This study examines the impact of estrogenic compounds like bisphenol A (BPA), estradiol (E2), and zearalenone (ZEA) on human ovarian cancer, focusing on constructing a risk model, conducting Gene Set Variation Analysis (GSVA), and evaluating immune infiltration. Differential gene expression analysis identified 980 shared differentially expressed genes (DEGs) in human ovarian cells exposed to BPA, E2, and ZEA, indicating disruptions in ribosome biogenesis and RNA processing. Using the Cancer Genome Atlas Ovarian Cancer (TCGA-OV) dataset, a least absolute shrinkage and selection operator (LASSO)-based risk model was developed incorporating prognostic genes 4-Hydroxyphenylpyruvate Dioxygenase Like (HPDL), Thy-1 Cell Surface Antigen (THY1), and Peptidase Inhibitor 3 (PI3). This model effectively stratified ovarian cancer patients into high-risk and low-risk categories, showing significant differences in overall survival, disease-specific survival, and progression-free survival. GSVA analysis linked HPDL expression to pathways related to the cell cycle, DNA damage, and repair, while THY1 and PI3 were associated with apoptosis, hypoxia, and proliferation pathways. Immune infiltration analysis revealed distinct immune cell profiles for high and low expression groups of HPDL, THY1, and PI3, indicating their influence on the tumor microenvironment. The findings demonstrate that estrogenic compounds significantly alter gene expression and oncogenic pathways in ovarian cancer. The risk model integrating HPDL, THY1, and PI3 offers a strong prognostic tool, with GSVA and immune infiltration analyses providing insights into the interplay between these genes and the tumor microenvironment, suggesting potential targets for personalized therapies.

In aquatic ecosystems, endocrine-disrupting compounds (EDCs) pose a growing concern for their potential adverse effects on fish reproduction and development. In lake Pyhäjärvi, located in the urban boreal region of Tampere, Finland, a significant number of sexually immature pikeperch (Sander lucioperca) individuals have been identified in size and age categories that are expected to be sexually mature. To explore if this phenomenon is attributed to estrogenic endocrine disruption, we conducted a comprehensive study comparing fish from lake Pyhäjärvi with those from a nearby reference lake, lake Näsijärvi. Roach (Rutilus rutilus), known for its susceptibility to EDCs, was also included for comparison. We examined various parameters in both pikeperch and roach, including size, condition factor, age, reproductive indicators, biometric indices and gonadal histology. We also assessed liver vitellogenin mRNA levels and genetic sex in roach, and measured estrogen levels in lake waters and wastewater treatment plant effluents. Results revealed that approximately one-third of fish in both species exhibited sexual immaturity in lake Pyhäjärvi, with a female-biased sex ratio. Surprisingly, we found no signs of estrogenic endocrine disruption, indicated by the absence of intersex fish in both species. Furthermore, vitellogenin levels in roach closely resembled those in the reference lake. Estrogens were undetectable in the lake waters, suggesting that factors other than estrogenic EDCs, including other potential endocrine disruptors such as PCBs or heavy metals, may be influencing delayed sexual maturity and skewed sex ratios. Further inquiry is needed to pinpoint these underlying causes. Our study provides essential baseline information on fish sexual development in lake Pyhäjärvi, emphasizing the need for ongoing monitoring and research to understand delayed sexual maturity and biased sex ratios. This is vital given the increasing concern about EDC impacts on aquatic ecosystems and the necessity for effective management strategies to protect these ecosystems\' health and integrity.

Pharmaceuticals, personal care products (PPCPs), and endocrine-disrupting compounds (EDCs) have seen a recent sustained increase in usage, leading to increasing discharge and accumulation in wastewater. Conventional water treatment and disinfection processes are somewhat limited in effectively addressing this micropollutant issue. Ultrasonication (US), which serves as an advanced oxidation process, is based on the principle of ultrasound irradiation, exposing water to high-frequency waves, inducing thermal decomposition of H2O while using the produced radicals to oxidize and break down dissolved contaminants. This review evaluates research over the past five years on US-based technologies for the effective degradation of EDCs and PPCPs in water and assesses various factors that can influence the removal rate: solution pH, temperature of water, presence of background common ions, natural organic matter, species that serve as promoters and scavengers, and variations in US conditions (e.g., frequency, power density, and reaction type). This review also discusses various types of carbon/non-carbon catalysts, O3 and ultraviolet processes that can further enhance the degradation efficiency of EDCs and PPCPs in combination with US processes. Furthermore, numerous types of EDCs and PPCPs and recent research trends for these organic contaminants are considered.

