Endocrine Disruptors Research Articles

Thematic Review of Endocrine Disruptors and Their Role in Shaping Pubertal Timing

This review examines the inconsistent effects of endocrine-disrupting chemicals (EDCs) and pollutants on pubertal timing, emphasizing the methodological challenges contributing to variability in findings. Data from nine key studies reveal that chemicals such as BPA, phthalates, and PFAS impact pubertal onset differently based on exposure timing, dosage, and sex. For instance, BPA is linked to earlier puberty in girls but delayed onset in boys, while other EDCs show mixed effects across populations. These discrepancies often arise from challenges in study design, such as the difficulty in establishing reliable control groups, accurately measuring exposures, and accounting for confounding factors like socioeconomic status, diet, and obesity. Sex-specific differences and environmental shifts during the COVID-19 pandemic, including increased indoor exposure and stress, further complicate the picture. These factors highlight the urgent need for more robust research methodologies, including standardized exposure assessments and longitudinal studies, to clarify the mechanisms driving these effects. Despite these challenges, the findings stress the importance of public health interventions, such as stricter EDC regulations, improved pollutant monitoring, and minimizing exposures during sensitive developmental windows. Addressing methodological gaps is crucial for producing reliable, actionable insights to protect adolescent development from the adverse effects of EDCs.

Age-Dependent Effects of Butyl Benzyl Phthalate Exposure on Lipid Metabolism and Hepatic Fibrosis in Mice

Endocrine-disrupting chemicals (EDCs), including phthalates, have been implicated in the development of non-alcoholic fatty liver disease (NAFLD) and hepatic fibrosis. This study investigates the age-dependent effects of butyl benzyl phthalate (BBP) exposure on lipid metabolism in the livers of young and aged mice. Young (2-month-old) and aged (20-month-old) male C57BL/6 mice were exposed to BBP through drinking water at a dose of 169 μg/kg/day for 6 and 4 months, respectively. Young mice exposed to BBP showed fatty liver, with downregulation of key fatty acid oxidation genes (CPT1A, CPT1B, CPT2, and Acox1) and elevated pro-inflammatory cytokines (TNF-α and IL-6). In contrast, aged mice exhibited hepatic fibrosis, with increased collagen deposition and upregulation of genes related to fibrosis (Acta2, MMP2, TGF-ß1, and Col1a2), cirrhosis (CXCR4, SOX9, DCN, and MFAP4), and cancer (Bcl2, CDKN2a, c-Myc, and Fn1). Overall, these findings emphasize the importance of age when evaluating the risks of EDC exposure, such as BBP. Future research should focus on understanding the molecular mechanisms behind these age-related differences and explore Grem1 and SOCS3 as potential therapeutic targets for treating EDC-induced and age-related liver diseases.

Efficient photocatalytic degradation of bisphenol A on 2D-3D spherically hierarchical structure Zn5In2S8

Bisphenol A (BPA) poses a significant environmental threat due to its widespread use as an industrial chemical and its classification as an environmental endocrine disruptor. The urgent need for effective BPA removal has driven research toward innovative solutions. In this study, we present the synthesis and application of a novel 2D-3D spherically hierarchical Zn5In2S8 (ZIS) photocatalyst for the photocatalytic degradation of BPA under visible light for the first time. Compared to the conventional g-C3N4 photocatalyst, ZIS exhibits enhanced optical and electrical properties, leading to remarkable photocatalytic performance, with an apparent reaction rate constant of 2.36 h⁻1, 6.56 times greater than that of g-C3N4. This efficacy allows for the degradation of 99.9% of BPA in just 2 h. The photocatalytic mechanism of ZIS was elucidated through various material characterizations and photoelectrochemical assessments, demonstrating improved light absorption and efficient charge separation as key factors facilitating BPA degradation. Notably, ZIS maintains high photocatalytic activity and stability over multiple cycles, indicating its potential as a sustainable photocatalyst. These findings not only contribute to the development of efficient photocatalysts for environmental remediation but also underscore the significant role of Zn5In2S8 in photocatalysis and solar energy conversion.

