Effects of xenobiotics from hihgly polluted areas on female reproduction, immune, and nervous systems
Progetto The aim of this multidisciplinary project integrating chemistry, molecular biology
and genetics is to investigate the link between environmental exposures and
human health, with particular regard to modifications occurring to immune and
nervous system, and to female germ cells and embryos.
The basis relies on some preliminary analyses on different persistent organic
pollutants detected in female volunteers from two different areas in the Italian
region of Campania known as “Land of Fires (waste pollution) and the “Sele
Valley” (low pollution). By analyzing biological matrices, such as hair and urine,
of the 2 groups of female donors, we will reconstruct their individual profiles of
exposure to identify the quality and amount of xenobiotics and their metabolites
present in donated samples. The determination of the mixture of xenobiotics (MX)
will be instrumental to assess their acute and chronic effects on immune and
nervous system as well as oocytes and embryos, using omics technologies and
molecular analyses. Indeed, a significant reciprocal interaction occurs between
nervous, reproductive and immune systems able to maintain body homeostasis.
The cell lines used in the experiments are well-controlled systems and
cytotoxicity, growth rate, gene expression change, intracellular metabolites may
be measured by various high-throughput assays with fewer confounding factors
than clinical samples. The SH-SY5Y human neuroblastoma cell line, maintained
as neuroblasts or differentiated into more neuron-like morphologies, and THP-1
immune cells, used to investigate/estimate immune-modulating effects of
compounds in both activated and resting conditions of the cells,will allow us to
focus the neurotoxic and proinflammatory effects of xenobiotic substances.
Concerning female germ cells, the impact of MX on the acquisition of oocyte
developmental competence and regular development of preimplantation embryos
will be assessed by widely used in vitro animal models (mouse) that cover for the
lack of human oocytes/embryos available for these experiments. DNA
methylation and gene expression changes in either human cells, mouse oocytes
and preimplantation embryos upon exposure of xenobiotics will be determined by
bulk and single-cell whole-genome bisulfite sequencing (BS-seq) and RNA seq.
This approach is in line with topics of Italian National Recovery and Resilience
Plan (Piano Nazionale di Ripresa e Resilienza, PNRR) and emerging strategies
related to the objectives of a cluster of the European Research Framework
Program e innovation 2021-2027. The project is focused on the human wellbeing
strategic theme within Cluster Health, subcluster 2, and is based on a
multidisciplinary approach to investigate the relationship between health and the
environment, considering food choices, industrialization, lifestyle and pollution of
environmental resources