Effects of postweaning cadmium exposure on socioemotional behaviors in adolescent male mice.

Exposure to cadmium (Cd), a toxic heavy metal classified as an environmental endocrine disruptor, can exert significant toxicity in both animals and humans. However, the potential effects of Cd exposure on socioemotional behaviors are still poorly understood, as are the underlying mechanisms. In the present study, employing a series of behavioral tests as well as 16 S rRNA sequencing analysis, we investigated the long-term effects of Cd exposure on socioemotional behaviors and their associated mechanisms in mice based on the brain-gut interaction theory. The results showed that postweaning exposure to Cd reduced the ability to resist depression, decreased social interaction, subtly altered sexual preference, and changed the composition of the gut microbiota in male mice during adolescence. These findings provided direct evidence for the deleterious effects of exposure to Cd in the postweaning period on socioemotional behaviors later in adolescence, and suggested that these effects of Cd exposure may be linked to changes in the gut microbiota.

Research progress on relationship between exposure to perfluoroalkyl and polyfluoroalkyl substances and allergic diseases / 环境与职业医学

Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a group of persistent organic pollutants among environmental endocrine disruptors, are widely used in industrial production and daily life. PFASs are widely and persistently present in the environment and organisms due to their bioaccumulation, long half-life, and low degradability properties. Published studies have proved that PFASs have immunotoxicity, endocrine toxicity, neurotoxicity, reproductive toxicity, and hepatotoxicity. At present, several epidemiological studies have been conducted on the effects of PFASs on allergic diseases, the research endpoints include asthma, allergic rhinitis, atopic dermatitis, and the expression of allergic biomarkers such as serum immunoglobulin E (IgE), but no consistent results have been observed yet. PFASs have the potential to activate several signaling pathways, including the peroxisome proliferator-activated receptor (PPAR), nuclear factor-κB (NF-κB), and JAK/STAT pathways. These mechanisms, along with increasing mast cell calcium influx and sex hormone synergistic effects, may contribute to immunomodulation in allergic diseases. At present, the exact human effect of PFASs exposure on allergic diseases and the related mechanisms are still uncertain. This review focused on the impacts of PFASs on asthma, allergic rhinitis, and atopic dermatitis and their possible mechanisms, so as to provide research ideas for the prevention, diagnosis, and treatment of allergic diseases.

Environmental polycyclic aromatic hydrocarbon exposure in relation to metabolic syndrome in US adults.

The present study examined the associations of polycyclic aromatic hydrocarbon (PAH) exposure with metabolic syndrome (MetS) and its components. Data were from 5181 US adults recruited in the National Health and Nutrition Examine Survey 2001-2012. Environmental PAH exposure was estimated as concentrations of urinary PAH metabolites. Weighted quantile sum (WQS) regression and modified Poisson regression were separately conducted to estimate the associations of mixed and single PAH metabolites with MetS and its components. WQS regression analyses showed that participants with higher mixed PAH exposure had increased prevalence of MetS (prevalence ratio, 1.12; 95 % confidence interval, 1.06, 1.19), elevated waist circumference (1.07; 1.02, 1.12), elevated fasting blood glucose (1.07; 1.00, 1.14), elevated triglycerides (1.19; 1.09, 1.30), and reduced high-density lipoprotein cholesterol (1.11; 1.03, 1.20). In the models for single PAH metabolites, higher levels of 1-hydroxynaphthalene (1.15; 1.00, 1.32), 2-hydroxynaphthalene (1.20; 1.05, 1.38), 1-hydroxyphenanthrene (1.18; 1.04, 1.34), 2-hydroxyphenanthrene (1.38; 1.22, 1.57), and 1-pyrene (1.19; 1.05, 1.34) were respectively associated with increased prevalence of MetS (highest tertile vs lowest tertile). In addition, linear trends were noted for the associations of these PAH metabolites with MetS (all P for linear association ≤0.047). Smokers, drinkers, and participants with poor diet quality showed stronger associations between certain PAH metabolite with MetS. The findings suggest that the prevalence of MetS and its components increases when PAH exposure is at a high level, and that lifestyle factors, such as cigarette smoking, alcohol consumption, and diet quality, could modify the positive associations of certain PAH exposure with MetS.