Associations Between Daily-Use Products and Urinary Biomarkers of Endocrine-Disrupting Chemicals in Adults of Reproductive Age

Background: Daily-use products, including personal care products, household products, and dietary supplements, often contain ingredients that raise concerns regarding harmful chemical exposure. Endocrine-disrupting chemicals (EDCs) found in daily-use products are associated with numerous adverse health effects. Methods: This pilot study explores the relationship between concentrations of EDCs in urine samples and products used 24 h prior to sample collection, and ingredients of concern in those products, in 140 adults of reproductive age in Northern Nevada. Results: Having higher numbers of products and ingredients of concern, especially in the personal care category, was associated with higher levels of mono-(-ethyl-5-carboxypentyl) phthalate (MECPP). Similarly, taking more supplements was associated with higher levels of methylparaben (MePB). In contrast, using household products with more ingredients of concern was associated with lower levels of monobutyl phthalate (MBP). Generally, women used more products, were exposed to more ingredients of concern and had higher urinary metabolites than men. Participants who rated themselves as being in poor/fair health were exposed to more personal care and supplement ingredients of concern than those in better health. Interestingly, those in excellent health also took supplements with more ingredients of concern. Conclusions: Greater product use and more ingredients of concern are associated with urinary metabolites of known EDCs and self-ratings of poor health. Women and people who take supplements are at greater risk, and even people who consider themselves to be healthy can be highly exposed. More education among the general public is needed to make people aware of the presence of these chemicals in their everyday products so they can make efforts to avoid them.

Lower Semen Quality Among Men in the Modern Era—Is There a Role for Diet and the Microbiome?

The prevalence of infertility is increasing worldwide; poor nutrition, increased sedentary lifestyles, obesity, stress, endocrine-disrupting chemicals, and advanced age of childbearing may contribute to the disruption of ovulation and influence oocyte and sperm quality and overall reproductive health. Historically, infertility has been primarily attributed to female factors, neglecting the importance of male fertility; this has resulted in an incomplete understanding of reproductive health. Male factors account for 40–50% of infertility cases. In half of these cases, the proximal cause for male infertility is unknown. Sperm contributes half of the nuclear DNA to the embryo, and its quality is known to impact fertilisation rates, embryo quality, pregnancy rates, risk of spontaneous miscarriage, de novo autosomal-dominant conditions, psychiatric and neurodevelopment conditions, and childhood diseases. Recent studies have suggested that both the microenvironment of the testes and diet quality may play an important role in fertility; however, there is limited research on the combination of these factors. This review summarises current known causes of male infertility and then focuses on the potential roles for diet and the seminal microbiome. Future research in this area will inform dietary interventions and health advice for men with poor semen quality, potentially alleviating the need for costly and invasive assisted reproduction treatments and allowing men to take an active role in the fertility conversation which has historically focussed on women individually.

Skin-Care Obsessed Kids: The Hidden Risks and Healthy Alternatives Every Parent Should Know

The emergence of skincare trends among Generation Alpha has introduced children to beauty regimens at an unprecedentedly young age, largely influenced by social media and adult-targeted marketing. While fostering self-care awareness, this phenomenon raises critical concerns about the safety and appropriateness of such practices for developing skin and overall health. This study investigates the potential health implications of using adult-oriented skincare and cosmetic products, focusing on risks such as hormonal disruptions, allergic reactions, and long-term exposure to harmful ingredients like parabens, phthalates, and formaldehyde. Additionally, the increasing popularity of nail art among children is examined, with attention to the dangers of UV exposure and chemical toxicity. The article advocates for child-friendly, natural alternatives and emphasizes the role of parents, educators, and industry stakeholders in promoting safer practices. By addressing these concerns and fostering sustainable habits, we can protect the health and well-being of future generations while encouraging age-appropriate self-care.

Involving degradation products provides a new perspective of diffuse pollution assessment of atrazine with a modified mass balance approach.

Atrazine (ATR) is an endocrine disruptor known for its persistence and mobility. While the diffuse characteristics and potential risks of ATR have been extensively studied, its transregional migration and degradation characteristics have received less attention. In this study, a modified mass balance approach considering the diffuse source (DS), tributaries, water resource usage, degradation, adsorption, and evaporation was developed based on the traditional mass balance framework and field sampling to estimate the DS fluxes of ATR in a large river basin. Field sampling revealed that the ATR concentration in the surface water increased downstream, whereas the ATR levels in suspended particulate matter decreased. The ATR degradation ratio also decreased downstream, suggesting increased input along the river. The modified mass balance approach identified DS as the primary ATR source in the river, followed by tributaries. Together, the DS input and tributary inflow accounted for 95.6 % ± 2.1 % of the total ATR flux, with DS alone contributing 73.8 % ± 10.2 %. Finally, the ATR parent and its hazardous materials (ATR, desethylatrazine, and desisopropylatrazine) accounted for 6 % and 27 %, respectively, of the total ATR content that reached the estuary. This integrated consideration of ATR and its degradation products offer a new perspective on their transregional migration and degradation patterns resulting from diffuse pollution.

