Environment and health: endocrine disruptors and biomediation
According to the definition adopted by the European Union “Endocrine Disruptors Chemicals (EDCs) are exogenous substances, or a mixture, that alter function(s) of the endocrine system, causing adverse health effects in an organism, or its progeny, or (sub) population”(European Workshop on the Impact of Endocrine Disrupters on Human Health and Wildlife, Weybridge, UK, 2-4 /12/1996).
The list of these compounds is very broad and includes organochlorine pesticides, polychlorinated biphenyls (PCBs), phthalates, dioxins, furans, antifouling paints, Bisphenol-A and many other anthropogenic organic compounds. Many of them possess chemical-physical characteristics which allow their persistence in the environment for long periods of time and their accumulation in fat and in tissues of animals, including humans, through the food chain.
A common feature of IE is to interfere, through mechanisms of competition or antagonism, with the physiological functions of endocrine structures such as the hypothalamus, pituitary gland, gonads, thyroid, parathyroid, adrenal, pancreas, thus representing an actual risk for human health and environment. This occurs through molecular mechanisms that either prevent the cell to respond properly to the normal endogenous stimuli exercised by the hormone or impact on various fundamental functions, including the nervous and immune systems.
Exposure to environmental pollutants and in particular to EDCs, including heavy metals, is frequently associated to a number of conditions such as an increased incidence of malformations of the male urogenital tract (cryptorchidism, hypospadias) at birth, testicular cancer during adolescence, endometriosis, increased incidence of abortion, premature puberty, obesity, diabetes, breast and prostate cancer and thyroid function abnormalities. In addition, the appearance of clinical or subclinical alterations related to learning, attention and emotional disorders appear to be due to the exposure during the embryogenesis to environmental contaminants such as organochlorines, organophosphates, herbicides, and heavy metals. Embryonic and fetal periods as well as childhood are considered the most sensitive and delicate time as exposure to environmental pollutants in these phases of life can cause diseases and disorders that develop later in life or in subsequent generations.
The increasing presence of EDCs from different sources in the aquatic environment has led in recent decades to deepen the knowledge on environmental levels of these substances and their possible impact on development and reproduction of wild populations. Adverse effects described in aquatic organisms (mammals, birds, reptiles, fish and shellfish), derived from observations in their natural habitats and from laboratory studies (exposure of organisms to specific substances or matrices), include alterations of reproductive and thyroid functions with consequent alteration of neuroendocrine development in the early stages of life, decreased survival of new born and altered reproductive behaviour in adulthood.
In addition, the phenomena of demasculation and feminization, masculinization and defeminization, sex inversion, imposex, which have been linked to exposure to EDCs are further signs of reduced fertility with possible consequential effects for the bioconservation of the species and the preservation of their existing balance in the ecosystem. In Italy, the environment and humans exposure to the EDCs has been and still is the subject of major scientific initiatives such as the dedicated website of the Department of Health Food Safety and Veterinary of the Institute of Health or the establishment of a Working Group for Monitoring the exposure to Endocrine Disrupters organized by the National Committee for Biosafety and Biotechnology which had as its main objective the development of guidelines both for scientific purposes and for promoting measures to increase the quality of life of the population. More recently on the INBB’s website (www.inbb.it) the results of a census on the Italian research teams, academic or private, working on EDCs have been published. From the census it is possible to derive as the Italian research in this field is very active and that no aspect from the clinic to molecular biology, from the environment to toxicology, from epigenetic to food safety is neglected.
In the light of these considerations, in the recent years INBB organized a task force able to study and solve a wide range of issues related to health and environment.
Some results obtained by the INBB researchers in the field include, for example:
- the development of biosensors, classic and innovative, for the identification of EDCs in various matrices: biological fluids, foods, tissues and organ extracts, environmental matrices, etc;
- the study of the molecular mechanisms underlying pathologies induced by IE and in particular endometriosis, obesity, diabetes, cardiovascular disease, and cancer;
- the development of systems for non-invasive detection of biomarkers of estrogenicity and the application of morphological endpoints for the evaluation of the effects of anti-estrogenic and anti-androgenic compounds in aquatic species in their natural environment;
- the assessment of the effect of exposure to obesogenic contaminants on reproduction, detoxification, lipid metabolism and appetite control in aquatic species;
- the identification of biomarkers of exposure through the observation of differences in gene expression in subjects (i.e. fishes, molluscs, amphibians, etc.) grown in polluted and unpolluted environments;
- the development of systems of environmental restoration through bioremediation processes such as immobilized enzymes and / or biofilms and photo-remediation;
- the study of a “gender” response to endocrine disruptors.