The occurrence of pharmaceuticals and xenoestrogen compounds (PXCs) in drinking water presents a dire human health risk challenge. The problem stems from the high anthropogenic pollution load on source water and the inefficiencies of the conventional water treatment plants in treating PXCs. This study assessed the PXCs levels and the consequential health risks of exposure to tap water from selected Ghanaian communities as well as that of raw water samples from the respective treatment plants. Thus the PXCs treatment efficiency of two drinking water treatment plants in the metropolises studied was also assessed. The study also conducted source apportionment of the PXCs in the tap water. Twenty six (26) tap and raw water samples from communities in the Cape Coast and Sekondi-Takoradi metropolises were extracted using SPE cartridges and analysed for PXCs using Ultra-fast-HPLC-UV instrument. Elevated levels of PXCs up to 24.79 and 22.02 μg/L were respectively recorded in raw and tap water samples from the metropolises. Consequently, elevated non-cancer health risk (HI > 1) to residential adults were found for tap water samples from Cape Coast metropolis and also for some samples from Sekondi-Takoradi metropolis. Again, elevated cumulative oral cancer risks >10-5 and dermal cancer risk up to 4 × 10-5 were recorded. The source apportionment revealed three significant sources of PXCs in tap water samples studied. The results revealed the inefficiency of the treatment plants in removing PXCs from the raw water during treatments. The situation thus requires urgent attention to ameliorate it, safeguarding public health. It is recommended that the conventional water treatment process employed be augmented with advanced treatment technologies to improve their efficacy in PXCs treatment.

Alaska contains over 600 formerly used defense (FUD) sites, many of which serve as point sources of pollution. These sites are often co-located with rural communities that depend upon traditional subsistence foods, especially lipid-rich animals that bioaccumulate and biomagnify persistent organic pollutants (POPs). Many POPs are carcinogenic and endocrine-disrupting compounds that are associated with adverse health outcomes. Therefore, elevated exposure to POPs from point sources of pollution may contribute to disproportionate incidence of disease in arctic communities. We investigated PCB concentrations and the health implications of POP exposure in sentinel fishes collected near the Northeast Cape FUD site on Sivuqaq (St. Lawrence Island), Alaska. Sivuqaq residents are almost exclusively Yupik and rely on subsistence foods. At the request of the Sivuqaq community, we examined differential gene expression and developmental pathologies associated with exposure to POPs originating at the Northeast Cape FUD site. We found significantly higher levels of PCBs in Alaska blackfish (Dallia pectoralis) collected from contaminated sites downstream of the FUD site compared to fish collected from upstream reference sites. We compared transcriptomic profiles and histopathologies of these same blackfish. Blackfish from contaminated sites overexpressed genes involved in ribosomal and FoxO signaling pathways compared to blackfish from reference sites. Contaminated blackfish also had significantly fewer thyroid follicles and smaller pigmented macrophage aggregates. Conversely, we found that ninespine stickleback (Pungitius pungitius) from contaminated sites exhibited thyroid follicle hyperplasia. Despite our previous research reporting transcriptomic and endocrine differences in stickleback from contaminated vs. reference sites, we did not find significant differences in kidney or gonadal histomorphologies. Our results demonstrate that contaminants from the Northeast Cape FUD site are associated with altered gene expression and thyroid development in native fishes. These results are consistent with our prior work demonstrating disruption of the thyroid hormone axis in Sivuqaq residents.

There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3-8.5 years). In females, PFAS inhibit the hypothalamic-pituitary-gonadal (HPG) axis, reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to the inhibition of androgen and estradiol production. PFAS have been found to cause detrimental effects on egg quality through impairing folliculogenesis. In males, PFAS can impair sperm motility and morphology: two fundamental qualities of successful fertilization. PFAS exposure has been proven to inhibit testosterone production, sperm capacitation, and acrosomal reaction. After fertilization, the results of PFAS exposure to embryos have also been investigated, showing reduced development to the blastocyst stage. The aim of this review is to report the main findings in the literature on the impact of PFAS exposure to gamete competency and fertilization capability by highlighting key studies on both male and female fertility. We report that there is significant evidence demonstrating the negative impacts on fertility after PFAS exposure. At high doses, these environmentally abundant and widespread compounds can significantly affect human fertility.