A preliminary study on the relationship between environmental endocrine disruptors and precocious puberty in girls.

OBJECTIVES: To explore the associations of environmental endocrine disruptors on precocious puberty in girls. METHODS: This was a case-control study in which 30 girls with precocious puberty and 46 age- and race-matched prepubertal females were enrolled. The concentrations of 10 environment endocrine disruptors (bisphenol A, bisphenol B, butylparaben, propylparaben, ethvlparaben, methylparaben, mono-butyl phthalate, mono-2-ethylhexyl phthalate, monoethyl phthalate, and monomethyl phthalate) in urine and 10 steroid hormones (dihydrotestosterone, corticosterone, hydrocortisone, 11-deoxycortisol, 17α-hydroxy progesterone, 4-androstene-3,17-dione, estrone, deoxycorticosterone, pregnenolone, and dehydroepiandrosterone) in serum were detected with the liquid chromatography-mass spectrometry (LC-MS). RESULTS: According to the Mann-Whitney U test, urinary levels of bisphenol A, monobutyl phthalate, and monomethyl phthalate were significantly higher in the precocious group than in the prepubertal group, and blood levels of hydrocortisone, 11-deoxycortisol, corticosterone, deoxycorticosterone, and pregnenolone were significantly lower in the precocious group than in the prepubertal group (p<0.05, VIP>1). CONCLUSIONS: Our findings confirm the association between phthalate exposure and the incidence of precocious puberty in girls. Control and reduction of children exposure to phthalate esters should be considered as a health priority.

Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis.

Menarche is the first occurrence of menstrual bleeding and one of the most important events of female puberty. Alarmingly, over the last several decades, the mean age at menarche (AAM) has decreased. Environmental endocrine disruptors (EEDs) are chemicals that may interfere with the endocrine system, resulting in adverse developmental, immunological, neurological, and reproductive effects in humans. Thus, the effects of EEDs on fertility and reproduction are growing concerns in modern societies. In this study, we aimed to determine the influence of genetic and environmental factors on AAM. We used data from an AAM genome-wide association study of 329,345 women to conduct a transcriptome-wide association study (TWAS) with FUSION software. As references, we determined the gene-expression levels in the hypothalamus, pituitary gland, ovaries, uterus, and whole blood. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significantly dysregulated genes identified by the TWAS. Using the STRING database, we also generated a protein-protein-interaction network to analyze common AAM-specific genes identified by the TWAS with different tissues. We performed chemical-related gene set enrichment analysis (CGSEA) and identified significant TWAS genes to uncover relationships between different chemicals and AAM. The TWAS identified 9,848 genes; among these, 1580 genes were significant (P < 0.05), and 11 genes were significant among the hypothalamus, pituitary, ovary, uterus, and whole blood. CGSEA identified 1,634 chemicals, including 120 chemicals significantly correlated with AAM. In summary, we performed a TWAS (for genetic factors) and CGSEA (for environmental factors) focusing on AAM and identified several AAM-associated genes and EEDs. The results of this study expand our understanding of genetic and environmental factors related to the onset of female puberty.

Sex-dependent and long-lasting effects of bisphenol AF exposure on emotional behaviors in mice.

