Xenoestrogens challenge 17β-estradiol protective effects in colon cancer

Several epidemiological,cellular,and molecular studies demonstrate the role of environmental chemicals with endocrine disrupting activities,typical of Westernized societies,in the pathogenesis of numerous diseases including cancer.Nonetheless this information,the design and execution of studies on endocrine disruptors are not yet cognizant that the specific actions of individual hormones often change with development and ageing,they may be different in males and females and may be mediated by different receptors isoforms expressed in different tissues or at different life stages.These statements are particularly true when assessing the hazard of endocrine disruptors against 17β-estradiol(E2)actions in that this hormone is crucial determinant of sexrelated differences in anatomical,physiological,and behavioral traits which characterize male and female physiology.Moreover,E2 is also involved in carcinogenesis.The oncogenic effects of E2 have been investigated extensively in breast and ovarian cancers where hormone-receptor modulators are now an integral part of targeted treatment.Little is known about the E2preventive signalling in colorectal cancer,although this disease is more common in men than women,the difference being more striking amongst pre-menopausal women and age-matched men.This review aims to dissect the role and action mechanisms of E2 in colorectal cancer evaluating the ability of estrogen disruptors(i.e.,xenoestrogens)in impair these E2 actions.Data discussed here lead to define the possible role of xenoestrogens in the impairment and/or activation of E2signals important for colorectal cancer prevention.

Impact of xenoestrogens on sex differentiation and reproduction in teleosts

Among vertebrates,teleosts display a wide array of sex determination and differentiation mechanisms ranging from chromosomal sex determination on one end of the spectrum to environmental sex determination on the other end.However,the interplay of both these mechanisms is also not uncommon.Several gonochoristic fishes exhibit gonadal plasticity often resulting in sex reversal.The major manipulation of sex differentiation in teleost is affected by sex steroids.In this context,the increasing contamination of aquatic ecosystems by estrogen-like compounds,commonly known as xenoestrogens,is of major concern.This often leads to deleterious effects on the reproductive success of fish and thereby adversely impacts aquatic biodiversity.In the present review,we have focused on impact of xenoestrogen at different levels of the reproductive system influencing not only gonadal differentiation in teleosts but also their reproductive functions.The review would also explore the mitigation strategies and regulations in place for aquatic xenoestrogen management.

Xenoesterogens and male infertility:myth or reality?

Aim: To evaluate the role of polychlorinated biphenyls (PCBs) as a potential environmental hazard in the deteriora-tion of male fertility. Methods: Fifty-three males were studied. After a thorough case history evaluation and rele-vant clinical and laboratory investigations, PCBs were estimated in the seminal plasma of 21 infertile men with 'Unex-plained Male Factor' and 32 fertile controls. Peak retention times of the eluants were compared with those of the com-mercially available standard PCB Mix, and the results confirmed spectrophotometrically. Seminal PCB concentrafonswere compared between i) fertile and infertile men and ii) men from different areas and diets. The relationship betweenPCB concentrations and measures of sperm quality such as the total motile sperm count, was assessed. Results:PCBs were detected in seminal plasma of infertile men but absent from controls. Sperm quantity and quality were sig-nificantly lower in infertile men compared to controls. The highest average PCB concentrations were found in fish-eat-ing urban dwellers, and followed in succession by fish-eating rural dwellers, non fish-eating urban dwellers and nonfish-eating mral dwellers. The total motile sperm counts were inversely proportional to the PCB concentrations and weresignificantly lower than those of the respective controls. Conclusion: PCBs may be instrumental in the deteriorationof sperm quantity and quality, a contaminated fish diet being the main source of exposure.(Asian J Androl 2000 Dec; 2: 263-269 )

Induction of testis-ova in nile tilapia (Oreochromis niloticus) exposed to 17β-estradiol

The efficacy of Endocrine Disrupting Compounds (EDCs), 17β-estradiol was tested on the fish Oreochromis niloticus in order to understand the intersex relationship of fish, in which sequential hermaphrodism can consist of a male changing into a female (protandry) or a female changing into a male (protogyny). The fish were equally divided into 3 groups. The first group was the control group;the second and third groups were treated with 10 and 100 mg L-1 of 17β-estradiol, respectively, for 30 days. The overall result in this experiment had no significant effect on the growth parameters. Among the two treated groups, the low concentration group shows results similar to those of the control groups. The high concentration group shows changes to the male reproductive system with the appearance of the testis-ova present resulting in an intersex condition of the male gonads. With this experiment, it can be concluded that 17β-estradiol at high concentration reveals positive changes towards the male reproductive system of the fish, Oreochromis niloticus.

Alleviation of Drought Stress in Arabidopsis thaliana by 17β-Estradiol Application

Animal steroidal hormones, including estrogens, are being introduced into the agricultural soil and water supply from increased pharmaceutical and farm waste. Considering the current levels of xenoestrogen contamination of plant environments in view of the climate change induced drought conditions, this study was designed to understand the effect of estradiol (ES) application on Arabidopsis drought stress responses. Estradiol treatment (10 nM, 100 nM) of plants subjected to drought stress conditions by withholding water for 7 days resulted in increased tolerance to drought stress reflected in the significantly higher plant survival rates of 74% and 78%, respectively compared to control plants’ survival rates of 36% (no treatment) and 40% (mock treatment). Estradiol application significantly increased the content of glutathione, proline and H2O2 and significantly enhanced the transcription of the stress responsive genes GSTU3, GER5, HSP101, and HSP70b. A high concentration of ES (10 μM) did not protect plants against drought stress and proved to be toxic. These results provide new insight into the effect of ES on drought-stress responses in Arabidopsis with possible practical agricultural applications regarding the effect of environmental estrogens on crop plants.

