Xenoestrogens Research Articles

Diethylstilbestrol exposure disrupts mouse oocyte meiotic maturation in vitro through affecting spindle assembly and chromosome alignment

An adverse tendency induced by the environmental estrogens in female reproductive health is one serious problem worldwide. Diethylstilbestrol (DES), as a synthetic estrogen, is still used as an animal growth stimulant in terrestrial livestock and aquaculture illegally. It has been reported to negatively affect ovarian function and oogenesis. Nevertheless, the mechanism and toxicity of DES on oocyte meiotic maturation are largely unknown. Herein, we found that DES (40 μM) intervened in mouse oocyte maturation and first polar body extrusion (PBE) was decreased in vitro. Cell cycle analysis showed meiotic process was disturbed with oocytes arrested at metaphase I (MI) stage after DES exposure. Further study showed that DES exposure disrupted the spindle assembly and chromosome alignment, which then continuously provoke the spindle assemble checkpoint (SAC). We also observed that the acetylation levels of α-tubulin were dramatically increased in DES-treated oocytes. In addition, the dynamics of actin were also affected. Moreover, the distribution patterns of estrogen receptor α (ERα) were altered in DES-treated oocyte, as indicated by the significant signals accumulation in the spindle area. However, ERα inhibitor failed to rescue the defects of oocyte maturation caused by DES. Of note, the same phenomenon was observed in estrogen-treated oocytes. Collectively, we showed that DES exposure lead to the oocyte meiotic failure via impairing the spindle assembly and chromosome alignment. Our research is helpful to understand how environmental estrogen affects female germ cells and contribute to design the potential therapies to preserve fertility especially for occupational exposure.

Environmental estrogens and progestins disturb testis and brood pouch development with modifying transcriptomes in male-pregnancy lined seahorse Hippocampus erectus.

Exposure to environmental estrogens and progestins has contributed to adverse effects on the reproduction of many aquatic wildlife species. However, few reports have paid attention to fish species with specialized reproductive strategies, such as male-pregnancy seahorses. In this study, the potential effects on the behavior, gonad and brood pouch development, and transcriptomic profiles of lined seahorse Hippocampus erectus exposed to environmentally relevant concentrations of 17α-ethynyl estradiol (EE2, 5ng/L, 50ng/L, 10ng/L, 100ng/L) or progesterone (P4) for 60days were examined. Both EE2 and P4 significantly inhibited male brood pouch development by disrupting the extracellular matrix and basement membrane pathways. In addition, both EE2 and P4 impaired the expression of genes associated with spermatogenesis in the testis, and even caused male feminization. We suggest that seahorses be regarded as a sensitive indicator for evaluating the potential effects of endocrine disrupting chemical (EDC) pollution on aquatic biotic communities.

Oxidative stress, ion concentration change and immune response in gills of common carp (Cyprinus carpio) under long-term exposure to bisphenol A

Bisphenol A (BPA) is a well-known phenolic environmental estrogen, widely distributed in the aquatic environment, which poses a toxic risk to the health of aquatic organisms. This study aimed to assess the effect of BPA on common carp gills by analyzing oxidative stress, ion equilibrium and immune response. Fish were exposed to five concentrations of BPA (0, 0.01, 0.1, 0.5, and 2 mg/L) for 30 days. Then gills were collected to assay biochemical parameters and gene expression. The results showed that BPA could decrease the levels of total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH) and glutathione S-transferase (GST) and increase the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and 8-hydroxy-2 deoxyguanosine (8-OHdG). The gene expression showed that BPA (2 mg/L) could affect the nuclear erythroid 2-related factor 2 (nrf2) signaling pathway, upregulate the gene expression of nrf2 and heme oxygenase 1 (ho-1). Meanwhile, BPA was found to change the activity of Na+/K+ ATPase, and increased the concentrations of Na+ and Ca2+ in gills of common carp. Also, high BPA concentration (0.5 or 2 mg/L) exposure increased the activity of alkaline phosphatase (AKP), blocked mRNA level of lysozyme-c (c-lyz), activated Toll-like receptors (TLRs) signaling pathway, enhanced the mRNA levels of toll-like receptor 2 (tlr2), receptor 4 (tlr4), myeloid differentiation factor 88 (myd88), interferon regulatory factor 3 (irf3), interleukin 1β (il-1β), interleukin 6 (il-6) and interleukin 10 (il-10). Overall, these results suggested that high BPA could induce oxidative damage, ion imbalance, immunosuppression and inflammatory response in gills of common carp.

