Xenoestrogen

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Xenoestrogens are a type of xenohormone that imitates estrogen. They are widely used industrial compounds such as PCB, BPA and Phthalates, that have estrogenic effects on a living organism even though they differ chemically from the naturally occurring estrogenic substances internally produced by the endocrine system of the organism. Their potential ecological and human health impact is currently under extensive study by many scientific institutions and independent researchers[1]. The word xenoestrogen is derived from the Greek words ξένο (xeno, meaning foreign), οἶστρος (estrus, meaning sexual desire) and γόνο (gene, meaning "to generate") and literally means "foreign estrogen". Xenoestrogens are also called "environmental hormones" or "EDC" (Endocrine Disrupting Compounds). Most scientists that study xenoestrogens, including The Endocrine Society, regard them as serious environmental hazards that have hormone disruptive effects on both wildlife and humans[2][3][4][5][6].

As a heterogeneous group of chemicals that are hormonally active agents, xenoestrogens are similar to other estrogens, such as phytoestrogens (estrogenic substances from plants) and mycoestrogens (estrogenic substances from fungi, which can be considered as one type of mycotoxin). Xenoestrogens include pharmacological estrogens (estrogenic action is an intended effect, as in the drug ethinyl estradiol used in contraceptive pill), but other chemicals may also have estrogenic effects. Xenoestrogens have been introduced into the environment by industrial, agricultural and chemical companies and consumers only in the last 70 years or so, but archiestrogens have been a ubiquitous part of the environment even before the existence of the human race given that some plants (like the cereals and the legumes) are using estrogenic substances possibly as part of their natural defence against herbivore animals by controlling their male fertility [1] [7].

Contents

[edit] Effects

Xenoestrogens have been implicated in a variety of medical problems, and during the last 10 years many scientific studies have found hard evidence of adverse effects on human and animal health (external references: [2][3][4][5][6][7][8][9][10][11])[8].

There is a concern that xenoestrogens may act as false messengers and disrupt the process of reproduction. Xenoestrogens, like all estrogens, can increase growth of the endometrium, so treatments for endometriosis include avoidance of products which contain them. Likewise, they are avoided in order to prevent the onset or aggravation of adenomyosis. Studies have implicated observations of disturbances in wildlife with estrogenic exposure. For example, discharge from human settlement including runoff and water flowing out of wastewater treatment plants release a large amount of xenoestrogens into streams, which lead to immense alterations in aquatic life. With a bioaccumulation factor of 10^5 –10^6, fish are extremely susceptible to pollutants [9]. Streams in more arid conditions are thought to have more effects due to higher concentrations of the chemicals arising from lack of dilution [10]

When comparing fish from above a wastewater treatment plant and below a wastewater treatment plant, studies found disrupted ovarian and testicular histopathology, gonadal intersex, reduced gonad size, vitellogenin induction, and altered sex ratios [10].

The sex ratios are female biased because xenoestrogens interrupt gonadal configuration causing complete or partial sex reversal. When comparing adjacent populations of white sucker fish, the exposed female fish can have up to five oocyte stages and asynchronously developing ovaries versus the unexposed female fish who usually have two oocyte stages and group-synchronously developing ovaries. Previously, this type of difference has only been found between tropical and temperate species [10]

Sperm concentrations and motility perimeters are reduced in male fish exposed to xenoestrogens in addition to disrupt stages of spermatogenesis [10][11]. Moreover, xenoestrogens have been leading to vast amounts of intersex in fish. For example, one study indicates the numbers of intersex in white sucker fish to be equal to the number of males in the population downstream of a waste water treatment plant. No intersex members were found upstream from the plant. Also, they found differences in the proportion of testicular and ovarian tissue and it’s degree of organization between the intersex fish [10]. Furthermore, xenoestrogens expose fish to CYP1A inducers through inhibiting a putative labile protein and enhancing the Ah receptor, which has been linked to epizootics of cancer and the initiation of tumors [9].

The induction of CYP1A has been established to be a good bioindicator for xenoestrogen exposure. In addition, xenoestrogens stimulate vitellogenin (Vtg), which acts as a nutrient reserve, and Zona readiata proteins (Zrp), which forms eggshells. Therefore, Vtg and Zrp are biomarkers to exposure for fish [12].

Another potential effect of xenoestrogens is on oncogenes, specifically in relation to breast cancer. Some scientists doubt that xenoestrogens have any significant biological effect, in the concentrations found in the environment.[13] However, there is substantial evidence in a variety of recent studies to indicate that xenoestrogens can increase breast cancer growth in tissue culture.[14][15][16][17]

It has been suggested that very low levels of a xenoestrogen, Bisphenol A, could affect fetal neural signalling more than higher levels, indicating that classical models where dose equals response may not be applicable in susceptible tissue.[18] As this study involved intra-cerebellar injections, its relevance to environmental exposures is unclear, as is the role of an estrogenic effect compared to some other toxic effect of bisphenol A.