Transcriptomic Analysis of Effects of Developmental PCB Exposure in the Hypothalamus of Female Rats.

This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these phenotypes. We used 3' targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.

Quantifying microplastics concentration of invertebrates from three Antarctic fjords.

Microplastics, small pieces of plastic measuring less than five millimeters, have spread to all ecosystems, even those in the Southern Ocean around Antarctica. In particular, microplastics have been found contaminating water in emerging fjords, or inlets created by deglaciation, along the Antarctic Peninsula. Microplastics contamination puts fjord communities, which are unique and dominated by benthic species, at high risk for microplastic exposure leading to issues with feeding, endocrine disruption, and exposure to adsorbed toxins, all of which lower fecundity and survivability. The objective of this study was to quantify microplastics in invertebrates grouped according to feeding type. Invertebrates were collected from the Western Antarctic Peninsula fjords during 2017 and 2020 from three fjords via a mini-Agassiz trawl to quantify microplastic concentrations and identify polymer composition using Micro-ATR-FTIR. In 2017, 2.39 microplastics individual-1 were identified, while 5.01 microplastics individual-1 were identified in 2020. Out of the 24 polymers and polymer associates identified, the most common polymers were polypropylene, polycarbonate, polyamide, and polystyrene. Overall, the most common microplastic color category was black/brown/gblay, and fragments were the most common shape identified. Microplastics presence was significantly higher in the invertebrate organisms compared to procedural blanks (p<0.001), but feeding mechanism was not found to be a predictor of microplastic bioaccumulation. Microplastics concentrations in invertebrates differed between fjords in 2017 (p=0.010) but not in 2020. Complementing previous research on microplastics in Southern Ocean fjordic water, this study reveals new evidence of microplastics in Antarctic fjordic inhabitants.

High-Throughput Effect-Directed Analysis of Androgenic Compounds in Hospital Wastewater: Identifying Effect Drivers through Non-Target Screening Supported by Toxicity Prediction.

The increasing number of contaminants released into the environment necessitates innovative strategies for their detection and identification, particularly in complex environmental matrices like hospital wastewater. Hospital effluents contain both natural and synthetic hormones that might significantly contribute to endocrine disruption in aquatic ecosystems. In this study, HT-EDA has been implemented to identify the main effect-drivers (testosterone, androsterone and norgestrel) from hospital effluent using microplate fractionation, the AR-CALUX bioassay and an efficient data processing workflow. Through nontargeted screening, over 5000 features (ESI+) were initially detected, but our workflow's prioritization based on androgenic activity prediction reduced the number of features requiring further analysis by over 95%, significantly streamlining the workload. In addition, the semiquantitative nontarget analysis allowed for the calculation of the contribution of an identified compound to the total activity of the sample without the need for reference standards. While this contribution was low (∼4.3%) and applicable to only one compound (1,4-androstadiene-3,17-dione), it presents the first approach for calculating such contributions without relying on standards. Compared to the available alternatives our workflow demonstrates clear environmental relevance by enhancing HT-EDA for more efficient identification and prioritization of effect-drivers in hospital effluents, and it can be adapted to address other environmental threats in complex mixtures.

Predicting in vivo concentrations of dietary hop phytoestrogens by physiologically based kinetic modeling.

Hop extracts containing prenylated polyphenols such as 8-prenylnaringenin (8-PN) and its precursor isoxanthohumol (iXN) are popular among women seeking natural alternatives to hormone therapy for postmenopausal symptoms. Due to structural similarities with estrogens, these compounds act as estrogen receptor agonists. Especially 8-PN, described as the most potent phytoestrogen known to date, poses a potential risk for endocrine disruption. Therefore, its use as a hormone replacement raises concerns for human health. However, a significant challenge in assessing the potential endocrine-disruptive effects of hop polyphenols is the lack of data on their toxicokinetics. Particularly, information on in vivo concentrations in target tissues is lacking. To address this gap, we developed a physiologically based kinetic (PBK) model tailored to female physiology. The model was used to predict the levels of hop polyphenols in human blood and target tissues under realistic exposure scenarios. The predictions suggest that iXN and 8-PN concentrations in target tissues reach the low nanomolar range after dietary supplementation. This study enhances our understanding of internal concentrations of iXN and 8-PN after dietary consumption and is of direct applicability for respective risk assessment.

