which individually it is not shown (20). There is consensus that the most sensitive window of exposure to EDCs is during important periods of development, such as foetal development or infancy (9,21). Exposure to EDCs during these periods may cause permanent adverse effects later in life (22, 23). 

Aims 

The aim of the present project is to investigate the exposure of BPA, BPS and PFOS at the concentrations suggested by EFSA or lower in order to explore eventual adverse effects compared to EFSA thresholds. The exposure is settled to be during pregnancy and lactation. The behaviour of dams and their offsprings are going to be tested to evidence any possible effect on anxiety and memory, compared between groups and sexes. Growth parameters are going to be monitored daily in order to register any interference with the development, puberty’s onset and weight. Any possible outcome of the mixture effect between the three substances, BPA, BPS, PFOS is evaluated. Lastly, an important goal of the present study is to determine if the sex can be a relevant variable in the outcomes of the chemical exposure and if it could lead to a dimorphic effect.

Research activities

2025

  • September 3rd -5th, 20th Meeting of the Spanish Society for Neuroscience (SENC 2025) - Poster Presentation "Developmental, Reproductive and Metabolic effects of Endocrine Disruptors"
  • July 3th, Reunión Anual de Investigación - Departamento de Anatomía, Histología y Neurociencia UAM, Oral Presentation "Developmental, Reproductive and Metabolic effects of Endocrine Disruptors"
  • June 19th-20th, Cajal Junior 2025 conference, Oral Presentation "Developmental, Reproductive and Metabolic effects of Endocrine Disruptors"
  • May - July 2025, Erasmus+ Traineeship scholarship at Universidad Autonoma de Matrid

 

2024

  • September 12-13, 1st Annual Society for Behavioral Neuroendocrinology Online Research Symposium
  • September 2024 - May 2025, Erasmus+ Study scholarship at Universidad Autonoma de Matrid
  • July 4th-5th, Cajal Junior 2025 conference, Poster Presentation "Study on the role of EDCs in brain development"
  • July 3th, Reunión Anual de Investigación - Departamento de Anatomía, Histología y Neurociencia UAM, Oral Presentation "Study on the role of EDCs in brain development"
  • June 21st, Fast confocal fluorescence imaging and targeted photoactivation in freely behaving mice, Prof. C. Ventalon, 0,5 ECTS
  • June 20, actividad formativa transversal “Investigación Doctoral e Inteligencia Artificial” (2h), Universidad Autonoma de Madrid
  • June 13th and 14th, Workshop "how to write a grant"
  • May 22nd-24th, XII Cajal conference on ”Sex and epigenetics in mental disorders”, Poster Presentation
  • May 10th, Advances in diagnosis and treatment of mood disorders: studies on biomarkers and drug repurposing, G.Rosso, G.Di Salvo, 1,5 ECTS
  • May 7th, Approvment of the cotutelle agreement with Universidad Autonoma de Madrid, under the supervion of professor Daniela Grassi (departamento de Anatomía, Histología y Neurociencia)
  • March 21st, "Corso di formazione SPECIFICA alla Salute e Sicurezza per i Lavoratori (artt. 37-169-227-239-278 del DLgs 81/08)”, e-learning, 4,5 ECTS
  • February 24-27, Congress 12Th International Meeting Steroids And Nervous System, Local organiser & Poster presentation
  • February 21st, Cellular Crosstalk in Neurodevelopmental Disorders, S.Cappello, 0,5 ECTS
  • February 15th, Presentation at First Year PhD Data Report - XXXVIII cycle, 0,5 ECTS
  • February 14th, 23rd, 28th; March 6th, 13th, 20th, From neural cell excitability to brain circuit recording, visualization and manipulation, E.Hoxha, F.Ferrini, V.Carabelli, S.Bovetti, S.Zucca, G.Concina, 4,5 ECTS
  • January 8th-February 1st, Curso “Diseño de experimentos y capacitación para el uso de animales de laboratorio” (80h), Universidad Autonoma de Madrid

 

2023

  • November 17th and 18th, Workshop: Public Engagement And Outreach, A. Buffo, G. Ciocca, D. Ramani, 2,5 ECTS
  • September 28th and October 3rd, Seminar Tools And Indicators In The Procedures For Evaluating And Analysing Scientific Output
  • September 14, SINS National Meeting of Phd Students in Neuroscience; Poster Presentation: "Impact of Early-Life Stress And Gonadal Hormones On The Reward Systems Of ABA Rats"
  • September 14-17, National Congress of the Italian Society for Neuroscience (SINS). Oral Presentation: "Impact of Early-Life Stress And Gonadal Hormones On The Reward Systems Of ABA Rats"
  • June 26-29, Congress 27th Meeting of the Society of Behavioral Neuroendocrinology (SBN), Poster presentation: "Early-Life Stress And Gonadal Hormones: Impact On The Reward Systems Of ABA Rats"
  • June 15th, Corpus Curiosum - Lecture Series V - Is technology a ‘bad influence’ for our brains? Neuroscientific perspectives of smart device usage, Dr L. V. Zamora
  • June 9th, 16th, 23th, 2023, Advanced Course: 'Neuropsychophysiology of the placebo and nocebo phenomena’, M. Amanzio, 2.5 ECTS
  • June 6th, NICO NeuroWebinar: “Electrified brains: from the torpedo fish to transcranial direct current stimulation”, M. Cambiaghi
  • May 30th, Seminar Cycle of the PhD in Neuroscience in Turin: "Choroid plexus: a new entry point to study brain development”, Dott. A. Patrizi, 0,5 ECTS
  • May 19th, NICO NeuroWebinar: “Pharmacologically induced changes in osteocalcin levels – metabolic and central nervous system effects in healthy and metabolic rats”, S. G. Marinova
  • May 12nd, Thesis defence "Investigating the impact of CDKL5 on grey matter myelination through mouse models analysis”, Dott.ssa Sunaina Devi (Tutor. Prof. M. Giustetto), 0,5 ECTS
  • March 13th-14th, Ethics of research and Responsible research, D. Ovadia, 2 ECTS
  • February 23th-24th, symposium "State of the art on Steroids and Nervous System: In memory of Giancarlo” (online)
  • February 16th, Epidemiology TALKS, ALS: translating genetic discoveries into therapies, 0,5 ECTS
  • February 15th, First Year PhD Data Report - XXXVII cycle, attendance, 0,5 ECTS
  • February 10th, 17th, 24th, Introduction to Research Methodology, D. Romano, 3 ECTS
  • January 11th, Clinical, methodological and theoretical aspects of translational and cognitive neuroscience, M. Giustetto, A. Berti, A. Chiò, 2 ECTS

 

2022

  • December 7th, Welcome meeting XXXVIII cycle and 1st Enrica Marzola award ceremony
Last update: 14/09/2025 16:15
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