Missing Information from the Estrogen Receptor Puzzle: Where Are They Localized in Bull Reproductive Tissues and Spermatozoa?

Estrogens are steroid hormones that affect a wide range of physiological functions. The effect of estrogens on male reproductive tissues and sperm cells through specific receptors is essential for sperm development, maturation, and function. Although estrogen receptors (ERs) have been studied in several mammalian species, including humans, they have not yet been described in bull spermatozoa and reproductive tissues. In this study, we analyzed the presence of all types of ERs (ESR1, ESR2, and GPER1) in bull testicular and epididymal tissues and epididymal and ejaculated spermatozoa, and we characterize them here for the first time. We observed different localizations of each type of ER in the sperm head by immunofluorescent microscopy. Additionally, using a selected polyclonal antibody, we found that each type of ER in bull sperm extracts had two isoforms with different molecular masses. The detailed detection of ERs is a prerequisite not only for understanding the effect of estrogen on all reproductive events but also for further studying the negative effect of environmental estrogens (endocrine disruptors) on processes that lead to fertilization.

Abnormal differentiation of regulatory T cells and Th17 cells induced by perinatal bisphenol A exposure in female offspring mice

Bisphenol A (BPA) is an environmental estrogen widely exposed to human beings, and there are more studies on its reproductive toxicity, endocrine disruption and neurobehavioral disorders. Recent few studies have found that BPA has immunotoxicity, and its mechanism is not clear. Therefore, the effects of BPA on immune system have attracted extensive attention. The aim of this study was to investigate the effect and mechanism of perinatal exposure to BPA on regulatory T cells (Treg) and Th17 cells in female offspring mice. Twenty-one pregnant C57BL/6 mice were randomly divided into three groups: a control group, low-dose BPA (0.2 µg/mL) and high-dose BPA (2.0 µg/mL) exposure group. All received BPA exposure via drinking water from gestational day 6 to the end of lactation. Female offspring were fed a normal diet and drinking water for 1 month. The percentages of Treg and Th17 cells, the levels of Foxp3 and RORγt protein and IL-17 and TGF-β from spleen tissue or blood were measured in female offspring. The percentage of Treg cells and levels of Foxp3 protein decreased, while the percentage of Th17 cells and levels of RORγt protein increased, which showed a dose–effect relationship. The levels of serum TGF-β were significantly lower and the levels of serum IL-17 were statistically higher in BPA-exposed female offspring compared with controls (P 0.05). BPA exposure during pregnancy and lactation could cause abnormal differentiation and function of Treg and Th17 cells in female offspring mice, which was associated with down-regulated Foxp3 and up-regulated RORγt protein, respectively. Our findings indicated that BPA exposure during early development may play an important role in the development of autoimmune diseases later.

Temperature and Estrogen Alter Predator-Prey Interactions between Fish Species.

SynopsisA variety of environmental estrogens are commonly detected in human-impacted waterways. Although much is known about the effects of these environmental estrogens on the reproductive physiology and behavior of individuals within species, comparatively less is known about how these compounds alter the outcomes of interactions between species. Furthermore, few studies have considered how the effects of contaminants are modulated by natural variation in abiotic factors, such as temperature. To help fill this knowledge gap, we conducted a factorial experiment to examine the independent and combined effects of estrone (E1) and temperature on the outcome of predator–prey interactions between two common North American freshwater fishes, fathead minnows (Pimephales promelas) and bluegill sunfish (Lepomis macrochirus). Larval fathead minnows and adult sunfish were exposed to either a low (mean±standard deviation, 90.1 ± 18 ng/L; n = 16) or high (414 ± 147 ng/L; n = 15) concentration of E1 or to a solvent control for 30 days at one of four natural seasonal temperatures (15°C, 18°C, 21°C, and 24°C) before predation trials were performed. Exposure to E1 was associated with a significant increase in larval predation mortality that was independent of temperature. Across all temperature treatments, approximately 74% of control minnows survived; this survivorship significantly exceeded that of minnows exposed to either concentration of E1 (49% and 53% for minnows exposed to the low and high concentrations, respectively). However, exposure to E1 also impaired the prey-capture success of sunfish, partially mitigating predation pressure on exposed minnows. Overall prey-capture success by sunfish showed an inverted U-shaped distribution with temperature, with maximal prey consumption occurring at 21°C. This study illustrates the vulnerability of organismal interactions to estrogenic pollutants and highlights the need to include food web interactions in assessments of risk.