Trends, challenges, and research pathways in emerging contaminants: a comprehensive bibliometric analysis.

The growing concern over environmental pollution has spurred extensive research into various contaminants impacting ecosystems and human health. Emerging contaminants (ECs), including pharmaceuticals, personal care products, endocrine-disrupting chemicals, nanomaterials, and microplastics, have garnered significant attention due to their persistence, bioaccumulation, and toxicity. This study presents a comprehensive bibliometric analysis of EC research, aiming to detail the research landscape, highlight significant contributions, and identify influential researchers and pivotal studies. Data were sourced from the Web of Science, encompassing 62,670 documents from January 2000 to May 2024. Advanced bibliometric tools, including Bibliometrix, VOSviewer, and CiteSpace, were employed to analyze publication outputs, citation metrics, and collaboration patterns. The analysis revealed an exponential increase in EC research, with annual publications growing from fewer than 1,000 before 2006 to nearly 7,000 by 2022. Environmental Science & Technology emerged as the most influential journal. Based on the number of publications and citations as a country, China and the United States led in research outputs. Co-authorship and collaboration networks highlighted key hubs and prominent researchers, with significant contributions from environmental sciences, chemical engineering, and toxicology. Keyword co-occurrence analysis identified core themes, such as degradation, removal, and the impacts of ECs, reflecting evolving research interests and emerging topics. This bibliometric analysis provides valuable insights into the development and current state of EC research, serving as a resource for guiding future research efforts and fostering collaborations. The study indicates the critical need for continued research to address the challenges posed by ECs and develop effective regulatory policies and remediation strategies.

Single-cell RNA-seq reveals that granulosa cells are a target of phthalate toxicity in the ovary

Abstract Phthalates are known endocrine-disrupting chemicals and ovarian toxicants that are used widely in consumer products. Phthalates have been shown to exert ovarian toxicity on multiple endpoints, altering transcription of genes responsible for normal ovarian function. However, the molecular mechanisms by which phthalates act on the ovary are not well understood. In this study, we hypothesized that phthalates specifically target granulosa cells within the ovarian follicle. To test our hypothesis, we cultured whole mouse antral follicles for 96 h in the presence of vehicle or 10 µg/ml of a phthalate metabolite mixture. At the end of the culture period, follicles were dissociated into single-cell suspensions and subjected to single-cell RNA-sequencing. We used markers from published studies to identify cell-type clusters, the largest of which were granulosa and theca/stroma cells. We further identified subpopulations of granulosa, theca, and stromal cells and analyzed differentially expressed genes between the phthalate treatment and control. Granulosa cells, specifically mural granulosa cells, had the most differentially expressed genes. Pathway analysis of differentially expressed genes from the overall granulosa cell cluster revealed disruption of cell cycle and mitosis, whereas pathway analysis of the mural granulosa cell subcluster identified terms related to translation, ribosome, and endoplasmic reticulum. Our findings suggest that phthalates have both broad impacts on cell types and specific impacts on cellular subtypes, emphasizing the complexity of phthalate toxicity and highlighting how bulk sequencing can mask effects on vulnerable cell types.

Impact of Endocrine Disruptors on Key Events of Hepatic Steatosis in HepG2 Cells.

Endocrine-disrupting compounds (EDCs) may contribute to the rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the potential of 10 environmentally relevant EDCs to affect key events of hepatic steatosis in HepG2 human hepatoma cells. Increased lipid droplet formation, a key marker of steatosis, was induced by PFOA, bisphenol F, DDE, butylparaben, and DEHP, within the non-cytotoxic concentration range of 1 nM-25 μM. Cadmium also induced this effect, but at concentrations impairing cell viability (>1 μM). At non-cytotoxic concentrations, these compounds, along with bisphenol A, dysregulated major genes controlling lipid homeostasis. Cadmium, PFOA, DDE, and DEHP significantly upregulated the DGAT1 gene involved in triglyceride synthesis, while butylparaben increased the expression of the FAT/CD36 gene responsible for fatty acid uptake. Bisphenol A downregulated the CPT1A gene involved in fatty acid oxidation. No significant effects on lipid droplet accumulation or lipid metabolism-related genes were observed for PFOS, bisphenol S, and dibutyl phthalate. Among the tested EDCs, lipid accumulation positively correlated with the expression of SREBF1, DGAT1, and CPT1A. These findings provide additional evidence that EDCs can affect MASLD and highlight the utility of in vitro methods in the screening of EDCs with hazardous steatogenic and metabolism-disrupting properties.

