Endocrine disruptor

Coordinator
Patrizia Bovolin

Members
Claudio Dati
Erika Cottone
Davide Lovisolo
Valentina Pomatto

This research investigates the impact of environmental endocrine disrupting chemicals on cell function and viability in vertebrates, with special interests on developmental effects on neural cells involved in the neuroendocrine regulation of reproduction and energy.

 

Central effects of endocrine disruptors

 

Endocrine-disrupting chemicals (EDCs)  may interfere with the body endocrine system and produce adverse effects in both humans and wildlife. A wide range of environmental substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT and other pesticides, and plasticizers such as bisphenol A.  Among environmental EDCs, those employed as plasticizers in the manufacturing of food wrapping materials are very relevant to human health.



The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically in the hypothalamus, and are conveyed first by neural and then by endocrine effectors. Several studies show that EDCs may pose the greatest risk during prenatal and early postnatal development when organs and neural systems are forming.  Adverse consequences may not be apparent until much later in life. In addition, EDCs may affect not just the offspring of mothers exposed to endocrine disruptors during pregnancy, but future offspring as well, by causing alterations in gene expression in germ line cells (eggs and sperm). In other words, epigenetic mechanisms are involved in mediating effects of endocrine disruptors.

 

 

 

 

 

 

 

 

 

 

Our group tries to determine the impact of specific EDCs, especially common plasticizers, on cell function and viability using both in vitro and in vivo approaches:

 EDCs & neurogenesis - We test the impact of selected EDCs on cultured neural progenitor cells, in order to characterize potential effects of these chemicals on cell proliferation, migration, survival, and differentiation. We also try to understand EDC mechanisms at the cellular level by testing intracellular signaling and gene expression.

Obesogenic EDCs - We test potentially obesogenic chemicals (following in silico pre-screening) by quantifying their capability to increase lipid deposition in cultured adipocyte precursor cells.

Neuroendocrine effects of EDCs – We investigate the impact of selected EDCs on different hypothalamic cell lines, representing neurons involved in the central control of reproduction (i.e. GnRH neurons), energy balance and feeding behavior, in order to define active concentrations, cellular functions, molecular targets and intracellular pathways affected by EDCs.

 

 

 

 

 

In collaboration with the “Università Politecnica delle Marche, Ancona” we investigate in vivo both direct effects and transgenerational effects of EDCs on the brain of adult and developing zebrafish.

 

 

 

 

 

 

 

 

The endocannabinoid system is a well-known regulator of vertebrate reproduction, food intake and energy balance. We have demonstrated that the brain endocannabinoid system is sensitive to acute administration of nonylphenol (4NP, a widespread xenoestrogen) in goldfish. Therefore some EDCs might interfere with the endocannabinoid modulatory action in hypothalamus. We search possible interactions between EDCs and the endocannabinoid system both in vivo (goldfish and zebrafish hypothalamus) and in in vitro (hypothalamic cell lines).