We recently reported that maternal exposure to bisphenol AF (BPAF), an environmental endocrine disruptor (EED), induced significant alterations in emotional behaviors in offspring mice during adolescence in a sex-dependent manner. However, the effects of adult BPAF exposure and the potential long-lasting effects of maternal exposure to BPAF on offspring mice are still unknown. The present study aimed to investigate the neurobehavioral effects of adult and maternal exposure to BPAF, intragastrically (0.4, 4 mg•kg-1, i.g.), by using a series of classic emotional behavioral tests, mainly referring to depression, anxiety, and memory. The results showed that adult BPAF exposure significantly attenuated anxiety- and depression-like behaviors in adult male mice, while increasing anxiety-like behaviors, promoting novel object recognition memory formation, and impairing contextual fear conditioning memory formation in adult female mice. Maternal exposure to BPAF induced anxiety-like effects and anti-depression-like effects in male offspring mice during adulthood, while maternal BPAF exposure increased anxiety- and depression-like behaviors in female offspring mice during adulthood. Our present findings indicate that BPAF exposure significantly affects emotional behaviors in adult/offspring mice in a sex-dependent manner and that female adult mice are more likely to have adverse consequences to BPAF exposure during adulthood, even during early life stages.

Bisphenol S exposure induces intestinal inflammation: An integrated metabolomic and transcriptomic study.

As a typical substitute for bisphenol A (BPA), bisphenol S (BPS) is raising concerns due to the potential adverse effects on human health. Limit evidence is available to understand the toxicity of BPS to the digestive system, especially for intestine. In this study, we aimed to investigate the potential effects and underlying mechanisms of BPS exposure on human colon mucosal epithelial cells (NCM460). Our results showed that BPS exposure significantly increased the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and interleukin-17A (IL-17A). The tight junctions of the cells has been destroyed by BPS exposure, which was characterized by a down-regulation of the tight junction proteins (Claudin1 and zonula occluden 1 (ZO1)). A multi-omics study explored the underlying mechanisms based on the metabolomic and transcriptomic responses. A variety of neurotransmitters increased significantly after exposure to BPS. The top enriched pathway was "glutamatergic synapse", which was activated by BPS exposure, resulting in the up-regulation of l-glutamine. Links were observed among the altered metabolites, genes and cytokines. Our results indicate that exposure to BPS may disturb the balance of gut-brain axis, leading to the production of inflammatory cytokines and the destruction of tight junction in NCM460 cells. It provides new clue for the development of intestinal inflammation in terms of the environmental pollutants.

Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure.

The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.

Environmental exposure to bisphenol analogues and unexplained recurrent miscarriage: A case-control study.

The use of bisphenol A (BPA) has been substantially limited since 2010 due to its toxicity to human health. A group of bisphenol analogues that are structurally similar to BPA have been developed as the alternatives and used widely. The reproductive toxicity of these emerging chemicals has caused substantial concerns in recent years. Whether bisphenol analogues affect miscarriage, especially unexplained recurrent miscarriage (URM), remains to be explored. We conducted a hospital-based, case-control study with 1180 URM cases and 571 controls in China from 2014 to 2016. Concentrations of six bisphenol analogues (BPA, BPAF, BPAP, BPB, BPP and BPS) were measured in the urine samples collected at median intervals of 7.6 months after last miscarriage (interquartile ranges: 4.8, 14.7 months). Multiple logistic regression, Bayesian kernel machine regression (BKMR) and quantile g-computation (q-gcomp) were used to assess the relationship of bisphenol analogues with URM risk. We observed significantly higher levels of all urinary bisphenols in the cases than the controls. After controlling for potential confounders, bisphenol analogues were significantly associated with increased odds of URM in varying degrees. A dose-response pattern was observed for the associations of BPAF, BPAP and BPB quartiles with URM. The mixed exposure of six bisphenol analogues was positively associated with the risk of URM (adjusted odds ratio (aOR) = 1.25; 1.11-1.42), which was mainly driven by BPAP (60.1%), BPAF (25.1%) and BPA (14.8%). After age stratification, the risks tended to be higher in women aged 30 years or older, compared to women <30 years. Our large case-control study indicates that environmental exposure to bisphenol analogues is associated with an increased risk of URM. Older women may be more vulnerable to the insult.