Impact of inorganic and organic pollutants from a Belgian wastewater treatment plant on adjacent surface and groundwaters

Under the pressure of global droughts and water shortage,it is essential to evolve toward a sustainable and robust water system.One possible avenue is the maximum reuse of treated wastewater,but the quality of which determines its reuse.Therefore,inorganic(Cd,Pb,Cr,Ni,Cu,and As)and organic(xenoestrogens and polycyclic aromatic contaminants,PACs)contaminants were monthly monitored in an effluent of the wastewater treatment plant(WWTP),the surrounding surface waters and the local groundwater in Belgium.Dissolved and particulate concentrations of inorganic contaminants in these water bodies were analyzed.In addition,Diffusive Gradients in Thin-films(DGT)was used in situ to obtain bioavailable metal fractions.In the WWTP effluent and surface waters,only Ni exceeds the Annual Average-Environmental Quality Standard(AA-EQS),while in the groundwater,dissolved As was the predominant element.Moreover,in the surface and effluent waters the highest lability degrees were observed for Cd and Ni.The concentrations of these metal species in the effluent water were lower than in the other water bodies.Micro-organic pollutants,xenoestrogens and PACs were analyzed by dual Estrogen and Aryl hydrocarbon Receptor-Chemical Activated LUciferase gene eXpression(ER&AhR-CALUX)assays.Since the annual averaged(AA)bioequivalent concentration of E2(0.18 ng/L)is below the AA-EQS standard(0.4 ng/L),and the bioequivalent concentration of benzo[a]pyrene never exceeded the maximum admissible concentration(MAC),the reclamation and reuse of treated wastewater for groundwater replenishment and agricultural irrigation should pose no environmental problems,at least in a short-term.

Determination of estrogenic activity in the river Chienti(Marche Region, Italy) by using in vivo and in vitro bioassays

Environmental estrogen-like compounds（i.e. xenoestrogens） are a variety of pollutants,ranging from synthetic to natural occurring molecules, that are found in surface and waste waters over a wide range of concentrations. In aquatic environment, the overall estrogenic activity is often due to the presence of a mixture of chemicals and their degraded products which can induce synergistic effects. Current strategies for monitoring estrogen-like chemicals are based on the use of a battery of in vivo and in vitro ecotoxicological tests. In this regard, the aim of the present work was to carry out a bio-monitoring study for testing estrogenicity of the Chienti river（Marche Region, Italy） by using both an E-screen and a vitellogenin（Vtg） induction assay in juvenile goldfish. Three sites were used for analysis,localized at the mouth（sampling point 1）, in the middle（sampling point 2） and at the origin（sampling point 3） of Chienti river. For most of the water samples（i.e. samples collected at sampling points 2 and 3）, clear estrogenic activity was detected in the E-screen assay suggesting different proliferation activities in function of the collecting site. In contrast, the Vtg ELISA demonstrated that water samples collected from each sampling point were estrogenic. Overall, we showed for the first time that the estrogenic activities in water samples from the Chienti river were significant in both in vivo and in vitro; we also observed a different sensitivity between bioassays.

N-acetyl cysteine alters the genotoxic and estrogenic properties of Alternaria toxins in naturally occurring mixtures

It is unclear if complex mycotoxin mixtures produced by Alternaria spp.act estrogenic and/or genotoxic under physiological conditions,particularly considering the co-occurrence with antioxidants in food.Thus,this study focused on enlightening the impact of N-acetyl cysteine(NAC),as a representative antioxidative SH-donor,on the mentioned toxicological endpoints of the signature Alternaria toxins alternariol(AOH),altertoxin-II(ATX-II)and a complex extract(CE)of an Alternaria alternata culture.Using Ishikawa cells as an in vitro model,we monitored alterations in toxin concentrations by LC-MS/MS,estrogenicity by alkaline phosphatase assays,cytotoxicity by sulforhodamine B assays,genotoxicity by single-cell gel electrophoresis and the transcription of selected genes of interest by quantitative realtime PCR.The results indicate that the strong genotoxic effects of epoxide-carrying perylene quinones such as ATX-II are erased in the presence of NAC.The cellular effects of ATX-II/AOH mixtures are dominated by the genotoxicity of the perylene chinone.In this mixture,AOH regained its estrogenicity when coincubated with NAC.In contrast,NAC treatment of an AOH/CE mixture did not result in a recovery of estrogenicity,but in potentiated anti-estrogenic effects.These findings were in line with gene transcription data,that indicated the aryl hydrocarbon receptor(AhR)to be a prime mediator of Alternaria toxin e induced antagonistic effects towards estrogen receptor signaling.Taken together,further studies on potential endocrine-disruptive properties of non-genotoxic perylene quinones should be a future research priority in the field of these emerging contaminants.