A comprehensive evaluation of organic contamination was performed in sediments sampled in two reference and three impacted small streams where endocrine disruptive (ED) effects in fish have been evidenced. The approach combined quantitative chemical analyses of more than 50 ED chemicals (EDCs) and a battery of in vitro bioassays allowing the quantification of receptor-mediated activities, namely estrogen (ER), androgen (AR), dioxin (AhR) and pregnane X (PXR) receptors. At the most impacted sites, chemical analyses showed the presence of natural estrogens, organochlorine pesticides, parabens, polycyclic aromatic hydrocarbons (16 PAHs), bisphenol A and alkylphenols, while synthetic steroids, myco-estrogens and phyto-estrogens were not detected. Determination of toxic-equivalent amounts showed that 28–96% of estrogenic activities in bioassays (0.2–6.3 ng/g 17β-estradiol equivalents) were explained by 17β-estradiol and estrone. PAHs were major contributors (20–60%) to the total dioxin-like activities. Interestingly, high PXR and (anti)AR activities were detected; however, the targeted analysed compounds could not explain the measured biological activities. This study highlighted the presence of multiple organic EDCs in French river sediments subjected to mixed diffuse pollution, and argues for the need to further identify AR and PXR active compounds in the aquatic environment. Multiple endocrine disrupting chemicals (ER, AR, AhR and PXR ligands) are detected in French river sediments using a panel of in vitro bioassays and analytical methods.

Bisphenol A (BPA) is an endocrine disrupting chemical able to promote hormone-responsive tumors. The major route of BPA contamination being oral, the aim of the present study was to investigate BPA effects on oral cells. Here, we evaluated the impact of sub-chronic in vivo exposure to BPA and its in vitro effects on neoplastic and non-neoplastic oral cells. We evaluated the oral mucosa of mice chronically exposed to BPA (200 mg/L). The response of keratinocytes (NOK–SI) and Head and Neck (HN) Squamous Cell Carcinoma (SCC), HN12 and HN13 cell lines to BPA was examined. In vivo, BPA accumulated in oral tissues and caused an increase in epithelial proliferative activity. BPA disrupted the function of keratinocytes by altering pro-survival and proliferative pathways and the secretion of cytokines and growth factors. In tumor cells, BPA induced proliferative, invasive, pro-angiogenic, and epigenetic paths. Our data highlight the harmful effects of BPA on oral mucosa and, tumorigenic and non-tumorigenic cells. Additionally, BPA may be a modifier of oral cancer cell behavior by prompting a functional shift to a more aggressive phenotype.

Estrogenic endocrine disrupting chemicals (EDCs) are natural hormones, synthetic compounds or industrial chemicals that mimic estrogens due to their structural similarity with estrogen's functional moieties. They typically enter aquatic environments through wastewater treatment plant effluents or runoff from intensive livestock operations. Globally, most natural and synthetic estrogens in receiving aquatic environments are in the low ng/L range, while industrial chemicals (such as bisphenol A, nonylphenol and octylphenol) are present in the μg to low mg/L range. These environmental concentrations often exceed laboratory-based predicted no effect concentrations (PNECs) and have been evidenced to cause negative reproductive impacts on resident aquatic biota. In vertebrates, such as fish, a well-established indicator of estrogen-mediated endocrine disruption is overexpression of the egg yolk protein precursor vitellogenin (Vtg) in males. Although the vertebrate Vtg has high sensitivity and specificity to estrogens, and the molecular basis of its estrogen inducibility has been well studied, there is growing ethical concern over the use of vertebrate animals for contaminant monitoring. The potential utility of the invertebrate Vtg as a biomonitor for environmental estrogens has therefore gained increasing attention. Here we review evidence providing support that the molluscan Vtg holds promise as an invertebrate biomarker for exposure to estrogens. Unlike vertebrates, estrogen signalling in invertebrates remains largely unclarified and the classical genomic pathway only partially explains estrogen-mediated activation of Vtg. In light of this, in the latter part of this review, we summarise recent progress towards understanding the molecular mechanisms underlying the activation of the molluscan Vtg gene by estrogens and present a hypothetical model of the interplay between genomic and non-genomic pathways in the transcriptional regulation of the gene.

