Environmental Endocrine Disruptors Research Articles

The Potential Relationship Between Environmental Endocrine Disruptor Exposure and the Development of Endometriosis and Adenomyosis.

Women with endometriosis, the growth of endometrial glands and stroma outside the uterus, commonly also exhibit adenomyosis, the growth of endometrial tissues within the uterine muscle. Each disease is associated with functional alterations in the eutopic endometrium frequently leading to pain, reduced fertility, and an increased risk of adverse pregnancy outcomes. Although the precise etiology of either disease is poorly understood, evidence suggests that the presence of endometriosis may be a contributing factor to the subsequent development of adenomyosis as a consequence of an altered, systemic inflammatory response. Herein, we will discuss the potential role of exposure to environmental toxicants with endocrine disrupting capabilities in the pathogenesis of both endometriosis and adenomyosis. Numerous epidemiology and experimental studies support a role for environmental endocrine disrupting chemicals (EDCs) in the development of endometriosis; however, only a few studies have examined the potential relationship between toxicant exposures and the risk of adenomyosis. Nevertheless, since women with endometriosis are also frequently found to have adenomyosis, discussion of EDC exposure and development of each of these diseases is relevant. We will discuss the potential mechanisms by which EDCs may act to promote the co-development of endometriosis and adenomyosis. Understanding the disease-promoting mechanisms of environmental toxicants related to endometriosis and adenomyosis is paramount to designing more effective treatment(s) and preventative strategies.

Environmental endocrine disruptor concentrations in urine samples from Mexican Indigenous women

The Indigenous communities in Mexico show significant degrees of vulnerability to pollution due to the lack of knowledge of health risks, traditions, low levels of support, and restricted access to healthcare. As a result, exposure to environmental endocrine disruptors increases in these populations through plastic components or indoor air pollution. Therefore, the aim of the study was to evaluate the exposure to phthalate metabolites, 1-hydroxypyrene, and bisphenol A through biomonitoring data from indigenous Mexican women. A total of 45 women from the Tocoy community in San Luis Potosí, Mexico, were included. Urine samples were analyzed for Bisphenol Aand 4 phthalate metabolites by ultra-performance liquid chromatography couples to tandem mass spectrometry; additionally, the 1-hydroxypyrene concentrations were evaluated by high-performance liquid chromatography coupled to a fluorescence detector. Among the main pollution sources were the use of plastic containers and burning garbage (98-100%). Indigenous women presented an exposure of 100% to mono-2-ethyl phthalate, mono-n-butyl phthalate, and 1-hydroxypyrene, with a median (25th-75th percentiles) of 17,478 (11,362-37,355), 113.8 (61.7-203.5), and 1.2 (0.9-1.7) µg/g creatinine, respectively. The major findings show urinary mono-2-ethyl phthalate concentrations higher than those measured from other studies. Therefore, these results show an impressive exposure to di(2-ethylhexyl) phthalate in Indigenous women. The current study reflects the absence of regulatory policies in marginalized populations. It highlights the need to design strategies that mitigate exposure and the importance of biological monitoring to evaluate and prevent health risk associated with exposure to environmental endocrine disruptors.

Endocrine disruption from plastic pollution and warming interact to increase the energetic cost of growth in a fish.

Energetic cost of growth determines how much food-derived energy is needed to produce a given amount of new biomass and thereby influences energy transduction between trophic levels. Growth and development are regulated by hormones and are therefore sensitive to changes in temperature and environmental endocrine disruption. Here, we show that the endocrine disruptor bisphenol A (BPA) at an environmentally relevant concentration (10 µgl-1) decreased fish (Danio rerio) size at 30°C water temperature. Under the same conditions, it significantly increased metabolic rates and the energetic cost of growth across development. By contrast, BPA decreased the cost of growth at cooler temperatures (24°C). BPA-mediated changes in cost of growth were not associated with mitochondrial efficiency (P/O ratios (i.e. adenosine diphosphate (ADP) used/oxygen consumed) and respiratory control ratios) although BPA did increase mitochondrial proton leak. In females, BPA decreased age at maturity at 24°C but increased it at 30°C, and it decreased the gonadosomatic index suggesting reduced investment into reproduction. Our data reveal a potentially serious emerging problem: increasing water temperatures resulting from climate warming together with endocrine disruption from plastic pollution can impact animal growth efficiency, and hence the dynamics and resilience of animal populations and the services these provide.