Other scientists argue that the observed effects are spurious and inconsistent, or that the quantities of the agents are too low to have any effect.[19] A 1997 survey of scientists in fields pertinent to evaluating estrogens found that 13 percent regarded the health threats from xenoestrogens as "major," 62 percent as "minor" or "none," and 25 percent were unsure.[20]

There has been speculation that falling sperm counts in males may be due to increased oestrogen exposure in utero.[21] Sharpe in a 2005 review indicated that external estrogenic substances are too weak in their cumulative effects to alter male reproductive functioning, but indicates that the situation appears to be more complex as external chemicals may affect the internal testosterone-estrogen balance.[22]

[edit] Presence

The ubiquitous presence of such estrogenic substances is a significant health concern, both individually and for a population. Life relies on the transmission of biochemical information to the next generation, and the presence of xenoestrogens may interfere with this transgenerational information process through "chemical confusion" (Vidaeff and Sever),[23] who state: "The results do not support with certainty the view that environmental estrogens contribute to an increase in male reproductive disorders, neither do they provide sufficient grounds to reject such a hypothesis."

A 2008 report demonstrates further evidence of widespread effects of feminizing chemicals on male development in each class of vertebrate species as a worldwide phenomenon.[24] 99% percent of over 100,000 recently introduced chemicals are underregulated, according to the European Commission.[24]

Agencies such as the United States Environmental Protection Agency and the World Health Organization International Programme on Chemical Safety are charged to address these issues.

