Summary of endocrine disruption research January to June 2007

Akbas, G.E., X. Fei & H.S. Taylor. (2007). Regulation of HOXA10 expression by phytoestrogens. American Journal of Physiology, Endocrinology and Metabolism 292, E435-E442. PMID: 16985261

Translated Title: Plant based estrogens regulate expression of reproductive gene.        
Conclusions:  In utero exposure to plant estrogens unlikely to result in developmental anomalies due to modification of HOXA10 expression, however, this may be a mechanism by which adult exposure to genistein alters fertility. 

Benninghoff, A.D. (2007). Toxicoproteomics--the next step in the evolution of environmental biomarkers. Toxicological Sciences: An Official Journal of the Society of  Toxicology 95, 1-4. PMID: 17209232  

Translated Title: New technique in biomonitoring called toxicoproteomics holds promise for improving exposure assessment.
Conclusions:  Advances in biomonitoring have led to methods which simultaneously reflect chemical exposure and biological effect. Toxicoproteomics is one such technique in which protein expression profiles are used to indicate xenoestrogen exposure. Although this technique holds promise for improved risk assessment, limitations such as varying protein expression within species and similar methods of action for various pollutants remain.

Birrell, S.N., L.M. Butler, J.M. Harris, G. Buchanan & W.D. Tilley. (2007). Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer. The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology. EPub. PMID: 17413000

Translated Title: Exposure to synthetic progestins may increase risk of breast cancer.
Conclusions: By binding to the androgen receptor, synthetic progestins may be negating the protective effects of androgen signaling in the breast and may account for recent increases in breast cancer.

Brian, J.V., C.A. Harris, M. Scholze, A. Kortenkamp, P. Booy, M. Lamoree, et al. (2007). Evidence of estrogenic mixture effects on the reproductive performance of fish. Environmental Science & Technology 41, 337-344. PMID: 17265968

Translated Title: Mixtures of endocrine disrupting chemicals affects reproduction in fish.
Conclusions: Mixtures of chemicals may have adverse health outcomes even when each component is present below the threshold of detectable effects.

Canesi, L., L.C. Lorusso, C. Ciacci, M. Betti, M. Rocchi, G. Pojana, et al. (2007). Immunomodulation of Mytilus hemocytes by individual estrogenic chemicals and environmentally relevant mixtures of estrogens: in vitro and in vivo studies. Aquatic Toxicology (Amsterdam, Netherlands) 81, 36-44. PMID: 17126923

Translated Title: Individual and mixtures of estrogenic chemicals affect immune system of mollusk species. 
Conclusions: Effects of chemical mixtures were observed on mollusk species, Mytilus, immune parameters both in vitro and in vivo, indicating that these parameters may be used to evaluate estrogenic potential of environmental samples. 

Carbone, P., F. Giordano, F. Nori, A. Mantovani, D. Taruscio, L. Lauria, et al. (2007). The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. International Journal of Andrology 30, 3-13. PMID: 16824044

Translated Title: Study in rural Sicily reveals only possible association between endocrine related chemicals and cryptorchidism and hypospadias. Conclusions: Study reveals very little support for the hypothesis linking cryptorchidism and hypospadias with agricultural exposures as authors did not find a statistically significant increase in risk among parents directly involved in this type of work. A non-statistically significant increase in risk was found for cyrptochidism in mothers employed in agricultural work (OR = 2.97, 95% CI = 0.77-11.47).

Carreno, J., A. Rivas, A. Granada, M. Jose Lopez-Espinosa, M. Mariscal, N. Olea, et al. (2007). Exposure of young men to organochlorine pesticides in Southern Spain. Environmental Research 103, 55-61. PMID: 16889768

Translated Title:  Exposure of young men to pesticides in Southern Spain.
Conclusions: By measuring and comparing levels of 14 organochlorine pesticides (ex: DDT metabolites) in the blood of 220 young males in Southern Spain, it was determined that men of reproductive age are exposed to these chemicals, and further study is warranted to determine the potential health effects of such  exposures.

Ceccarelli, I., D. Della Seta, P. Fiorenzani, F. Farabollini & A.M. Aloisi. (2007). Estrogenic chemicals at puberty change ERalpha in the hypothalamus of male and female rats. Neurotoxicology and Teratology 29, 108-115. PMID: 17157476

Translated Title: Exposures to estrogenic chemicals during puberty affects receptors in the rat brain.
Conclusions: Results of study indicate that estrogenic chemicals have the ability to change the reproductive neural circuits of male and female rats during puberty. 