Innovative preparation of ureido/dodecyl dual-functionalized silica as a versatile mixed-mode stationary phase for high-resolution chromatographic separations

Developing a versatile stationary phase to achieve the purpose of efficiently separating various target analytes is of great significance. In this work, ureido/dodecyl dual-functionalized silica (Sil-Ur-DD) was synthesized and employed as a new mixed-mode stationary phase for high-resolution chromatographic analysis. It was observed that multiple interactions, including hydrophobic, hydrophilic, hydrogen bonding, electrostatic and π-π interactions, contributed to the retention. Nucleosides and nucleobases could be effectively determined in hydrophilic interaction chromatography mode, and the separation performance of the Sil-Ur-DD was found to be even superior to that of the commercial XAmide column. Environmental endocrine disruptors, including alkylphenols, bisphenols, steroid hormones and phthalates, were more favorably separated in reversed-phase chromatography mode with highly aqueous mobile phases compared with the commercial C18-silica column. The experimental results indicated that the combined effect of ureido and long-chain alkyl groups obviously enhanced separation efficiency and selectivity. More significantly, the proposed method concerning the preparation of an efficient separation material with powerful separation ability is economical and environmentally friendly, which provides a proven and effective way for the recycling and utilization of the discarded chromatographic packing materials, thereby showing a good application prospect.

Differential Expression Profiles and Potential Intergenerational Functions of tRNA-Derived Small RNAs in Mice After Cadmium Exposure

Cadmium (Cd) is a toxic heavy metal and ubiquitous environmental endocrine disruptor. Previous studies on Cd-induced damage to male fertility mainly focus on the structure and function of testis, including cytoskeleton, blood-testis barrier, and steroidogenesis. Nevertheless, to date, no studies have investigated the effects of Cd exposure on sperm epigenetic inheritance and intergenerational inheritance. In our study, we systematically revealed the changes in sperm tRNA-derived small RNAs (tsRNA) profiles and found that 14 tsRNAs (9 up-regulated and 5 down-regulated) were significantly altered after Cd exposure. Bioinformatics of tsRNA-mRNA-pathway interactions revealed that the altered biological functions mainly were related to ion transmembrane transport, lipid metabolism and cell membrane system. In addition, we focused on two stages of early embryo development and selected two organs to study the impact of these changes on cell membrane system, especially mitochondrion and lysosome, two typical membrane-enclosed organelles. Surprisingly, we found that the content of mitochondrion was significantly decreased in 2-cell stage, whereas remarkably increased in the morula stage. The contents of mitochondrion and lysosome were increased in the testes of 6-day-old offspring and livers of adult offspring, whereas remarkably decreased in the testes of adult offspring. This provides a possible basis to further explore the effects of paternal Cd exposure on offspring health.

Exposure to nonylphenol impairs oocyte quality via the induction of organelle defects in mice

Nonylphenol (NP) is an environmental endocrine disruptor, which is mainly used in the production of surfactants, lubricants, additives, pesticides, and emulsifiers. NP is widely found in sewage and sludge, which has neurotoxicity, immunotoxicity, metabolic toxicity and reproductive toxicity. In this study, we investigated the effects of NP exposure on mammalian oocyte quality from organelle aspects with mouse in vivo model. The results showed that the ovarian weight of mice exposed to 500 μg/L NP for 4 weeks increased and the development ability of oocytes decreased, showing with lower rate of polar body extrusion. Further analysis indicated that exposure to NP caused the abnormal distribution of mitochondria, following with altered membrane potential drop. NP exposure disrupted the spindle periphery localization of ER, and affected the expression of GRP78 for the induction of ER stress. Moreover, Golgi apparatus fragment in the oocytes was observed, and Rab11-based vesicle transport was disturbed. We also found that the protein degradation might be affected since LAMP2 expression increased and LC3 decreased, indicating the lysosome and autophagy dysfunction. Taken together, our findings suggested that the exposure of NP to mice in vivo affected oocyte quality through its effects on the distribution and function of organelles.