Propylparaben concentrations in the urine of women and adverse effects on ovarian function in mice in vivo and ovarian cells in vitro.

Female reproduction is precisely regulated by hormones, and the ovary is easily affected by environmental endocrine disruptors (EDCs), which are ubiquitous in industrialized societies. Parabens are EDCs that are used as antibacterial preservatives in cosmetics, personal care products (PCPs), medicines, and food. We used ultrahigh-performance liquid chromatography-mass spectrometry to quantitatively detect methyl-, ethyl-, butyl-, and propylparaben (PP) concentrations in urine samples from 74 women of childbearing age. Balb/c mice were subcutaneously injected with 100 mg/kg/day of PP for 21 consecutive days or 100 or 1,000 mg/kg/day of PP during superovulation. Various concentrations of PP (ranging from 1 to 1,000 nM) were added to a human ovarian granulosa tumor-derived cell line (KGN) culture for 24 h. The urinary paraben concentrations of women who used cosmetics and other PCPs within 48 h prior to sample collection were significantly elevated, and the PP concentration was significantly positively correlated with the basal estradiol concentration. After PP injection, the mouse serum estradiol concentrations were significantly increased, estrus cycles were disordered, corpus luteum number was reduced, and number of oocytes retrieved was significantly reduced. In in vitro experiments, PP treatment increased estradiol synthesis and the expression levels of aromatase enzyme (CYP19A1) and steroidogenic acute regulatory protein. This study demonstrates the adverse effects of PP on ovarian estradiol secretion and ovulation, further evaluates the safety of PP as a preservative, and provides guidance for the use of PCPs and cosmetics by women of childbearing age.

Phthalate Exposure Pattern in Breast Milk within a Six-Month Postpartum Time in Southern Taiwan.

Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, has been detected in breast milk in many countries; however, whether phthalate metabolite concentration and the detection rate in breast milk change postpartum is still unknown. We measured phthalate metabolite concentrations in breast milk in the first 6 months postpartum in women enrolled in the E-Da hospital from January to July 2017. A total of 56 breastfeeding mothers and 66 samples were included in this study. We analyzed the samples' concentration of eight phthalate metabolites using liquid chromatography mass spectrometry. The concentration of mono-2-ethylhexyl phthalate (MEHP) was significantly higher in the first month, and then decreased over time. The detection rate of ono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MBP) was low in the first month and then increased over time. Compared with a previous study published in 2011, the levels of MEHP and MiBP in breast milk were much lower in the present study, suggesting an increased awareness of the health risks of phthalate exposure after a food scandal occurred in Taiwan. This study provides information for evaluating newborns' exposure to different kinds of phthalate through human milk in the postpartum period.

What is the Impact of Bisphenol A on Sperm Function and Related Signaling Pathways: A Mini-review?

Bisphenol A (BPA) is an organic synthetic compound that is ubiquitously present in daily life. It is a typical environmental endocrine disruptor that affects the functions of endogenous hormones. There is a significant negative correlation between BPA and male reproduction. This mini-review describes current research data on the negative effects of BPA on sperm functions in humans and animal models, as well as on its supposed mechanisms of action, such as CATSPER-Ca2+ signaling, cAMP-protein kinase A signaling, and epigenetic changes. The published evidence showed an adverse impact of BPA on sperm tail morphology, counts, motility, and acrosome reaction action. Sperm function related signaling pathways, such as CATSPER-Ca2+ signaling, cAMP-protein kinase A signaling, and phosphorylation signaling, as well as epigenetic changes and sperm aging, are associated with BPA exposure in human and animal models. The clear risks of BPA exposure can provide greater awareness of the potential threat of environmental contaminants on male fertility.

Maternal exposure to Di-(2-ethylhexyl) phthalate (DEHP) activates the PI3K/Akt/mTOR signaling pathway in F1 and F2 generation adult mouse testis.