Exposure to endocrine-disrupting chemicals (EDCs) in freshwater systems has garnered increasing attention. A comprehensive analysis of the migration patterns, bioaccumulation, and consumer health risk of EDCs along the Xiangjiang River due to fish consumption from the river ecosystem was provided. Twenty natural and synthetic target EDCs were detected and analyzed from the water, sediments, and fish samples collected along the Xiangjiang River. There were significant correlations between the EDC concentrations in fish and the sediments. This revealed that EDCs in sediments play a dominant role in the uptake of EDCs by fish. The bioaccumulation factor and biota-sediment accumulation factor were calculated, with the highest values observed for nonylphenol. Pearson\'s correlation analysis showed that bisphenol A is the most reliable biological indicator of EDC contamination in fish. Furthermore, based on the threshold of toxicological concerns and the health risk with dietary intake, crucian carp and catfish from the Xiangjiang River pose a certain risk for children and pregnant women compared to grass carp. The Monte Carlo simulation results indicated a certain risk of cumulative ∑EDC exposure for local residents due to fish consumption.

High-performance thin-layer chromatography hyphenated with planar multiplex bioassays and high-resolution tandem mass spectrometry contributes to the non-target detection or even identification of active compounds in complex mixtures such as food, feed, cosmetics, commodities, and environmental samples. It can be used to discover previously unknown harmful or active substances in complex samples and to tentatively assign molecular formulas. This method is already faster than the commonly used in vitro assays along with liquid chromatographic separations, but overnight cell cultivation still prevents a planar bioassay from being performed within one day. There is also still potential for optimization in terms of sustainability. To achieve this, the planar bioassay protocols for the detection of androgen-like and estrogen-like compounds were harmonized. The successful minimization of the cell culture volume enabled accelerated cell cultivation, which allowed the bioassay to be performed within one day. This was considered a milestone achieved, as up to 23 samples per plate can now be analyzed from the start of cultivation to the biological endpoint on the same day. Doubling the substrate amount and increasing the pH of the silica gel layer led to a more sensitive and selective bioassay due to the enhanced fluorescence of the formed end-product. The faster and more sustainable bioassay protocol was applied to complex samples such as sunscreen and red wine to detect estrogen-like compounds. The developed method was validated by comparison with a standard method.

Environmental conditions experienced within and across generations can impact individual phenotypes via so-called \'epigenetic\' processes. Here we suggest that endocrine signalling acts as a \'sensor\' linking environmental inputs to epigenetic modifications. We focus on thyroid hormone signalling and DNA methylation, but other mechanisms are likely to act in a similar manner. DNA methylation is one of the most important epigenetic mechanisms, which alters gene expression patterns by methylating cytosine bases via DNA methyltransferase enzymes. Thyroid hormone is mechanistically linked to DNA methylation, at least partly by regulating the activity of DNA methyltransferase 3a, which is the principal enzyme that mediates epigenetic responses to environmental change. Thyroid signalling is sensitive to natural and anthropogenic environmental impacts (e.g. light, temperature, endocrine-disrupting pollution), and here we propose that thyroid hormone acts as an environmental sensor to mediate epigenetic modifications. The nexus between thyroid hormone signalling and DNA methylation can integrate multiple environmental signals to modify phenotypes, and coordinate phenotypic plasticity at different time scales, such as within and across generations. These dynamics can have wide-ranging effects on health and fitness of animals, because they influence the time course of phenotypic adjustments and potentially the range of environmental stimuli that can elicit epigenetic responses. This article is part of the theme issue \'Endocrine responses to environmental variation: conceptual approaches and recent developments\'.

The presence of endocrine-disrupting compounds (EDCs) in water poses a significant threat to human and animal health, as recognized by regulatory agencies throughout the world. The Yeast Estrogen Screen (YES) assay is an excellent method to evaluate the presence of these compounds in water due to its simplicity and capacity to assess the bioaccessible forms/fractions of these compounds. In the presence of a compound with estrogenic activity, Saccharomyces cerevisiae cells, containing a lacZ reporter gene encoding the enzyme β-galactosidase, are induced, the enzyme is synthesised, and released to the extracellular medium. In this work, a YES-based approach encompassing the use of a lacZ reporter gene modified strain of S. cerevisiae, microcarriers as solid support, and a fluorescent substrate, fluorescein di-β-d-galactopyranoside, is proposed, allowing for the assessment of EDCs\' presence after only 2 h of incubation. The proposed method provided an EC50 of 0.17 ± 0.03 nM and an LLOQ of 0.03 nM, expressed as 17β-estradiol. The assessment of different EDCs provided EC50 values between 0.16 and 1.2 × 103 nM. After application to wastewaters, similar results were obtained for EDCs screening, much faster, compared to the conventional 45 h spectrophotometric procedure using a commercial kit, showing potential for onsite high-throughput screening of environmental contamination.