Bisphenol A (BPA) has been considered as an endocrine disruptor due to its ability to interact with estrogen receptors (ERs). While G protein-coupled receptor 30 (GPR30) is a novel estrogen receptor, its role in BPA-induced activation of Erk1/2 remains unknown. Human breast cancer cell lines, MCF-7, MDA-MB-231 and SKBR3, were used as experimental models to discriminate between ERs-dependent, putative ERs-independent and/or GPR30-associated effects. BPA induced a rapid activation of Erk1/2 in both ERα/β-positive and negative breast cancer cells, and this effect was not blocked with an ER antagonist, ICI 182,780. A small interfering RNA assay revealed that the expression of GPR30 was necessary for BPA-induced activation of Erk1/2 and transcriptional regulation of c-fos. In addition, BPA regulates the expression of c-fos likely through an AP1-mediated pathway. As a conclusion, GPR30 plays an important role in the BPA-induced activation of Erk1/2 in a manner distinguishable from that in ERα-mediated signaling.

The transcriptomes of Zhikong scallop exposed to 17β-estradiol were determined using the Roche/454. A total of 51,997 unigenes, representing 45,030 contigs and 6967 singlets were obtained. And 14,028, 19,798 and 14,981 of these unigenes were annotated from the non-redundant nucleic acid database, non-redundant protein database and Swiss protein database, respectively. A total of 10,699 unigenes were further annotated to biological processes (9080), molecular functions (8692) and cellular components (7829) using the GO, and 8945 unigenes were mapped to biological pathways including the metabolism (2862) and genetic information processing (2263). Most importantly, 16,692 unigenes and 18,686 unigenes in testis, and 10,492 unigenes and 13,186 unigenes in digestive gland were up-regulated significantly after exposure to 50 and 500ngE2/L; while 10,212 unigenes and 9409 unigenes in testis and 10,629 unigenes and 9463 unigenes in digestive gland were down-regulated. These valuable information provides insights into the mechanisms in invertebrate exposure to EDCs.

Chemicals in air were characterized for potential interference with signaling of estrogen, androgen, and arylhydrocarbon (AhR) receptors, which are known to play an important role in endocrine-disruptive changes in vivo. Previously, effects of this type have been studied mainly in particulate matter in the ambient air from various localities. In this study, both volatile and particulate fractions of air from three sites in Banja Luka region (Bosnia and Herzegovina) were investigated to describe the distribution of endocrine-disrupting contaminants on a small spatial scale. Circadian variability of air pollution was investigated by collecting samples during both day and night. Air samples collected from urban localities at night were more potent in producing the AhR-mediated effects than those collected during daytime. This trend was not observed at the reference rural location. None of the samples showed significant estrogenic or androgenic activity. On the other hand, anti-androgenicity was detected in both particulate and vapor phases, while anti-estrogenicity was detected only in the particulate fraction of air from all localities. The AhR-mediated potencies of samples were associated primarily with non-persistent compounds. Based on the concentrations of 28 individual compounds, PAHs accounted for approximately 30 % of the AhR-mediated potency determined by the bioassay. The results show that there can be a significant difference between levels of bioactive compounds in air between daytime and nighttime.

Perfluorinated compounds (PFCs) are a large group of chemicals used in different industrial and commercial applications. Studies have suggested the potential of some PFCs to disrupt endocrine homeostasis, increasing the risk of adverse health effects. This study aimed to elucidate mechanisms behind PFC interference with steroid hormone receptor functions. Seven PFCs [perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA)] were analyzed in vitro for their potential to affect estrogen receptor (ER) and androgen receptor (AR) transactivity as well as aromatase enzyme activity. The PFCs were assessed as single compounds and in an equimolar mixture. PFHxS, PFOS and PFOA significantly induced the ER transactivity, whereas PFHxS, PFOS, PFOA, PFNA and PFDA significantly antagonized the AR activity in a concentration-dependent manner. Moreover, PFDA weakly decreased the aromatase activity at a high test concentration. A mixture effect more than additive was observed on AR function. We conclude that five of the seven PFCs possess the potential in vitro to interfere with the function of the ER and/or the AR. The observed mixture effect emphasizes the importance of considering the combined action of PFCs in future studies to assess related health risks.