Gestational bisphenol A exposure impairs hepatic lipid metabolism by altering mTOR/CRTC2/SREBP1 in male rat offspring.

Lipid metabolism is an important biochemical process in the body. Recent studies have found that environmental endocrine disruptors play an important role in the regulation of lipid metabolism. Bisphenol A (BPA), a common environmental endocrine disruptor, has adverse effects on lipid metabolism, but the mechanism is still unclear. This study aimed to investigate the effects of gestational BPA exposure on hepatic lipid metabolism and its possible mechanism in male offspring. The pregnant Sprague-Dawley rats were exposed to BPA (0, 0.05, 0.5, 5mg/kg/day) from day 5 to day 19 of gestation to investigate the levels of triglyceride (TG) and total cholesterol (TC), and the expression of liver lipid metabolism-related genes in male offspring rats. The results showed that compared with the control group, the TG and TC levels in serum and liver in BPA-exposed groups was increased. And the expressions of liver fatty acid oxidation related genes, such as peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase 1α (CPT1α), were down-regulated. However, the expressions of fatty acid synthesis related genes, such as sterol regulatory element binding proteins 1 (SREBP-1), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1), were up-regulated. The increased protein levels of mTOR and p-CRTC2 suggested that CREB-regulated transcription coactivator 2 (CRTC2) might be an important mediator in the mTOR/SREBP-1 pathway. In conclusion, these results demonstrated that mTOR/CRTC2/SREBP-1 could be affected by gestational BPA exposure, which may involve in the lipid metabolic disorders in later life.

Effect of Vitamins C and E On Nonylphenol–Induced Dna Damage and Tefu Gene Expression in Drosophila Melanogaster

:Nonylphenol (NP) is one of the major environmental endocrine disrupters that can cause oxidative damage. Vitamin C (ascorbic acid) and vitamin E (α-tocopherol) are powerful antioxidants that could offset the effects of NP and are compounds that should be taken daily. In this study, the potential effects of the separate and combined administration of NP (1 and 10 mg/L) and vitamins C and E (25 mg/L) on DNA damage and telomere fusion (TEFU) gene expression in Drosophila melanogaster, a model organism, were investigated over 40 days. For the NP-administered groups, DNA damage increased while vitamins C and E reduced these effects, especially those induced by a co-administered group of NP and vitamin E. Furthermore, telomerase and DNA damage-associated TEFU gene expression levels increased in the NP-administered groups compared to the control group, while they decreased in the vitamin C and E administered groups. Consequently, it was concluded that vitamin C and E prevents the negative effects of NP on DNA damage.

Bisphenol A induces apoptosis and autophagy in murine osteocytes MLO-Y4: Involvement of ROS-mediated mTOR/ULK1 pathway