Charles, G.D., C. Gennings, B. Tornesi, H.L. Kan, T.R. Zacharewski, B. Bhaskar Gollapudi, et al. (2007). Analysis of the interaction of phytoestrogens and synthetic chemicals: an in vitro/in vivo comparison. Toxicology and Applied Pharmacology 218, 280-288.  PMID: 17222880

Translated Title: Analysis of interactions between plant estrogens and synthetic chemicals.
Conclusions: Study reveals that, in vitro, the interactions between high-doses of synthetic chemicals and plant chemicals were greater than additive, but less than additive when plant estrogens were excluded from the mixture. In vivo, the results were consistent with additivity. The authors therefore conclude that chemical mixture toxicity is only likely to be a concern when the components approach individual response thresholds.  

Clewell, R.A., E.A. Merrill, J.M. Gearhart, P.J. Robinson, T.R. Sterner, D.R. Mattie, et al. (2007). Perchlorate and radioiodide kinetics across life stages in the human: using PBPK models to predict dosimetry and thyroid inhibition and sensitive subpopulations based on developmental stage. Journal of Toxicology and Environmental Health Part A 70, 408-428. PMID: 17454566

Translated Title: Effects of drinking water contaminant on thyroid iodide uptake across various human life stages.
Conclusions: Predictive modeling indicated that pregnant women, the fetus and lactating women, had higher blood concentrations of the drinking water contaminant, perchlorate, and in turn higher inhibition of thyroid iodide intake, than non-pregnant women or older children. However, the extent of the inhibition was not significant at the USEPA reference dose.

Courant, F., J.P. Antignac, D. Maume, F. Monteau, A.M. Andersson, N. Skakkebaek, et al. (2007). Exposure assessment of prepubertal children to steroid endocrine disrupters 1. Analytical strategy for estrogens measurement in plasma at ultra-trace level. Analytica Chimica Acta 586, 105-114. PMID: 17386701

Translated Title: New strategy developed for assessing low-level exposure to steroid endocrine disruptors in young children.
Conclusions: By developing a new ultra-sensitive method to detect trace measurements of steroid endocrine disruptors, the authors determined that endogenous levels of estradiol were very low in prepubertal children and thus, exogenous estrogens will constitute a higher proportion of sex hormone activity in children. 

Cravedi, J.P., D. Zalko, J.F. Savouret, A. Menuet & B. Jegou. (2007). The concept of endocrine disruption and human health. Medicine Sciences: M/S 23, 198-204. PMID: 17291431

Translated Title: The concept of endocrine disruption and human health.
Conclusions: Authors review current literature on endocrine disruptors and human health with the aim of describing the present of knowledge surrounding this topic.

Dang, V.H., K.C. Choi, S.H. Hyun & E.B. Jeung. (2007). Analysis of gene expression profiles in the offspring of rats following maternal exposure to xenoestrogens. Reproductive Toxicology (Elmsford, N.Y.) 23, 42-54. PMID: 17011747.

Translated Title: Are genes expressed differently in the offspring of rats exposed to foreign estrogens?
Conclusions: Exposure in the womb to 4-tert-octyphenol (OP) or diethylstillbesterol (DES) may cause temporal changes in gene expression in the uteri of both mothers and offspring.

Ding, L., M.B. Murphy, Y. He, Y. Xu, L.W. Yeung, J. Wang, et al. (2007). Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line. Environmental Toxicology and Chemistry / SETAC 26, 764-772. PMID: 17447562. 

Translated Title: Effects of brominated flame retardants and brominated dioxins on steroid production.
Conclusions: Bromophenol, bromobiphenyls, and bromodibenzo-p-dioxins/furans are capable of altering steroid production via changes in gene expression. This may be one mechanism by which the endocrine system is disrupted by these pollutants.

Janer, G. & C. Porte. (2007). Sex steroids and potential mechanisms of non-genomic endocrine disruption in invertebrates. Ecotoxicology (London, England) 16, 145-160.          PMID: 17219086

Translated Title:  Methods of endocrine disruption in invertebrates excluding alteration of gene expression.
Conclusions: This article presents a review on the presence and metabolism of sex steroids in invertebrates as well as potential mechanisms for endocrine disruption in this group of organisms.

Jefferson, W.N., E. Padilla-Banks & R.R. Newbold. (2007). Disruption of the female reproductive system by the phytoestrogen genistein. Reproductive Toxicology (Elmsford, N.Y.) 23, 308-316. PMID: 17250991.