Environmental estrogen exposure disrupts sensory processing and nociceptive plasticity in the cephalopod Euprymna scolopes.

Endogenous estrogens affect multiple sensory systems, including those involved in processing noxious and painful stimuli. Extensive evidence demonstrates that estrogenic environmental pollutants have profound, negative effects on growth and reproductive physiology, but there is limited information about how estrogenic pollutants might affect sensory systems known to be modulated by endogenous estrogens. Here, we show that ethinyl estradiol, the most common artificial estrogen found in coastal marine environments, disrupts normal behavioral and neural responses to tissue injury in the sepiolid Euprymna scolopes (Hawaiian bobtail squid), which inhabits shallow tropical waters close to dense human habitation. Behavioral hypersensitivity and neural plasticity that occur normally after tissue injury were impaired both under chronic estrogen exposure beginning during embryogenesis and after a single, high dose co-incident with injury. This suggests that these naturally selected responses to injury, which function to protect animals from predation and infection risk, may be impaired by anthropogenic pollution.

Recent Progress of SERS for Environmental Estrogen Detection

Recent Progress of SERS for Environmental Estrogen Detection

Identification of non-accumulating intermediate compounds during estrone (E1) metabolism by a newly isolated microbial strain BH2-1 from mangrove sediments of the South China Sea.

Steroid estrogens are natural hormonal compounds produced by various animals and humans. Estrone (E1), estradiol (E2), and estriol (E3) are the most commonly known estrogens that are released into the environment along with human and animal excreta, which end up polluting water bodies. While these estrogens are usually biotransformed into their respective by-products by various microbial strains, E2 could also be transformed into E1 by 17β-hydroxysteroid dehydrogenases (17β-HSDs) under reducing environmental conditions. However, due to limited further biotransformation of E1, it accumulates to higher levels in water bodies compared to other natural estrogens in the aquatic environment. Given that E1 is one of the potential endocrine-disrupting compounds (EDCs), with several adverse effects on aquatic animals and consequently on the seafood industry, it is vital to remove E1 from the environment via improved steroid bioremediation. In the present study, we successfully isolated a potential E1-degrading microbial strain (named as BH2-1) from soil sediments collected from the Bai Hai mangrove region of the South China Sea. The strain BH2-1 has excellent E1-degrading potential and could degrade 89.5% of E1 after 6days of incubation in a MSM-E1 medium containing 1% NaCl at pH6. Besides, after 3h and 6h of extraction, two non-accumulating intermediate compounds [3-hydroxyandrosta-5,7,9(11)-trien-17-one and androsta-1,4,6-triene-3,17-dione (ATD)], respectively, were successfully identified using GC-MS analysis. These non-accumulating intermediate compounds have not previously been reported during E1 biodegradation and might be new intermediate metabolites. The identification of these new compounds also gives more insight into the mechanism of E1 metabolism and helps to establish a clear E1 biodegradation pathway, which further enriches our knowledge on the overall microbial steroid degradation pathway. Furthermore, whole-genome sequence analysis of strain BH2-1 revealed the presence of 46 genes that belong to 6 major steroid-degrading gene classes.

Characterization of an 17β-estradiol-degrading bacterium Stenotrophomonas maltophilia SJTL3 tolerant to adverse environmental factors.

Bioremediation of environmental estrogens requires microorganisms with stable degradation efficiency and great stress tolerance in complex environments. In this work, Stenotrophomonas maltophilia SJTL3 isolated from wastewater was found to be able to degrade over 90% of 10μg/mL 17β-estradiol (E2) in a week and the degradation dynamic was fitted by the first-order kinetic equations. Estrone was the first and major intermediate of E2 biodegradation. Strain SJTL3 exhibited strong tolerance to several adverse conditions like extreme pH (3.0-11.0), high osmolality (2%), co-existing heavy metals (6.25μg/mL of Cu2+) and surfactants (5 CMC of Tween 80), and retained normal cell vitality and stable E2-degradaing efficiency. In solid soil, strain SJTL3 could remove nearly 100% of 1μg/mL of E2 after the bacteria inoculation and 8-day culture. As to the contamination of 10μg/mL E2 in soil, the biodegradation efficiency was about 90%. The further obtainment of the whole genome of strain SJTL3 and genome analysis revealed that this strain contained not only the potential genes responsible for estrogen degradation, but also the genes encoding proteins involved in stress tolerance. This work could promote the estrogen-biodegrading mechanism study and provide insights into the bioremediation application.