Di-(2-ethylhexyl) phthalate (diethylhexyl phthalate, DEHP) can cause male reproductive damage in rodents and human. Moreover, DEHP is known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. The PI3K/Akt/mTOR signaling pathway has been implicated in germ cell survival following testicular damage. In this study, a F0 gestation DEHP exposure and transgenerational inheritance testis injury model was established to study the testis injury phenotype and the expression and activation of members of PI3K/Akt/mTOR signaling pathway in the testis of F1-F3 generation mice. We found that the bodyweight and the anogenital distance (AGD) are reduced only in F1 mice, the sperm motility and deformity decreased in F1-F3 mice, and the testicular histomorphology damagedin F1-F3 mice; however the sperm motility and deformity rates are increased and the histomorphological injury is repaired during the transgenerational process. We also found the activation of PI3K/Akt/mTOR signaling pathway is enhanced in F1 and F2, and the number of apoptotic cells is decreased in F3 generation mice compared to the control group. These results suggest that the PI3K/Akt/mTOR signaling pathway may be activated to promote the proliferation and differentiation and protect testicular cells from apoptosis in the F1 and F2 generation mice after direct exposure to DEHP.

A prominent environmental endocrine disruptor, 4-nonylphenol, promotes endometriosis development via plasmacytoid dendritic cells.

Endometriosis is an estrogen-dependent chronic inflammatory disease and is associated etiologically with environmental endocrine disruptor (EED) exposure. 4-nonylphenol (NP), a widely found EED, has weak estrogenic activity and modulates plasmacytoid dendritic cell (pDC) function in vitro and in vivo. We aimed to elucidate the immunomodulatory effect of NP on the development of endometriosis, particularly focusing on pDCs. This study established a surgically induced endometriosis murine model (C57BL/6) under conditions of NP treatment that are relevant to the level and route of human exposure. Multi-parametric flow cytometry was used for analysis of infiltrated immune cell subsets in lesions. The results showed that NP exposure significantly promoted endometriotic lesion growth, survival and angiogenesis development of lesions as well as pDC accumulation in the lesions in mice. Adoptive transfer of NP-conditioned pDCs into mice significantly enhanced lesion development and local pDC infiltration, whereas NP-conditioned conventional dendritic cells did not affect lesion growth. In vitro functional analysis showed that NP-conditioned pDCs in lesions expressed high levels of CD36, a scavenger receptor and NP-conditioned splenic pDCs secreted an enhanced level of IL-10 in response to apoptotic cell recognition in a CD36-dependent manner. Furthermore, we observed that local treatment with blocking antibodies against IL-10 and CD36 on the day of surgery significantly inhibited lesion development. NP exposure also altered the estrous cycle in mice. The results suggest that chronic and low-dose exposure to NP enhances endometriotic lesion growth by altering pDC homeostasis and function. This study has important implications for understanding the environment-innate immunity interaction in human endometriosis.

Exposure to DEHP or its metabolite MEHP promotes progesterone secretion and inhibits proliferation in mouse placenta or JEG-3 cells.

Di (2-ethyl-hexyl)phthalate (DEHP) is an environmental endocrine disruptor and commonly used as plasticizer. Maternal DEHP exposure during pregnancy reduces placental size and destroys placental structure. However, the underlying mechanisms were unclear. In this study, we supposed that DEHP disturbs endocrine function of placenta to inhibit the proliferation of placental cell. Using radioimmunoassay and ELISA, we found that DEHP and its active metabolite mono (2-ethyl-hexyl) phthalate (MEHP) promoted progesterone secretion in pregnant mouse and in JEG-3 cells, respectively. Therefore, placental endocrine function was altered by DEHP. The mRNA and protein level of progesterone synthetase 3ß-HSD1 was elevated by DEHP, which is conducive to the synthesis of progesterone. The level of progesterone receptor was down-regulated by DEHP and MEHP in mouse placenta and in JEG-3 cells, respectively. PR deficiency further promoted the level of 3ß-HSD1, which leads to a higher progesterone level. In turn, higher concentration of progesterone further inhibited the expression of PGR (PR gene). Therefore, higher progesterone down-regulated the level of its receptor PR. Meanwhile, decreased PR induced more progesterone secretion. There is a feedback loop between progesterone and PR. PR deficiency down-regulated the protein level of Cyclin D1 which plays an important role in cell proliferation. Accordingly, DEHP and its active metabolite MEHP can restrain proliferation of placental cell and disturb the progesterone secretion via decreasing the level of PR.