Translated Title: Plant estrogen, genistein, shown to disrupt female reproductive system.
Conclusions: Exposure to genistein in the womb at environmentally relevant doses was shown to adversely affect reproduction in adulthood.

Jenkins, S., C. Rowell, J. Wang & C.A. Lamartiniere. (2007). Prenatal TCDD exposure predisposes for mammary cancer in rats. Reproductive Toxicology (Elmsford, N.Y.) 23, 391-396. PMID: 17157473

Translated Title: Exposure to dioxin during prenatal development increases susceptibility to mammary cancer in rats.
Conclusions: Seven proteins were shown to be differentially regulated from 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure in the womb. It is believed that these alterations to the mammary proteome can in turn alter susceptibility to mammary cancer later in life.

Jimenez, B., G. Mori, M.A. Concejero, R. Merino, S. Casini & M.C. Fossi. (2007). Vitellogenin and zona radiata proteins as biomarkers of endocrine disruption in peregrine falcon (Falco peregrinus). Chemosphere 67, S375-S378. PMID: 17223181.

Translated Title: Proteins found to be sensitive biomarker of endocrine disruption in falcon species.
Conclusions: Induction of Vtg and Zrp was shown to be an effective tool for detecting exposure to endocrine disrupting chemicals. As well, since increased Vtg and Zrp was detected in the male specimen, there may be cause for concern over the reproductive health of this species.

Kim, H.H., D.H. Kwak, J.M. Yon, I.J. Baek, S.R. Lee, J.E. Lee, et al. (2007). Differential Expression of 3beta-Hydroxysteroid Dehydrogenase mRNA in Rat Testes Exposed to Endocrine Disruptors. The Journal of Reproduction and Development 53, 465-471. PMID: 17229994

Translated Title: mRNA expression altered in rat testes exposed to endocrine disruptors.
Conclusions: The investigators found that testosterone at low doses increased the expression of 3beta-hydroxysteroid dehydrogenase mRNA (3beta-HSD), but down regulated expression at high doses. Other substances including ketoconazole, diethylhexyl phthalate, nonylphenol, octyphenol and diethylstilbersterol all downregulated 3beta-HSD, whereas flutamine increased expression. Overall the authors found that these pollutants have the ability to alter androgen biosynthesis in the testes.  

Kinnberg, K., H. Holbech, G.I. Petersen & P. Bjerregaard. (2007). Effects of the fungicide prochloraz on the sexual development of zebrafish (Danio rerio). Comparative Biochemistry and Physiology.Toxicology & Pharmacology : CBP 145, 165-170. PMID: 17229592

Translated Title: Exposure to fungicide affects sexual development of zebrafish.
Conclusions: The authors found that when zebrafish were exposed to 202 microg/L of prochloraz an increased proportion of males as well as an increased incidence of intersex and altered stages of gonads was observed. At the same exposure level, a decrease in vitellogenin was observed for both males and females however, at lower exposures (16 and 64 microg/L) an increase in vitellogenin was observed in the males. This study provides support for the Fish Sexual Development Test (FSDT).

Lelli, S.M., N.R. Ceballos, M.B. Mazzetti, C.A. Aldonatti & San Martin de Viale,L.C. (2007). Hexachlorobenzene as hormonal disruptor--studies about glucocorticoids: their hepatic receptors, adrenal synthesis and plasma levels in relation to impaired gluconeogenesis. Biochemical Pharmacology 73, 873-879. PMID: 17182006

Translated Title: An examination of hexachlorobenzene’s role as a hormonal disruptor and its potential to impair glucose synthesis.
Conclusions: Authors determined that hexachorobenzene disrupts a group of steroid hormones called glucocorticoids which are characterized by their ability to bind to bind with the cortisol receptor. They also observed disruption of hepatic receptors. Overall, they determined that this pollutant could contribute to a negative effect on glucose synthesis through the enzyme phosphoenolpyruvate-carboxykinase (PEPCK) regulation. 

Lerner, D.T., B.T. Bjornsson & S.D. McCormick. (2007). Effects of aqueous exposure to polychlorinated biphenyls (Aroclor 1254) on physiology and behavior of smolt development of Atlantic salmon. Aquatic Toxicology (Amsterdam, Netherlands) 81, 329-336. PMID: 17275933

Translated Title: Effects of PCB (Aroclor 1254) on salmon development.
Conclusions: Authors determined that the effects of exposure to Aroclor 1254 may vary according to developmental stage.