Analyzing the potential targets and mechanisms of chronic kidney disease induced by common synthetic Endocrine Disrupting Compounds (EDCs) in Chinese surface water environment using network toxicology and molecular docking techniques.

Long-term exposure to NP and OP, as common synthetic endocrine-disrupting chemicals (EDCs) in surface water environments in China, is closely associated with the development of chronic kidney disease (CKD). However, their potential targets and toxicological mechanisms for inducing CKD remain unknown. This study utilizes network toxicology and molecular docking techniques to explore the potential toxic targets and molecular mechanisms of CKD induction by NP and OP. We identify 49 core targets of NP and OP action in CKD using the Comparative Toxicogenomics Database (CTD) and GeneCards databases. Using the STRING database and Cytoscape software, we identify five hub genes: MAPK3, TNF, BCL2, ESR1, and FOS. We construct a nomogram model based on the CKD dataset GSE66494, utilizing these five hub genes. Calibration and ROC curves demonstrate that the model has good diagnostic value for CKD, and the DCA curve indicates that the model has high clinical utility. Single-gene GSEA enrichment analysis identifies five hub genes that influence the development of CKD through multiple biological pathways, revealing that several immune-regulatory signaling pathways are activated. The CIBERSORT algorithm identifies eight types of immune cell infiltration levels that change significantly during CKD development, and correlation analyses suggest that the five hub genes are strongly associated with multiple immune cell infiltrations. The molecular docking results suggested that ESR1, MAPK3, and TNF had the lowest binding energies and high binding affinities with NP and OP. The results of molecular dynamics simulations similarly confirmed the stability of the interactions between ESR1, MAPK3 and TNF proteins with NP and OP. The results of this study provide a theoretical basis for understanding the potential toxicity targets and mechanisms of NP- and OP-induced CKD and promote the application of network toxicology and molecular docking techniques in the study of environmental pollutants.

Endocrine-disrupting compounds in urban rivers of the southern border of Mexico: Occurrence and ecological risk assessment

The occurrence of seven endocrine-disrupting compounds (EDCs) in four urban rivers on the southern border of Mexico was studied in this work. The selected EDCs were 17β-estradiol (E2), estriol (E3), 17α-ethinylestradiol (EE2), bisphenol A (BPA), bisphenol F (BPF), 4-nonylphenol (4NP) and 4-tert-octylphenol (4TOP). Water samples from the Coatan, Texcuyuapan, Cahoacan, and Coatancito rivers were collected at three different sites on each river and processed by solid phase extraction (SPE). The samples were analyzed by gas chromatography triple quadrupole tandem mass spectrometry (GC-MS/MS) and compounds of interest were identified by dynamic mass reaction monitoring mode (dMRM). Among the target EDCs, E2, BPA, and 4NP were detected in all water samples, with BPA being the most abundant ranging from 4.22 up to 127.96 ng/L. Correlation tests showed significant positive associations between estrogens and BPA, as well as the correlation between alkylphenols and BPA, suggesting common origin emission sources, which were identified as discharges of untreated municipal wastewater. Finally, the estimation of RQ and EEQ values indicated that the presence of E2, E3, EE2, and BPA in all sampled points represents a high risk for aquatic life in these sites, mainly for Texcuyuapan River, where the aquatic organisms may be susceptible to endocrine disruption by chronic exposure to detected compounds.

Association Between Endocrine-Disrupting Chemicals Exposure and Attention-Deficit/Hyperactivity Disorder Symptoms in Children With Attention-Deficit/Hyperactivity Disorder.