Bisphenol A (BPA) is a widely environmental endocrine disruptor. The accumulated BPA in humans is toxic to osteoblasts and osteoclasts, but few studies focused on the effects of BPA on osteocytes, the most abundant bone cell type, contributing to the development and metabolism of bone. Here, we reported that BPA (50, 100, 200 μmol/L) inhibited the cell viability of osteocytes MLO-Y4, promoted G0/G1 phase arrest and apoptosis in a dose-dependent manner. BPA treatment significantly increased the levels of autophagy-regulated proteins including Beclin-1 and LC3-II along with the decrease of p62, accompanied by the elevation of autophagy flux and the accumulation of acidic vacuoles, which was blocked by the autophagy inhibitor bafilomycin A1 (BafA1). Furthermore, BPA significantly inhibited the mammalian target of rapamycin (mTOR) and activated Unc-51 like autophagy activating kinase 1 (ULK1) signaling, leading to the decreased p-mTOR/mTOR ratio and the increased p-ULK1/ULK1 ratio. The mTOR activator MHY1485 (MHY) or the ULK1 inhibitor SBI-0206965 (SBI) prevented autophagy and enhanced apoptosis caused by BPA, respectively. In addition, BPA increased the levels of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and decreased antioxidant enzymes nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) levels, resulting in oxidative stress. The ROS scavenger N-acetylcysteine (NAC) attenuated BPA-induced the mTOR/ULK1 pathway activation, apoptosis and autophagy. Collectively, ROS-mediated mTOR/ULK1 signaling is involved in BPA-induced apoptosis and autophagy in osteocytes MLO-Y4. Our data first provide in vitro evidence that apoptosis and autophagy as cellular mechanisms for the toxic effect of BPA on osteocytes, thereby advancing our understanding of the potential role of osteocytes in the adverse effect of BPA on bone health.

Effects of an environmental endocrine disruptor, para-nonylphenol on the cell growth of Euglena gracilis: association with the cellular oxidative stress.

Effects of an environmental endocrine disruptor, para-nonylphenol (NP) on the cell growth of a photosynthetic eukaryotic microorganism, Euglena gracilis were analysed under different cell culture conditions. Although NP did not show significant inhibitory effects on the cell growth of E. gracilis (Z and SM strains) under light culture condition, NP exhibited significant suppressive effects under dark culture condition. Exogenous supplementation with lipophilic antioxidants (α-tocopherol, β-carotene or 6-O-palmitoyl-ascorbic acid) to E. gracilis caused strong preventive effects against NP-induced cell growth inhibition under dark culture condition, but hydrophilic antioxidants [ascorbic acid, glutathione and epigallocatechin gallate (EGCG)] did not show significant preventive effects. NP caused significant generation of reactive oxygen species (ROS) in E. gracilis under dark culture condition, but E. gracilis under light culture condition did not show significant increase in ROS generation. Supplementation with lipophilic antioxidants to E. gracilis caused significant suppressive effects against NP-induced cellular ROS generation under dark culture condition, but hydrophilic antioxidants did not show significant suppressive effects. Furthermore, the productivities of typical cellular antioxidants (α-tocopherol, β-carotene and ascorbic acid) in E. gracilis under light culture conditions were much higher than those under dark culture conditions.

Combined effect of unfolded protein response and circZc3h4, circRNA Scar in mouse ovary and uterus damage induced by procymidone

Procymidone (PCM) is a fungicide commonly used to prevent and control plant diseases, and it is also an environmental endocrine disruptor that has a typical anti-androgen effect on the function and/or structure of the vertebrate reproductive system. The activation of the unfolded protein response (UPR) will fold the protein correctly to ensure the cell’s survival. PCM regulates GRP78 by affecting the level of hormones, and there is a regulatory relationship between the UPR, the circRNAs and the miRNAs. In vivo experiments, PCM (suspended in soybean oil) was orally administered to adolescent female mice for 21 days in 3 different doses of 50 mg kg–1 day–1 (low dose), 100 mg kg–1 day–1 (medium dose) and 200 mg kg–1 day–1 (high dose) to cause ovaries and uteruses damage, and in vitro experiments, various doses of PCM from 0.33 × 10−5 (low dose) to 1 × 10−5 (medium dose) then 3 × 10−5 M (high dose) were used to induce injury on the ovaries and uteri of the mice. We found out that both in vivo and in vitro, PCM caused dose-dependent damages to the ovaries and uteri, increased their circRNA Scar levels and decreased circZc3h4 abundance. Also, all UPR signaling pathways in the low-dose group and some in the middle-dose group were activated. It is speculated that UPR may antagonize the partial ovarian and uterine damage in adolescent mice induced by PCM at doses less than NOAEL via changes in circZc3h4 and circRNA Scar.