Liu, B., G. Lin, E. Willingham, H. Ning, C.S. Lin, T. Lue, et al. (2007). Estradiol upregulates activating transcription factor 3, a candidate gene in the etiology of hypospadias. Pediatric and Developmental Pathology: The Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society, 1. PMID: 17378634

Translated Title: Estradiol effects gene that may play a role in the development of hypospadias. 
Conclusions: Ethinyl estradiol upregulates activating transcription factor 3 (ATF3) in fibroblasts in vitro and is likely involved in the development of hypospadias.

Lo, S., I. King, A. Allera & D. Klingmuller. (2007). Effects of various pesticides on human 5alpha-reductase activity in prostate and LNCaP cells. Toxicology in Vitro: An International Journal Published in Association with BIBRA 21, 502-508. PMID: 17218080.

Translated Title: Effects of pesticides on enzyme involved in normal masculinization.
Conclusions: Authors reported on the inhibitory effects/or lack thereof of ten pesticides on human 5 alpha-reductase activity in two different test systems.

Maerkel, K., S. Durrer, M. Henseler, M. Schlumpf & W. Lichtensteiger. (2007). Sexually dimorphic gene regulation in brain as a target for endocrine disrupters: developmental exposure of rats to 4-methylbenzylidene camphor. Toxicology and Applied Pharmacology 218, 152-165. PMID: 17188730

Translated Title: Gene that regulates the systematic difference in form between sexes of the same species in brain, studied as a target for endocrine disruptors in rats. 
Conclusions: Authors found sex and region specific alterations in the regulation of estrogen target genes in the brain, that show effect patterns in baseline and E2 induced gene expression that were different from those different in the uterus and prostate.

Martin, O.V., J.N. Lester, N. Voulvoulis & A.R. Boobis. (2007). Human health and endocrine disruption: a simple multi-criteria framework for the qualitative assessment of endpoint-specific risks in a context of scientific uncertainty. Toxicological Sciences: An Official Journal of the Society of Toxicology. EPub. PMID: 17255114

Translated Title: Human health and endocrine disruption: a framework for assessing endpoint-specific risks when much still remains unknown.
Conclusions:  The authors updated the evidence from the IPCS Global Assessment of the State-of-Science on Endocrine Disruptors through applying three criterion relevant to the Precautionary Principle – Incidence Trends, Association and Consequence. The current degree of knowledge was then ranked according to ignorance, uncertainty, and risk.

Matthiessen, P. & I. Johnson. (2007). Implications of research on endocrine disruption for the environmental risk assessment, regulation and monitoring of chemicals in the European Union. Environmental Pollution (Barking, Essex: 1987) 146, 9-18. PMID: 16996184

Translated Title: Endocrine disruption: environmental risk assessment, chemical regulation and monitoring.
Conclusions:  Research on endocrine disruption in wildlife has indicated a number of flaws in regulating and monitoring chemicals. Although there is no one solution exists in remedying these flaws, the authors recommend that the guiding philosophy should combine chemical and biological solutions to provide: 1) an integrated view of the long-term effects with possibility of multiple causes 2) a predictive view of ecosystem damage and 3) a diagnostic view of causative chemicals.

Merlet, J., C. Racine, E. Moreau, S.G. Moreno & R. Habert. (2007). Male fetal germ cells are targets for androgens that physiologically inhibit their proliferation. Proceedings of the National Academy of Sciences of the United States of America 104, 3615-3620. PMID: 17360691

Translated Title: Cells involved in reproduction are targets for androgens in the developing male fetus.
Conclusions: The authors determined that the germ cells are targets for androgens, and that pathways in the fetal testis during embryonic development are highly     sensitive to anti-androgenic endocrine disruption. 

Murado, M.A. & J.A. Vazquez. (2007). The notion of hormesis and the dose-response theory: a unified approach. Journal of Theoretical Biology 244, 489-499. PMID: 17049945

Translated Title: What to do when the dose-response theory doesn’t work.
Conclusions: The problem of hormesis- that is, when a toxic substance acts like a stimulant in small doses but is an inhibitor at large doses- has been problematic when dealing with traditional dose response theory. To deal with this issue, the authors propose a modification to the dose response theory that allows for biphasic responses.

Nebesio, T.D. & E.A. Eugster. (2007). Current concepts in normal and abnormal puberty. Current Problems in Pediatric and Adolescent Health Care 37, 50-72. PMID: 17223057

Translated Title: A review of the literature on puberty.
Conclusions: This article reviews current concepts in puberty ranging from secular trends and the timing of puberty to variants of precocious puberty as well as pathological precocious puberty, other disorders and delayed puberty.