[edit] Chemicals shown to have estrogenic effects

[edit] See also

[edit] References

  1. ^ Korach, Kenneth S. (1998). Reproductive and Developmental Toxicology. Marcel Dekker Ltd. pp. 278–279, 294–295. ISBN 978-0824798574. 
  2. ^ Bern HA, Blair P, Brasseur S, Colborn T, Cunha GR, Davis W, Dohler KD, Fox G, Fry M, Gray E, Green R, Hines M, Kubiak TJ, McLachlan J, Myers JP, Peterson RE, Reijnders P.J.H., Soto A, Van Der Kraak G, vom Saal F, Whitten P (1992). "Statement from the Work Session on Chemically-Induced Alterations in Sexual Development: The Wildlife/Human Connection". In Clement C, Colborn T. Chemically-induced alterations in sexual and functional development -- the wildlife/human connection. Princeton, N.J: Princeton Scientific Pub. Co. pp. 1–8. ISBN 0-911131-35-3. http://www.endocrinedisruption.org/files/wingspread_consensus_statement.pdf. 
  3. ^ Bantle J, Bowerman WW IV, Carey C, Colborn T, Deguise S, Dodson S, Facemire CF, Fox G, Fry M, Gilbertson M, Grasman K, Gross T, Guilvlette L Jr., Henny C, Henshel DS, Hose JE, Klein PA, Kubiak TJ, Lahvis G, Palmer B, Peterson C, Ramsay M, White D (May 1995). "Statement from the Work Session on Environmentally induced Alterations in Development: A Focus on Wildlife". Environ. Health Perspect. 103 (Suppl 4): 3–5. doi:10.2307/3432404. JSTOR 3432404. PMC 1519268. PMID 17539108. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1519268. 
  4. ^ Benson WH, Bern HA, Bue B, Colborn T, Cook P, Davis WP, Denslow N, Donaldson EM, Edsall CC, Fournier M, Gilbertson M, Johnson R, Kocan R, Monosson E, Norrgren L, Peterson RE, Rolland R, Smolen M, Spies R, Sullivan C, Thomas P, Van Der Kraak G (1997). "Statement from the work session on chemically induced alterations in functional development and reproduction of fishes". In Rolland RM, Gilbertson M, Peterson RE. Chemically Induced Alterations in Functional Development and Reproduction of Fishes. Society of Environmental Toxicology & Chemist. pp. 3–8. ISBN 1-880611-19-8. 
  5. ^ Alleva E, Brock J, Brouwer A, Colborn T, Fossi MC, Gray E, Guillette L, Hauser P, Leatherland J, MacLusky N, Mutti A, Palanza P, Parmigiani S, Porterfield, Santi R, Stein SA, vom Saal F (1998). "Statement from the work session on environmental endocrine-disrupting chemicals: neural, endocrine, and behavioral effects". Toxicol Ind Health 14 (1–2): 1–8. PMID 9460166. 
  6. ^ Brock J, Colborn T, Cooper R, Craine DA, Dodson SFM, Garry VF, Gilbertson M, Gray E, Hodgson E, Kelce W, Klotz D, Maciorowski AF, Olea N, Porter W, Rolland R, Scott GI, Smolen M, Snedaker SC, Sonnenschein C, Vyas NB, Welshons WV, Whitcomb CE (1999). "Statement from the Work Session on Health Effects of Contemporary-Use Pesticides: the Wildlife / Human Connection". Toxicol Ind Health 15 (1–2): 1–5. 
  7. ^ Infertility in the modern world: present and future prospects, Gillian R. Bentley,C. G. N. Mascie-Taylor, Cambridge University Press, p.99-100
  8. ^ Rogan WJ, Ragan NB (July 2003). "Evidence of effects of environmental chemicals on the endocrine system in children". Pediatrics 112 (1 Pt 2): 247–52. doi:10.1542/peds.112.1.S1.247. PMID 12837917. 
  9. ^ a b Williams, David E., John J Lech, Donald R Buhler. “Xenobiotics and xenoestrogens in fish: modulation of cytochrome P450 and carcinogenesis”. Mutation Research/Fundaental and Molecular Mechanisms of Mutagenesis. 399 (2) (1998): 179-192. Science Direct. 11 February 2010.
  10. ^ a b c d e Vajda, Alan M., Larry B. Barber, James L. Gray, Elena M. Lopez, John D. Woodling, David O. Norris. “Reproductive disruption in fish downstream from an estrogenic wastewater effluent”. Environmental Science Technology. 42 (9) (2008): 3407-3414. 10 February 2010.
  11. ^ Aravindakshan, Jayaprakash, Mary Gregory, David J. Marcogliese, Michel Fournier, Daniel G. Cyr. “Consumption of xenoestrogen-contaminated fish during lactation alters adult male reproductive function”. Toxicological Sciences 81 (1) (2004): 179-189. Oxford Journals. 10 February 2010.
  12. ^ Arukwe, Augustine, Trine Celius, Bernt T. Walterh, Anders Goksoyr. “Effects of xenoestrogen treatment on zona radiata protein and vitellogenin expression in Atlantic salmon”. Aquatic Toxicology 40 (3) (2000):159-170. Science Direct. 10 February 2010.
  13. ^ Golden RJ, Noller KL, Titus-Ernstoff L, Kaufman RH, Mittendorf R, Stillman R, Reese EA (March 1998). "Environmental endocrine modulators and human health: an assessment of the biological evidence". Crit. Rev. Toxicol. 28 (2): 109–227. doi:10.1080/10408449891344191. PMID 9557209. 
  14. ^ Pugazhendhi D, Sadler AJ, Darbre PD (2007). "Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells". J Appl Toxicol 27 (1): 67–77. doi:10.1002/jat.1200. PMID 17121429. 
  15. ^ Buterin T, Koch C, Naegeli H (August 2006). "Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells". Carcinogenesis 27 (8): 1567–78. doi:10.1093/carcin/bgi339. PMID 16474171. 
  16. ^ Darbre PD (March 2006). "Environmental oestrogens, cosmetics and breast cancer". Best Pract. Res. Clin. Endocrinol. Metab. 20 (1): 121–43. doi:10.1016/j.beem.2005.09.007. PMID 16522524. 
  17. ^ Darbre PD, Aljarrah A, Miller WR, Coldham NG, Sauer MJ, Pope GS (2004). "Concentrations of parabens in human breast tumours". J Appl Toxicol 24 (1): 5–13. doi:10.1002/jat.958. PMID 14745841. 
  18. ^ Zsarnovszky A, Le HH, Wang HS, Belcher SM (December 2005). "Ontogeny of rapid estrogen-mediated extracellular signal-regulated kinase signaling in the rat cerebellar cortex: potent nongenomic agonist and endocrine disrupting activity of the xenoestrogen bisphenol A". Endocrinology 146 (12): 5388–96. doi:10.1210/en.2005-0565. PMID 16123166. 
  19. ^ Safe S (December 2004). "Endocrine disruptors and human health: is there a problem". Toxicology 205 (1–2): 3–10. doi:10.1016/j.tox.2004.06.032. PMID 15458784. 
  20. ^ Lichter, SR., Murray, DW. Correspondence. New England Journal of Medicine. 1998 April 2;338(14):988-991.
  21. ^ Sharpe RM, Skakkebaek NE (May 1993). "Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract?". Lancet 341 (8857): 1392–5. doi:10.1016/0140-6736(93)90953-E. PMID 8098802. 
  22. ^ Sharpe RM (February 2003). "The 'oestrogen hypothesis'- where do we stand now?". Int. J. Androl. 26 (1): 2–15. doi:10.1046/j.1365-2605.2003.00367.x. PMID 12534932. 
  23. ^ Vidaeff AC, Sever LE (2005). "In utero exposure to environmental estrogens and male reproductive health: a systematic review of biological and epidemiologic evidence". Reprod. Toxicol. 20 (1): 5–20. doi:10.1016/j.reprotox.2004.12.015. PMID 15808781. 
  24. ^ a b It's official: Men are the weaker sex 7 December 2008. The Independent.

[edit] External links

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