Ecotoxicological and biochemical effects of environmental concentrations of the plastic-bond pollutant dibutyl phthalate on Scenedesmus sp.

Phthalate esters are highly present in aquatic plastic litter, which can interfere with the biological processes in the wildlife. In this work, the commonly found freshwater microalga Scenedesmus sp. was exposed to environmental concentrations (0.02, 1 and 100 µg L-1) and to a higher concentration (500 µg L-1) of dibutyl phthalate (DBP), which is an environmental pollutant. The growth, pH variation, production of photosynthetic pigments, proteins and carbohydrates were evaluated. The main inhibition effect of DBP on the microalgal growth was observed in the first 48 h of the exposure (EC50: 41.88 µg L-1). A reduction in the photosynthetic pigment concentration was observed for the 0.02, 1 and 100 µg L-1 conditions indicating that the DBP downregulated the growth rate and affected the photosynthetic process. A significant increase in protein production was only observed under 500 µg L-1 DBP exposure. The extracellular carbohydrates production slightly decreased with the presence of DBP, with a stronger decrease occurring in the 500 µg L-1 condition. These results highlight the environmental risk evaluation and ecotoxicological effects of DBP on the production of biovaluable compounds by microalgae. The results also emphasize the importance of assessing the consequences of the environmental concentrations exposure as a result of the DBP dose-dependent correlation effects.

Effects of the Dibutyl Phthalate (DBP) on the Expression and Activity of Aromatase in Human Granulosa Cell Line KGN.

In recent years, environmental endocrine disruptors (EEDs) have received extensive attention because of their hormone-like or anti-hormone effects. Dibutyl phthalate (DBP) is not only one of the most widely-used phthalates but also a member of EEDs with the estrogenic property. Although some studies have revealed the negative effect of DBP on the reproductive system, the underlying mechanisms are still elusive. Here the effect of DBP on P450 aromatase, a rate-limiting enzyme stimulated by FSH in the estradiol synthesis, was investigated in human granulosa cell line KGN. Cultured cells were treated with FSH and various doses of DBP (0.1µM, 1µM, 10µM, 50µM, or 100µM) for 24hr. Then the expression of aromatase was assessed, and the synthesis of estradiol was detected to reflect aromatase activity. As shown by the results, all concentrations of DBP could up-regulate the mRNA as well as protein levels of aromatase, and 0.1µM DBP increased the production of estradiol significantly. Furthermore, the ovary-specific promoter of aromatase, promoter II, was activated by 0.1µM DBP, and the expression of FSH receptor (FSHR) was increased by DBP from 0.1µM to 100µM. The study results show that DBP can affect aromatase from both quantitative and functional aspects, and this process may involve the activation of aromatase promoter II and upregulation of FSHR in KGN. Additionally, low-concentration DBP, near human serum concentration, has a more robust effect. This study suggests that DBP may affect the steroidogenic capacity in human ovaries and contributes to our understanding of the effects of DBP on the female reproductive system.

Light at night as an environmental endocrine disruptor.