Associations between endocrine-disrupting heavy metals in maternal hair and gestational diabetes mellitus: A nested case-control study in China.

Exposure to environmental endocrine disruptors (EDCs) may lead to abnormal glucose metabolism and, potentially, gestational diabetes mellitus (GDM). We investigated the association between five endocrine-disrupting heavy metals (EDHMs), i.e., arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), and tin (Sn), in maternal hair and the risk of GDM. We conducted a nested case-control study including 335 GDM cases and 343 controls without GDM based on a prospective birth cohort established in Beijing, China. Concentrations of EDHMs were analyzed in maternal hair. Log-binomial regression and multiple linear regression were used to estimate the associations between the hair concentrations of single metals and the risk of GDM, while weighted quantile sum (WQS) regression for their mixed effects. The median concentrations of Hg (0.442 vs. 0.403μg/g) and Sn (0.171 vs. 0.140μg/g) in the case group were significantly higher than those in the control group. No differences were found between the two groups for the other three metals. After adjusting for confounders, the prevalence ratio (PR; highest vs. lowest tertile) of GDM risk for Hg was 1.27 (95% confidence interval [CI]: 1.05-1.54), while that for Sn was 1.26 (95% CI: 1.04-1.53). Among women with a body mass index<24kg/m2, the PR (highest vs. lowest tertile) of GDM for Sn was 1.38 (95% CI: 1.09-1.75). The effect of exposure to the five EDHMs on the risk of GDM was estimated by WQS regression: Sn and Hg made the largest contributions to the WQS index (40.9% and 40.3%, respectively). High maternal levels of EDHMs, particularly Sn and Hg, may promote the development of GDM.

Prokaryotic expression of human-sourced and zebrafish-sourced protein kinase A alpha catalytic subunits combined with in vitro and in silico assay

The extensively studied cAMP-dependent protein kinase A (PKA) is involved in the regulation of critical cell processes, including metabolism, gene expression, and cell proliferation. Therefore, PKA has been viewed increasingly as potential target for variety of drugs and environmental endocrine disruptors. Consequentially, the preparation of PKA protein became an important initial step for the subsequent exploration of PKA’s character in endocrine disrupting effects of pesticides. To investigate PKA protein, which is potential to be the environmental endocrine toxicity target of triazole fungicides, a strategy to heterologously express protein kinase A catalytic alpha subunit of human (hPKAcα) and zebrafish (zPKAcα) in Escherichia coli (E. coli) BL21(DE3) host cells was demonstrated. After optimizing conditions and protein purification, we successfully obtained enzymatically active hPKAcα and zPKAcα. Western blot analysis indicated that the recombinant hPKAcα and zPKAcα still retained their characteristic antigenicity and binding activity, while in vitro kinase activity assays revealed that the recombinant hPKAcα and zPKAcα maintained enzyme activity. By in silico methods including homology modelling and molecular docking, the affinity of ligands and the models of hPKAcα and zPKAcα were further tested. The present study offered a valuable method to achieve the prokaryotic expression of a eukaryotic protein kinase and laid a foundation to facilitate further investigation of toxicological target of triazole pesticides.

Highly-sensitive and simple fluorescent aptasensor for 17 b-estradiol detection coupled with HCR-HRP structure

As an important kind of environmental endocrine disruptors, 17 β -Estradiol (E2) plays a major role in affecting the growth of human including sexual characters, pregnancy system, etc. In the modern society, with the threat of abuse in breeding, it is imperative to design sensitive methods for detecting low concentration of E2 in environment. In this work, we constructed a highly sensitive and simple fluorescent aptasenor for detecting E2 via amplification of hybridization chain reaction (HCR) and horseradish peroxidase (HRP). Through the competitions between complementary strand (cmDNA) and E2 to E2 aptamer modified on magnetic beads, the unbound cmDNA would be collected and captured by polystyrene microspheres to induce HCR which brought abundant biotin sites. Subsequently, benefit from the excellent catalytic performance of streptavidin-horseradish peroxidase (SA-HRP), the highly sensitive fluorescence signals could be obtained in low concentration of E2. Under the optimal conditions, the prospered method for E2 detection was shown a good liner range from 1 to 100 pg/mL, with the lower detecting limit of 0.2 pg/mL compared with previous work. In addition, the recovery rates tested in the real samples of milk and water were 99.20%–108.06% and 91.07%–106.13%. In all, the assay may provide a perspective way for highly sensitive detection for various contaminants in the real samples.