Physiological and Transcriptional Effects of Mixtures of Environmental Estrogens, Androgens, Progestins, and Glucocorticoids in Zebrafish

Fishes are exposed to mixtures of different classes of steroids, but ecotoxicological implications are not sufficiently known. Here, we systematically analyze effects of different combinations of steroid mixtures in zebrafish embryos to assess their joint activities on physiology and transcriptional alterations of steroid-specific target genes at 96 and 120 h post fertilization. In binary mixtures of clobetasol propionate (CLO) with estradiol (E2) or androstenedione (A4), each steroid exhibited its own expression profile. This was also the case in mixtures of 5-, 8-, and 13-different classes of steroids in exposure concentrations of 10-10,000 ng/L. The transcriptional expression of most genes in different mixtures was steroid-specific except for genes encoding aromatase (cyp19b), sulfotransferase (sult2st3), and cyp2k22 that were induced by androgens, progestins, and glucocorticoids. Marked alterations occurred for sult2st3 in binary mixtures of CLO + E2 and CLO + A4. Glucocorticoids increased the heart rate and muscle contractions. In mixtures containing estrogens, induction of the cyp19b transcript occurred at 10 ng/L and protc from the anticoagulation system at 100 ng/L. Our study demonstrates that steroids can act independently in mixtures; the sum of individual steroid profiles is expressed. However, some genes, including cyp19b, sult2st3, and cyp2k22, are regulated by several steroids. This joint effect on different pathways may be of concern for fish development.

Field survey of environmental estrogen pollution in the coastal area of Tokyo Bay and Nagasaki City using the Japanese common goby Acanthogobius flavimanus

Endocrine disrupting chemicals (EDCs) are common pollutants in coastal waters. To investigate the estrogen risk of EDCs in the coastal areas of Japan, the Japanese common goby, which is a commonly observed species in these waters, was used as the target fish. Plasma 17β-estradiol (E2) and vitellogenin (VTG) levels were analyzed and the gonads of fish collected from the Taira River (northern Nagasaki, reference site), Nagasaki Port, and two sites in Tokyo Bay were observed. Abnormal levels (>150 ng/mL, p < 0.05) of plasma VTG and high levels of plasma E2 were detected in the fish from Nagasaki Port and Tokyo Bay, whereas the levels of both were low in the fish from the Taira River. The target EDCs, including natural estrogen [estrone (E1), and E2] and alkylphenols [4-t-octylphenol (4-t-OP), 4-nonylphenol (4-NP), and bisphenol-A (BPA)] in water samples were quantified using gas chromatography tandem mass spectrometry (GC/MS/MS), respectively. It was observed that the E2-equivalent (EEQ) in Nagasaki Port and Tokyo Bay, which was calculated from the actual EDC measurement value, were almost 20- and 150-fold higher, respectively, than that at the reference site (Taira River, 0.021 ng/L). The EEQs mostly comprised natural estrogen in the sampling sites, although there was some influence of alkylphenols. There was an association between the EEQ and the E2 in environmental water, suggesting a high estrogen risk in Japan coastal waters. Moreover, the results indicated that abnormal VTG synthesis was induced by environmental estrogen (EE) pollution in Nagasaki Port and Tokyo Bay.

The steroid receptor coactivator 1 (SRC1) and 3 (SRC3) recruitment as a novel molecular initiating event of 4-n-nonylphenol in estrogen receptor α-mediated pathways.