Environmental endocrine disruptors (EEDs) are often consequences of human activity; however, the effects of EEDs are not limited to humans. A primary focus over the past ∼30years has been on chemical EEDs, but the repercussions of non-chemical EEDs, such as artificial light at night (LAN), are of increasing interest. The sensitivity of the circadian system to light and the influence of circadian organization on overall physiology and behavior make the system a target for disruption with widespread effects. Indeed, there is increasing evidence for a role of LAN in human health, including disruption of circadian regulation and melatonin signaling, metabolic dysregulation, cancer risk, and disruption of other hormonally-driven systems. These effects are not limited to humans; domesticated animals as well as wildlife are also exposed to LAN, and at risk for disrupted circadian rhythms. Here, we review data that support the role of LAN as an endocrine disruptor in humans to be considered in treatments and lifestyle suggestions. We also present the effects of LAN in other animals, and discuss the potential for ecosystem-wide effects of artificial LAN. This can inform decisions in agricultural practices and urban lighting decisions to avoid unintended outcomes.

Promotion of proliferation of prostate in aged rats by low-dose di(2-ethylhexyl) phthalate / 中国药理学与毒理学杂志

OBJECTIVE To investigate the proliferation effect of di(2-ethylhexyl) phthalate (DEHP) on prostate in aged rats at the environmental exposure dose and the possible mechanism.METHODS Thirty-two male Sprague-Dawley rats,aged 1.5 years,were randomly divided into 4 groups (8 rats per group) and treated with DEHP (30,90 and 270 μg· kg-1,ig) and vehicle once daily respectively for 4 weeks.All the animals were anesthetized with pentobarbital sodium and sacrificed on the day subsequent to the last treatment.① Abdominal aortic blood samples were collected,and serum estradiol (E2),testosterone (T) and prolactin (PRL) levels were assayed by ELISA.② The prostate tissues were dissected and categorized into different lobes,weighed and measured.The prostate relative mass was calculated.③ The morphological changes were detected by HE staining and prostate epithelial height was analyzed with microscopic image analysis software.RESULTS Compared with vehicle control group,the prostate relative mass,dorsolateral prostate mass,and dorsolateral prostate index in DEHP 270 μg· kg-1 group were significantly higher (P＜0.05).The height of the ventral prostate epithelium in DEHP 30,90 and 270 μg· kg-1 groups was increased significantly (P＜0.01),so was the height of dorsal prostate epithelium in DEHP 270 μg· kg-1 group (P＜0.01).There were no significant changes in levels of E2,PRL or T in DEHP 30,90 and 270 μg· kg-1 groups,but the ratios of E2/T in DEHP 30 and 270 μμg· kg-1 groups were increased significantly (P＜0.05).CONCLUSION Low-dose DEHP could promote the proliferation of prostatic hyperplasia in the aged rats,which might be associated with the relative levels of endogenous hormone.

Supplemental dietary phytosterin protects against 4-nitrophenol-induced oxidative stress and apoptosis in rat testes.

4-Nitrophenol (PNP), is generally regarded as an environmental endocrine disruptor (EED). Phytosterin (PS), a new feed additive, possesses highly efficient antioxidant activities. The transcription factor, nuclear factor-erythroid 2-related factor 2 (Nrf2), is an important regulator of cellular oxidative stress. Using rats, this study examined PNP-induced testicular oxidative damage and PS-mediated protection against that damage. The generation of MDA and H2O2 upon PNP and PS treatment was milder than that upon treatment with PNP alone. This mitigation was accompanied by partially reversed changes in SOD, CAT, GSH and GSH-Px. Moreover, PNP significantly reduced the caudal epididymal sperm counts and serum testosterone levels. Typical morphological changes were also observed in the testes of PNP-treated animals. PNP reduced the transcriptional level of Nrf2, as evaluated by RT-PCR, but it promoted the dissociation from the Nrf2 complex, stabilization and translocation into the nucleus, as evaluated by immunohistochemistry and Western blotting. In addition, PNP enhanced the Nrf2-dependent gene expression of heme oxygenase-1 (HO-1) and glutamate-cysteine ligase catalytic subunit (GCLC). These results suggest that the Nrf2 pathway plays an important role in PNP-induced oxidative damage and that PS possesses modulatory effects on PNP-induced oxidative damage in rat testes.