Newbold, R.R., E. Padilla-Banks, R.J. Snyder, T.M. Phillips & W.N. Jefferson. (2007). Developmental exposure to endocrine disruptors and the obesity epidemic. Reproductive Toxicology (Elmsford, N.Y.) 23, 290-296. PMID: 17321108.

Translated Title:  The relation between endocrine disruptors and obesity.
Conclusions: Authors present a review of the literature that proposes an association of exposure to environmental endocrine disrupting chemicals with the development of obesity. They also describe an animal model of developmental exposure to diethylstilbestrol (DES) to study mechanisms involved in programming an organism for obesity.           

Olea, N. & M. Fernandez. (2007). Endocrine disruption. Journal of Epidemiology and Community Health 61, 372-373. PMID: 17435199.

Translated Title: A review of the literature on endocrine disruption.
Conclusions: The authors believe that current knowledge on endocrine disruption is limited by uncertainties surrounding chronic, low-level and early life exposures. They also identify several knowledge gaps where further research is necessary in order to advance the science.

Price, T.M., S.K. Murphy & E.V. Younglai. (2007). Perspectives: the possible influence of assisted reproductive technologies on transgenerational reproductive effects of environmental endocrine disruptors. Toxicological Sciences: An Official Journal of the Society of Toxicology 96, 218-226. PMID: 17190972

Translated Title: Reproductive technologies may be propagating effects of environmental endocrine disruptors through generations
Conclusions:  The authors review the hypothesis that assisted reproductive technologies are allowing effects of endocrine disruptors to be propagated from individuals that would otherwise be sterile, thus by-passing barriers put in place by natural selection. 

Shi, Z., K.E. Valdez, A.Y. Ting, A. Franczak, S.L. Gum & B.K. Petroff. (2007). Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biology of Reproduction 76, 198-202. PMID: 17050859

Translated Title: Chronic exposure to dioxin leads to ovarian endocrine disruption – one mechanism which may underlie premature loss of function in the reproductive system.
Conclusions: No changes in FSH, LH and progesterone profiles were observed after chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, and the loss of        reproductive cyclicity was not accompanied by a decreased responsiveness to GnRH. Ovarian endocrine disruption was observed to be the primary functional change preceding premature reproductive senescence.

Skinner, M.K. (2007). Endocrine disruptors and epigenetic transgenerational disease etiology. Pediatric Research 61, 48R-50R. PMID: 17413841

Translated Title: Endocrine disruptors and genetic alterations. 
Conclusions:  Prenatal exposures to endocrine disruptors during gonadal sex determination may reprogram male germ-line cells and promote adult-onset disease which may be passed down throughout generations. 

Smith, C.C. & H.S. Taylor. (2007). Xenoestrogen exposure imprints expression of genes (Hoxa10) required for normal uterine development. The FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 21, 239-246. PMID: 17093138

Translated Title: Exposure to foreign estrogens alters expression of gene required for normal uterine development.
Conclusions: Prenatal exposure to Bisphenol A alters the reproductive tract by imprinting essential developmental regulatory genes such as HOXA10 ERE and ARE.

Sun, H., X.L. Xu, L.C. Xu, L. Song, X. Hong, J.F. Chen, et al. (2007). Antiandrogenic activity of pyrethroid pesticides and their metabolite in reporter gene assay. Chemosphere 66, 474-479. PMID: 16857237

Translated Title: Pesticides suppress androgenic activity in vitro.
Conclusions: Using three pyrethroid pesticides (fenvalerate, cypermethrin, permethrin) and their metabolite, along with a human androgen receptor mediated luciferase reporter gene assay, the authors demonstrated that all chemicals analyzed suppressed luciferase expression but none showed androgenic activity.  

Uzumcu, M. & R. Zachow. (2007). Developmental exposure to environmental endocrine disruptors: Consequences within the ovary and on female reproductive function. Reproductive Toxicology (Elmsford, N.Y.) 23, 337-352. PMID: 17140764

Translated Title: Effects of development exposures to environmental endocrine disruptors on the ovary and female reproductive function.
Conclusions: Review suggests that developmental exposure to environmental endocrine disruptors causes not only reproductive anomalies in adulthood, but that these anomalies may be passed down to future generations.

Weiss, B. (2007). Can endocrine disruptors influence neuroplasticity in the aging brain? Neurotoxicology. EPub. PMID: 17350099.

Translated Title: Can endocrine disruptors influence the brain’s natural ability to form new connections as people age?
Conclusions: Authors suggest that exposure to environmental contaminants as well as changing levels of gonadal steroids, may impair the generation of neural pathways, and as a result may impair cognitive function later in life.