Recently, the action of steroid receptor coactivators (SRCs) has been recognized to be an important molecular initiating event (MIE) in estrogenic adverse outcome pathways (AOPs). However, the role of SRCs in the molecular mechanisms of many highly concerned environmental estrogens remains poorly understood. In this study, the widely studied environmental estrogen, 4-n-nonylphenol (4-n-NP), was used as a typical pollutant to study SRCs recruitment in its estrogenic effects. In MCF7 cell proliferation (E-SCREEN) assay and MVLN cell assay, 4-n-NP showed significant estrogenic potency that involved an increase in estrogen receptor α (ERα), SRC1 and SRC3 transcript levels. Moreover, 4-n-NP was found to induce estrogen response element (ERE)-mediated activity via ERα in MVLN cells. To investigate the mechanism by which SRCs recruitment is induced by 4-n-NP-ERα, a coactivators recruitment assay was performed, and the results showed that 4-n-NP-ERα recruited both SRC1 and SRC3, whereas it failed to recruit SRC2. Similarly, it had no interaction with SRC2 in the ERα-SRC2 two-hybrid yeast assay. This is the first report to investigate the novel MIE of SRCs recruitment in 4-n-NP-ERα-induced estrogenicity. Overall, our results suggest that the action of 4-n-NP on estrogenic effects involves the following MIEs: the activation of ERα, the recruitment of SRC1 and SRC3, and the induction of ERE-mediated activity. The findings also provide valuable insights into the MIE associated with the different SRCs that are recruited in the adverse outcome pathways of environmental estrogens.

Mo-doped porous BiVO4/Bi2S3 nanoarray to enhance photoelectrochemical efficiency for quantitative detection of 17β-estradiol

A new porous nanoarray is constructed as sensing platform of photoelectrochemical (PEC) biosensor for detection of 17β-estradiol (E2) by using aptamer. The molybdenum (Mo) ions doped into porous bismuth vanadate (Mo-p BiVO4) nanoarray by electrodeposition of BiOI nanoarray. Then, the bismuth sulfide (Bi2S3) nanoparticles are grown in-situ on the surface of Mo-p BiVO4 by the self-sacrificial synthesis method to form novel Mo-p BiVO4/Bi2S3 heterojunction. Herein, the Mo-p BiVO4/Bi2S3 heterojunction presents a high PEC signal because of Mo-p BiVO4 could increase electron-hole separation yield by supplying additional free electrons, furthermore the heterojunction of Mo-p BiVO4/Bi2S3 could promote ultrafast transfer of charge and inhibit the recombination of e−/h+ pairs by presenting cascade band-edge levels under irradiation of the visible light. Moreover, the nanoarray structure has large specific surface area, which could accelerate electron transfer and provide large number of binding sites to immobilize aptamer. This PEC aptamer sensor exhibits high sensitivity with a detection limit 3.2 × 10-4 pM and a good photocurrent response toward target E2 in the range of 1 × 10-3 - 5 × 102 pM. Good specificity and stability are acquired for analysis of E2 in human urine. Importantly, this designed sensor platform of Mo-p BiVO4/Bi2S3 heterojunction provides a new promising application for other environmental estrogen analysis.

Abstract DP-015: BIOTINYLATED ESTROGENS A NOVEL TOOL FOR EARLY DETECTION OF ADDUCT IN OVARIAN CANCER

Abstract Elevated estrogens exert their carcinogenic effects by at least three different mechanisms; they promote cell proliferation by transcriptional regulation of estrogen responsive genes, cause generation of reactive oxygen species and other free radicals, and directly react with DNA and form potentially mutagenic adducts. However, unbalanced estrogen metabolism has been linked to development of several malignant diseases including breast, endometrial and ovarian cancer and has been identified as a risk factor for these cancers. The metabolic breakdown of estogens is regulated by a series of reactions mediated by hepatic and peripheral enzymes that balances the induction and reduction of cellular stress. An imbalance in this enzymes and processes can lead to highly reactive catechol estrogen metabolites that can react with DNA, form carcinogenic DAN-adducts and lesions. Although several studies established a connection between estrogen-induced DNA damage and carcinogenesis, the underlying molecular mechanisms have been difficult to study because of the technical challenges in detecting and analyzing the variety of different DNA lesions that are formed by estrogen compounds. Moreover, detection and analysis of these adducts are important to directly monitor estrogen metabolites induced cellular responses in the cells. Towards this, we developed a novel method using biotinylated-estrogens that allows immunodetection of estrogen-induced DNA adducts by Slot-blot and single-cell molecular combing and proximity ligation assays. Using these modified estrogens we first time quantitatively detected these adducts on DNA by immune Slot-blot techniques and on DNA fibers. Furthermore, similar to other environmental carcinogens estrogens activates replication associated DNA damage responses and induces chromosomal instability. Hence, first time our studies demonstrate that biotin-labeled estrogens could be a powerful tool to detect estrogen adducts and to probe associated DNA damage responses and cellular responses. Citation Format: Kaushlendra Tripathi, Chinnadurai Mani, David W. Clark, Komaraiah Palle. BIOTINYLATED ESTROGENS A NOVEL TOOL FOR EARLY DETECTION OF ADDUCT IN OVARIAN CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-015.