This study investigated the relationship between exposure to endocrine-disrupting chemicals (EDCs), specifically phthalates, bisphenol A, bisphenol F, and bisphenol S, and the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms using neuropsychological tests in children diagnosed with ADHD. This study included 67 medication-naïve children with ADHD aged 6-16 years. The urinary concentrations of EDCs were measured, and ADHD symptom severity was evaluated using neuropsychological tests and clinical symptom scale measurements. The Jonckheere-Terpstra test, Pearson and Spearman correlation analyses, linear regression models, and multiple regression models were used to examine the relationship between EDC exposure and ADHD symptoms. A significant correlation was observed between urinary phthalate metabolite concentrations and commission error T-scores in the visual Advanced Test of Attention test. No significant associations were found with other neuropsychological indicators or bisphenol levels. Phthalate exposure affects impulsivity in children with ADHD, which is consistent with the results of previous studies that used parental surveys. However, bisphenols are not clearly associated with ADHD symptoms, which is consistent with the results of previous studies.

A three-dimensional mouse liver organoid platform for assessing EDCs metabolites simulating liver metabolism.

Hepatic metabolism is an important process for evaluate the potential activity and toxicity of endocrine disrupting chemicals (EDCs) metabolites. Organization for Economic Co-operation and Development (OECD) has advocated the development of in vitro assays that mimic in vivo hepatic metabolism to eventually replace classical animal tests. In response to this need, we established a 3D mouse liver organoid (mLO) platform that mimics the animal model and is distinct from existing models. We evaluated the effects the activity of EDC metabolites generated through mLOs based on human cell-based reporter gene assays in addition to existing models. This study emphasizes the importance of hepatic ex-vivo and suggests the need a new metabolic model through a 3D mLOs platform. These results indicate that mLOs provides a novel biological method to screen for potential endocrine-disrupting activities of EDC metabolites.

AMAZON ACAI AND PINEAPPLE RESIDUES INDUCE THE ENZYME LACCASE IN Pleurotus ostreatus: APPLICATION TO BISPHENOL A BIOREMEDIATION

Bisphenol A (BPA), an endocrine disruptor used in different commercial polymers, is a persistent pollutant commonly found in effluents. Conventional wastewater treatment processes have low chemical removal efficiency and are expensive. This work evaluated BPA removal using laccase enzyme produced from white rot fungus Pleurotus ostreatus. For the enzymatic production, residues of acai berry and pineapple were used as laccase inducers. The use of natural inducers led to a high enzyme production (1139 and 1031 U mL-1 to acai and pineapple, respectively). Bisphenol A was removed to a concentration lower than LOD (limit of detection) after 4 h. The degradation mechanism of BPA occurred by oxidation of methyl to hydroxymethyl group in a propane portion, with breakdown of the aromatic ring. The developed technology brought to the scene a new green, viable methodology, using vegetable waste, adding value to these residues and bringing an alternative to the BPA treatment.

3-methyl-4-nitrophenol disturbs the maternal-to-zygotic transition of early embryos by damaging mitochondrial function and histone modification.

3-methyl-4-nitrophenol (PNMC), a chemical prevalent in various industries for drug, dye, and leather production, also serves as a primary byproduct of organophosphate insecticides. Despite its global recognition as an endocrine disruptor with documented reproductive toxicity, its detrimental impact on preimplantation embryonic development has yet to be thoroughly investigated. In this study, through the in vitro culture of mice embryos, it was initially observed that even low concentrations of PNMC exposure led to a significant reduction in blastocyst formation and a sharp decline in the ratio of inner cell mass within the blastocysts. SMART-seq2 transcriptome sequencing further confirmed that PNMC treatment disrupted global gene expression in 2-cell embryos, with differentially expressed genes enriched in multiple signaling pathways, including those related to autophagy, apoptosis, fertilization, embryonic development, transcription, and mRNA processing. Integration of transcriptome data with open databases revealed that both zygotic genome activation genes and maternal factors experienced significant transcript-level disruptions. Moreover, the study demonstrated that these gene expression changes were closely associated with mitochondrial dysfunction, evidenced by diminished mitochondrial membrane potential, reduced ATP production, aberrant expression of mitochondria-related genes, increased ROS accumulation, and heightened DNA damage in PNMC-treated embryos. Additionally, PNMC exposure induced defects in histone modification, as shown by altered levels of H3K9me3 and H3K27me3, H3K9ac and H3K27ac. Lastly, the findings indicated that PNMC triggered apoptosis in embryos, validated by elevated BAX and CASPASE3 expression, alongside positive TUNEL staining. In summary, PNMC exposure impairs the maternal-to-zygotic transition, likely through mitochondrial dysfunction and histone modification, culminating in developmental arrest and apoptosis in mouse preimplantation embryos.