Exposure to Endocrine Disrupters and Nuclear Receptor Gene Expression in Infertile and Fertile Women from Different Italian Areas

Abstract

Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERα, ERβ, AR, AhR, PPARγ, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARγ. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health.

Evidence for bisphenol A-induced female infertility: a review (2007–2016)

“…Epidemiological studies examined if BPA levels are higher in infertile women than in fertile women (Table 1). Findings from these studies indicate that infertile women have higher serum BPA levels compared to fertile women (17, 18). Further, studies conducted in women undergoing in vitro fertilization (IVF) treatments show that BPA levels (total or unconjugated BPA) were inversely associated with peak estradiol levels, number of oocytes retrieved, oocyte maturation, fertilization rates, and embryo quality (19–23).…”

Transcriptional profiling and biological pathway analysis of human equivalence PCB exposure in vitro: Indicator of disease and disorder development in humans

“…metabolic disorders (including obesity and diabetes) cardiovascular, endocrine disruption, and cancers, in accord with results observed in epidemiological settings (Langer et al, 2014; Arrebola et al, 2014; Recio-Vega et al, 2013; Lee et al, 2014; Wadzinski et al, 2014; Pereira-Fernandes et al, 2014; Sexton et al, 2013, Casas et al, 2014). Research utilizing PBMC cells in human are now being widely used to test for the efficacy of new drugs and treatments, to divulge the differential gene expression patterns induced by toxicity, and to study downstream effectors, all of which can be used as a potential source for developing disease-specific biomarkers (Reynes et al, 2014; Saidijam et al, 2014; Roccaet et al, 2014; Kong 2014). In such a model, studying the gene expression changes might provide us a valuable insights and better understanding of their mechanism(s) of action by highlighting which enzymes or proteins are targeted by these exposures.…”

Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women

“…Exposure to PM may disturb normal physiological pathways that maintain homeostasis and this may activate cellular processes that mediate the adverse effects of PM (Kleensang et al 2014). Gene expression changes play an important role in the activation of pathways of toxicity and gene signatures have the potential to serve as biomarkers of exposure (van Leeuwen et al 2008; van Breda et al 2015) and recent reports demonstrate their potential use as biomarkers of effect (La Rocca et al 2014; Fink et al 2014). As it has been shown previously that transcriptomic responses to diverse environmental stimuli (i.e., chemical exposure, smoking) can be significantly different between men and women (De Coster et al 2013; Paul and Amundson 2014), we have opted to perform a sex-specific analysis.…”