Effect of Both Bisphenol - A and Liquorice on Some Sexual Hormones in Male Albino Rats and Illustration of the Effect of Stem Cell Enhancer on Their Actions

Background: Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, bisphenol A (BPA) and phthalates. "Dietary estrogen" is also called phytoestrogen, which is a plantderived xenoestrogen not generated within the endocrine system, but consumed by eating phytoestrogenic plants. Stem cell enhancer (SCE) (StemEnhance®) is a novel mobilizer of bone marrow adult stem cells that was shown to increase the number of circulating stem cells. Objectives: The aim of the current work was to clarify the effect of both BPA and liquorice together on some sexual hormones and illustration of the effect of stem cell enhancer on their actions. Materials and methods: Thirty male albino rats were used and were divided into three groups: Group I: control (untreated group), group II: rats treated with BPA and liquorice and group III: rats treated with BPA and anise oil in addition to stem cell enhancer. Blood samples were collected for different biochemical investigations. Results: There was a highly significant increase (p < 0.01) in the level of ALT and AST activities, urea, creatinine, FSH, prolactin, total cholesterol, triglycerides, LDL-C, VLDL, LDL/HDL and TC/HDL. While, there was highly significant decrease (p < 0.01) in HDL-C, total protein, albumin, globulin, testosterone and LH. These results turned back to the normal values after receiving the SCE as compared to normal group. Conclusion: It could be concluded that phytoestrogen and xenoeostrogen have undesirable effects and it is recommended to minimize the utilization of these compounds to protect people from its hazardous effects.

Effect of Both Bisphenol - A and Liquorice on Some Sexual Hormones in Male Albino Rats and Illustration of the Effect of Stem Cell Enhancer on Their Actions

Background: Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, bisphenol A (BPA) and phthalates. Dietary estrogen is also called phytoestrogen, which is a plantderived xenoestrogen not generated within the endocrine system, but consumed by eating phytoestrogenic plants. Stem cell enhancer (SCE) (StemEnhance®) is a novel mobilizer of bone marrow adult stem cells that was shown to increase the number of circulating stem cells. Objectives: The aim of the current work was to clarify the effect of both BPA and liquorice together on some sexual hormones and illustration of the effect of stem cell enhancer on their actions. Materials and methods: Thirty male albino rats were used and were divided into three groups: Group I: control (untreated group), group II: rats treated with BPA and liquorice and group III: rats treated with BPA and anise oil in addition to stem cell enhancer. Blood samples were collected for different biochemical investigations. Results: There was a highly significant increase (p < 0.01) in the level of ALT and AST activities, urea, creatinine, FSH, prolactin, total cholesterol, triglycerides, LDL-C, VLDL, LDL/HDL and TC/HDL. While, there was highly significant decrease (p < 0.01) in HDL-C, total protein, albumin, globulin, testosterone and LH. These results turned back to the normal values after receiving the SCE as compared to normal group. Conclusion: It could be concluded that phytoestrogen and xenoeostrogen have undesirable effects and it is recommended to minimize the utilization of these compounds to protect people from its hazardous effects.