The strength of these expertises is easily documented by the numerous national and international collaborations of INBB structure or by the individual research units. Just to give an example these collaborations include: the National Institute of Health, the National Research Council, the Institute for Animal Disease Prevention, ISPRA, Regional Agencies for Environmental Protection and the Environment, IRCS, Regions, IZS, etc.. The commitment of INBB researchers in this specific area is also reported from the activity reports submitted as part of the INBB National Conferences, among whom there were those relating to INBB IX National Conference, held in Rome on 21-22 October 2010 and the X INBB National Conference, held in Rome on 22-23 October 2012, whose detailed programs and abstracts of the reports are on the INBB website.
For the future, research priorities by INBB researchers will remain the development and application of new in vitro and in vivo screening methods, including the application of non-invasive biomarkers of exposure and effect, of novel biosensors and the acquisition an ever deeper knowledge of the mechanisms of action by which the EDCs, alone or in mixture, interact with living systems. The alert on known and emerging EDCs must also be related, in a more precise way, to the risk of exposure through food intake inculcating, even in the common citizen, the awareness of the insidiousness of substances such as EDCs which, although present in small concentrations, are able to induce/increase pathological effects often in several generations.
In addition the INBB National Laboratory on Endocrine Disruptors, located at the Institute of Genetics and Biophysics of the CNR in Naples, is available for different INBB research unities and operates on the Platform “Environment and Health: endocrine disruptors and bioremediation”. Very active are the collaboration with the INBB units operating in the Polytechnic University of Marche in Ancona, in the Universities of Genoa, Messina, Milan, Naples Federico II, Second University of Naples, Parma, Roma Tor Vergata, Roma Tre.
SOME RECENT PUBLICATIONS
- Baker Me, Vidal-Dorsch De, Ribecco C, Sprague Lj, Angert M, Lekmine N, Ludka C, Martella A, Ricciardelli E, Bay Sm, Gully Jr, Kelley Km, Schlenk D, Carnevali O, Sášik R, Hardiman G. (2013) Molecular analysis of endocrine disruption in hornyhead turbot at wastewater outfalls in southern California using a second generation multi-species microarray. PLoS One. 25;8(9):e75553.
- Casati L., Sendra R., Poletti A., Negri-Cesi P., Celotti F. (2013). Androgen receptor activation by polychlorinated biphenyls: epigenetic effects mediated by the histone demethylase Jarid1b. Epigenetics 8:10, 1–8 (ISSN 1559-2294)
- Casati L., Sendra R., Colciago A., Negri Cesi P., Esteller M., Celotti F. (2012). Polychlorinated biphenyls affect histone modification pattern in early development of rats: a role for androgen receptor-dependent modulation? Epigenomics 4(1), 101–112 (ISSN 1750-1911)
- Grasselli E, Cortese K, Voci A, Vergani L, Fabbri R, Barmo C, Gallo G, Canesi L. (2013). Direct effects of Bisphenol A on lipid homeostasis in rat hepatoma cells, Chemosphere, 91,1123-9 *
- La Rosa P, Pellegrini M, Totta P, Acconcia F, Marino M. (2014). Xenoestrogens alter estrogen receptor (ER) α intracellular levels. PLoS One. 20;9(2):e88961.
- Maradonna F., Evangelisti M., Gioacchini G., Migliarini B., Olivotto I., Carnevali O. Assay of vtg, ERs and PPARs as endpoint for the rapid in vitro screening of the harmful effect of Di-(2-ethylhexyl)-phthalate (DEHP) and phthalic acid (PA) in zebrafish primary hepatocyte cultures. Toxicology in Vitro 27 (2013) 84–91
- Menale C., Nicolucci C., Catapane M., Rossi S., Bencivenga U., Mita D.G., Diano N. (2012). Optimization of operational conditions for biodegradation of chlorophenols by laccase-polyacrilonitrile beads system. J Mol Catal. B, Enzym 78, 38– 44
- Mita L, Baldi A, Diano N, Viggiano E, Portaccio M, Nicolucci C, Grumiro L, Menale C, Mita DG, Spugnini EP, Viceconte R, Citro G, Pierantoni R, Sica V, Marino M, Signorile PG, Bianco M. (2012). Differential accumulation of BPA in some tissues of offspring of Balb-C mice exposed to different BPA doses. Environ Toxicol Pharmacol. 33(1),9-15.
- Paiano V., Generoso C., Mandich A., Traversi I., Palmiotto M., Bagnati R., Colombo A., Davoli E., Fanelli R., Fattore E.(2013). Persistent organic pollutants in sea bass (Dicentrarchus labrax L.) in two fish farms in the Mediterranean Sea. Chemosphere, 93, 338-343. *
- Pellegrini M, Bulzomi P, Lecis M, Leone S, Campesi I, Franconi F, Marino M. (2013) Endocrine Disruptors differently influence estrogen receptor β and androgen receptor in male and female rat VSMC. J Cell Physiol. 2013 *