Bisphenol-A exposure leads to neurotoxicity through upregulating the expression of histone deacetylase 2 in vivo and in vitro

Bisphenol-A (BPA), an environmental endocrine disruptor, is toxic to the central nervous system. Although recent studies have shown BPA-induced neurotoxicity, it is far from clear what precisely epigenetic mechanisms are involved in BPA-induced cognitive deficits. In this study, pheochromocytoma (PC12) cells were treated with BPA at 1 μM for 36 h in vitro. In vivo, C57BL/6 mice were administered to BPA at a dose of 1 mg/kg/day for 10 weeks. The results showed that 1 μM BPA exposure for 36 h impaired neurite outgrowth of PC12 cells through decreasing the primary and secondary branches. Besides, BPA exposure decreased the level of Ac-H3K9 (histone H3 Lys9 acetylation) by upregulating the expression of HDAC2 (histone deacetylases 2) in PC12 cells. Furthermore, treatment of both TSA (Trichostatin A, inhibitor of the histone deacetylase) and shHDAC2 plasmid (HDAC2 knockdown construct) resulted in amelioration neurite outgrowth deficits induced by BPA. In addition, it was shown that repression of HDAC2 could markedly rescue the spine density impairment in the hippocampus and prevent the cognitive impairment caused by BPA exposure in mice. Collectively, HDAC2 plays an essential role in BPA-induced neurotoxicity, which provides a potential molecular target for medical intervention.

Comprehensive analysis based in silico study of alternative bisphenols – Environmental explanation of prostate cancer progression

Industries have begun to shift their focus on exploring substitute chemicals for BPA due to their concerns about safety and environmental pollution. In recent years, alternative bisphenols, including BPS, BPF, and BPAF have been extensively used as BPA substitutes. Based on previous studies, BPA is considered a risk factor for prostate cancer. This work aims to explore the interactive genes related to alternative bisphenols and prostate cancer using the TCGA, CTD, and GEO databases. After performing the GO and KEGG enrichment analysis, a correlation between alternative bisphenols and prostate cancer was detected using bioinformatics analysis. Among the interactive genes of alternative bisphenols, ferroptosis-related genes revealed strong correlations with prostate cancer. Moreover, the prognostic predictive model, ROC curve, and survival analysis confirmed that ferroptosis-related genes displayed a strong correlation in the prognosis of prostate cancer. We successfully evaluated the relationship between prostate cancer and alternative bisphenols; as a result, a novel approach was proposed to explore the damaging effect of environmental endocrine disruptors.

Weighted gene coexpression network analysis reveals ESR1, FLNA and Furin as hub genes for DEHP-induced prepubertal testicular injury

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor that accumulates in organisms in various ways and induces male reproductive system disorders. In this study, we established a testicular injury model by gavage with different concentrations of DEHP. The testes were then collected for RNA sequencing (RNA-seq), and the results were analyzed by bioinformatics and verified by experiments. Our research results show that different concentrations of DEHP interfere with testicular development differently. Weighted gene coexpression network analysis (WGCNA) generated sixteen modules and identified the turquoise module as key. Then, estrogen receptor 1 (ESR1), filamin A (Flna) and Furin were identified as hub genes. qPCR and immunohistochemistry results revealed that all three hub genes were upregulated. We detected the locations of these genes by immunohistochemistry. ESR1 was mainly located in Leydig cells; Flna immunostaining is observed in the Leydig and some germ cells and Furin staining was seen in almost all types of testicular cells. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed enrichment mainly in MAPK signaling pathways, p53 signaling pathways, HIF-1 signaling pathways, protein processing in the endoplasmic reticulum, apoptosis, the cell cycle, RNA degradation, etc. This is the first study using WGCNA to investigate the mechanism of DEHP-induced injury in the prepubertal testis, providing new research angles to further understand the mechanism of DEHP-induced injury in the prepubertal testis.