Distribution of vitellogenin in Japanese flounder (Paralichthys olivaceus) for biomarker analysis of marine environmental estrogens

Estrogen pollution in marine environments has become a research hotspot due to its adverse effects on the reproduction of wild organisms. To early detection of estrogen pollution, this study developed two methods for detecting Japanese flounder vitellogenin (Vtg), a sensitive biomarker for environmental estrogens. Firstly, monoclonal antibodies (mAb) specific to Vtg were prepared using purified lipovitellin (Lv), a main Vtg-derived yolk protein. Anti-Lv mAb (C1F1) had the highest titer (1:256,000) and was labeled with fluorescein isothiocyanate to establish a direct immunofluorescence (DIF) method for histological detection of Vtg in tissues. Additionally, using the purified Lv and mAb, an enzyme-linked immunosorbent assay (ELISA) was developed and this assay had a detection limit of 0.75 ng/mL and a working range of 1.95–250 ng/mL. Furthermore, Vtg induction in the plasma of Japanese flounder exposed to 17β-estradiol (E2), 17α-ethinylestradiol (EE2), and bisphenol A (BPA) were quantified by ELISA, and Vtg induction in the liver of EE2-exposed Japanese flounder were measured by DIF. Finally, the distribution of Vtg in Japanese flounder was detected using these two methods. The results revealed that Vtg mainly appeared in the terminal tail fin, liver, kidney, intestine, and spleen. Considering the high concentration of Vtg and easy sample collection, the terminal tail fin could be a new alternative to plasma for Vtg quantification, while kidney and liver are suitable for histological detection of Vtg.

The impact of metalloestrogens on the physiology of male reproductive health as a current problem of the XXI century.

In the XXIst century in highly developed countries, progressively decreasing male reproductive potential is indicated. In recent years epidemiological studies indicate the deterioration of semen parameters: reduction of ejaculate volume, sperm count, and mobility, as well as abnormalities in their morphology. Male infertility can result from many different agents, such as: anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies and lifestyle (especially obesity, heat and tobacco smoking). It is well documented that adverse changes in male fertility also seem to be associated with environmental exposure to different substances, especially endocrine active factors, known as xenoestrogens, and among these metal ions, known as metalloestrogens, are very important. The role of some metalloestrogens in various diseases, both in women and men, is known and particularly well-proven in women, but still little is known about their role in the regulation of male reproductive potential. Thus we decided to analyse the available information exploring this problem. The review was carried out using the Medline and Google Scholar databases, using the keywords: xenoestrogens, metalloestrogens, male fertility, semen quality, male reproductive potential, mechanisms of metalloestrogen action, environmental pollution and the name of the particular metal. Articles published between 2000 - 2019 have been taken into account, including human and vertebrate animal studies and cell lines. The aim of this review is to discuss the role and mechanisms of action of fifteen metalloestrogens in the human organism, as well as in animal models, and cell cultures, paying special attention to their influence on the physiology of male reproductive health, according to the current state of knowledge. The role of certain metals in human reproduction is still poorly investigated and for some of them only single studies are available. Many factors in our daily lives have a significant impact on male fertility, therefore education is necessary on the threats and how they may be eliminated as far as possible.

Environmentally Relevant Concentrations of Bisphenol A Interact with Doxorubicin Transcriptional Effects in Human Cell Lines.

The worldwide production of synthetic chemicals, including endocrine disruptor chemicals (EDCs), such as Bisphenol A (BPA) has increased significantly in the last two decades. Human exposure to BPA, particularly through ingestion, is continuous and ubiquitous. Although, considered a weak environmental estrogen, BPA can induce divergent biological responses through several signaling pathways, including carcinogenesis in hormone-responsive organs. However, and despite the continuous increase of tumor cell-resistance to therapeutic drugs, such as doxorubicin (DOX), information regarding BPA drug interactions is still scarce, although its potential role in chemo-resistance has been suggested. This study aims to assess the potential interactions between environmentally relevant levels of BPA and DOX at a therapeutic dosage on Hep-2 and MRC-5 cell lines transciptome. Transcriptional effects in key-player genes for cancer biology, namely c-fos, p21, and bcl-xl, were evaluated through qRT-PCR. The cellular response was analyzed after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis showed that BPA exposure induces upregulation of bcl-xl and endorses an antagonistic non-monotonic response on DOX transcriptional effects. Moreover, the BPA interaction with DOX on c-fos and p21 expression emphasize its cellular specificity and divergent effects. Overall, Hep-2 was more susceptible to BPA effects in a dose-dependent manner while MRC-5 transcriptional levels endorsed a non-monotonic response. Our data indicate that BPA environmental exposure may influence chemotherapy outcomes, which emphasize the urgency for a better understanding of BPA interactions with chemotherapeutic agents, in the context of risk assessment.