Artificial intelligence to link environmental endocrine disruptors (EEDs) with bone diseases

Our endocrine system is not only complex, but is also enormously sensitive to the imbalances caused by the environmental stressors, extreme weather situation, and other geographical factors. The endocrine disruptions are associated with the bone diseases. Osteoporosis is a bone disorder that occurs when bone mineral density and bone mass decrease. It affects women and men of all races and ethnic groups, causing bone weakness and the risk of fractures. Environmental stresses are referred to physical, chemical, and biological factors that can impact species productivity. This research aims to examine the impact of environmental stresses on bone diseases like osteoporosis and low bone mass (LBM) in the United States (US). For this purpose, we use an artificial neural network model to evaluate the correlation between the data. A multilayer neural network model is constructed using the Levenberg–Marquardt training algorithm, and its performance is evaluated by mean absolute error and coefficient of correlation. The data of osteoporosis and LBM cases in the US are divided into three groups, including gender group, age group, and race/ethnicity group. Each group shows a positive correlation with environmental stresses and thus the endocrinology.

Cyanidin-3-O-glucoside ameliorates cadmium induced uterine epithelium proliferation in mice

Cadmium (Cd) is an environmental pollutant and endocrine disrupter, abundantly present in water, food, and soil. Accumulation of Cd in the body can negatively affect female reproduction; especially the uterus is exceptionally sensitive to the toxic actions of Cd. The anthocyanin cyanidin-3-O-glucoside (C3G) is a naturally occurring phenolic compound in fruits and plants that can antagonize the toxic effects of Cd. This capacity makes C3G a possible candidate to prevent Cd-induced female infertility. The present study aimed to investigate: 1) whether C3G intake could prevent Cd-induced female reproductive toxicity, and 2) the underlying mechanisms responsible for this protective effect. The results of our study indicated that Cd exposure did not affect ovarian function, but induced hypertrophy of the uterine endometrium. Oral intake of C3G markedly reduced the effects of Cd exposure on the thickness of the uterine epithelium cells. Transcriptomic analysis of the endometrium revealed that C3G intake had anti-estrogenic effects, attenuating Cd-induced endometrial epithelial cell proliferation by inhibiting estrogen-responsive genes, enhancing epithelial progesterone receptor expression, and regulating Klf4 expression. The current findings implicate that C3G has the potential to be used as a dietary supplement based on its capacity to intervene in Cd-induced female reproductive toxicity.

Effects of chronic triclosan exposure on social behaviors in adult mice

Triclosan (TCS), a newly identified environmental endocrine disruptor (EED) in household products, has been reported to have toxic effects on animals and humans. The effects of TCS exposure on individual social behaviors and the potential underlying mechanisms are still unknown. This study investigated the behavioral effects of 42-day exposure to TCS (0, 50, 100 mg/kg) in drinking water using the open field test (OFT), social dominance test (SDT), social interaction test (SIT), and novel object recognition task (NOR). Using 16S rRNA sequencing analysis and transmission electron microscopy (TEM), we observed the effects of TCS exposure on the gut microbiota and ultrastructure of hippocampal neurons and synapses. Behavioral results showed that chronic TCS exposure reduced the social dominance of male and female mice. TCS exposure also reduced social interaction in male mice and impaired memory formation in female mice. Analysis of the gut microbiota showed that TCS exposure increased the relative abundance of the Proteobacteria and Actinobacteria phyla in female mice. Ultrastructural analysis revealed that TCS exposure induced ultrastructural damage to hippocampal neurons and synapses. These findings suggest that TCS exposure may affect social behaviors, which may be caused by altered gut microbiota and impaired plasticity of hippocampal neurons and synapses.