Abstract
Fenitrothion (FN) is a widely used organophosphorous pesticide that has structural similarities with the clinical anti-androgen flutamide. The potential for FN to act as an anti-androgen (at exposures of 1, 50, and 200 μg FN/l over a 26-day period) was assessed in male three-spined sticklebacks, Gasterosteus aculeatus, by measuring kidney spiggin concentration, nest-building, and courtship behavior. Spiggin is the glue protein that male sticklebacks use to build their nests and is directly controlled by androgens. FN exposure significantly reduced spiggin production as well as nest-building activity. It also adversely affected courtship—especially the ‘zigzag dance’ and biting behavior of the males. FN thus appears to have anti-androgenic effects on both the physiology and behavior of the male stickleback.





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Advisory Committee on Pesticides (2006) Evaluation on fenitrothion. Department for Environment, Food and Rural Affairs, Pesticides Safety Directorate, Issue No 225, York, 324 pp
Allen Y, Scott AP, Matthiessen P, Haworth S, Thain JE, Feist S (1999) Survey of estrogenic activity in United Kingdom estuarine and coastal waters and its effects on gonadal development of the flounder Platichthys flesus. Environ Toxicol Chem 18:1791–1800. doi :10.1897/1551-5028(1999)018<1791:SOEAIU>2.3.CO;2
Ankley GT, Jensen KM, Kahl MD, Korte JJ, Makynen EA (2001) Description and evaluation of a short-term reproduction test with the fathead minnow (Pimephales promelas). Environ Toxicol Chem 20:1276–1290. doi :10.1897/1551-5028(2001)020<1276:DAEOAS>2.0.CO;2
Baatrup E, Junge M (2001) Antiandrogenic pesticides disrupt sexual characteristics in the adult male guppy (Poecilia reticulata). Environ Health Perspect 109:1063–1070. doi:10.2307/3454962
Bakker TCM, Sevenster P (1989) Changes in the sexual tendency accompanying selection for aggressiveness in the 3-spined stickleback, Gasterosteus aculeatus L. J Fish Biol 34:233–243. doi:10.1111/j.1095-8649.1989.tb03305.x
Bayley M, Junge M, Baatrup E (2002) Exposure of juvenile guppies to three antiandrogens causes demasculinization and a reduced sperm count in adult males. Aquat Toxicol 56:227–239. doi:10.1016/S0166-445X(01)00210-7
Bayley M, Larsen PF, Baekgaard H, Baatrup E (2003) The effects of vinclozolin, an anti-androgenic fungicide, on male guppy secondary sex characters and reproductive success. Biol Reprod 69:1951–1956. doi:10.1095/biolreprod.103.017780
Bell AM (2001) Effects of an endocrine disrupter on courtship and aggressive behaviour of male three-spined stickleback, Gasterosteus aculeatus. Anim Behav 62:775–780. doi:10.1006/anbe.2001.1824
Bernhardt RR, von Hippel FA (2008) Chronic perchlorate exposure impairs stickleback reproductive behaviour and swimming performance. Behaviour 145:527–559
Bernhardt RR, von Hippel FA, Cresko WA (2006) Perchlorate induces hermaphroditism in threespine sticklebacks. Environ Toxicol Chem 25:2087–2096. doi:10.1897/05-454R.1
Bjerselius R, Lundstedt-Enkel K, Olsen H, Mayer I, Dimberg K (2001) Male goldfish reproductive behaviour and physiology are severely affected by exogenous exposure to 17β-estradiol. Aquat Toxicol 53:139–152. doi:10.1016/S0166-445X(00)00160-0
Björkblom C, Olsson PE, Katsiadaki I, Wiklund T (2007) Estrogen- and androgen-sensitive bioassays based on primary cell and tissue slice cultures from three-spined stickleback (Gasterosteus aculeatus). Comp Biochem Physiol C Toxicol Pharmacol 146:431–442. doi:10.1016/j.cbpc.2007.05.004
Borg B, Antonopoulou E, Andersson E, Carlberg T, Mayer I (1993) Effectiveness of several androgens in stimulating kidney hypertrophy, a secondary sexual character, in castrated male 3- spined sticklebacks, Gasterosteus aculeatus. Can J Zool 71:2327–2329. doi:10.1139/z93-326
Borg B, Mayer I (1995) Androgens and behaviour in the three-spined stickleback. Behaviour 132:1025–1035. doi:10.1163/156853995X00432
Brian JV, Augley JJ, Braithwaite VA (2006) Endocrine disrupting effects on the nesting behaviour of male three-spined stickleback Gasterosteus aculeatus L. J Fish Biol 68:1883–1890. doi:10.1111/j.0022-1112.2006.01053.x
Clotfelter ED, Bell AM, Levering KR (2004) The role of animal behaviour in the study of endocrine-disrupting chemicals. Anim Behav 68:665–676
Crawley MJ (2007) The R book. Wiley, New York
Daxenberger A (2002) Pollutants with androgen-disrupting potency. Eur J Lipid Sci Technol 104:124–130. doi :10.1002/1438-9312(200202)104:2<124::AID-EJLT124>3.0.CO;2-T
Desbrow C, Routledge EJ, Brighty GC, Sumpter JP, Waldock M (1998) Identification of estrogenic chemicals in STW effluent. 1. Chemical fractionation and in vitro biological screening. Environ Sci Technol 32:1549–1558. doi:10.1021/es9707973
Environmental Health Criteria (EHC) (1992) No. 133 Fenitrothion. IPCS INCHEM database. http://www.inchem.org/documents/ehc/ehc/ehc133.htm
Fleming WJ, Grue CE (1981) Recovery of cholinesterase activity in five avian species exposed to dicrothophhos, an organophosphorus pesticide. Pestic Biochem Physiol 16:129–135. doi:10.1016/0048-3575(81)90045-6
Gray LE, Ostby J, Furr J, Wolf CJ, Lambright C, Parks L et al (2001) Effects of environmental antiandrogens on reproductive development in experimental animals. Hum Reprod Update 7:248–264. doi:10.1093/humupd/7.3.248
Gray LE, Wilson VS, Stoker T, Lambright C, Furr J, Noriega N et al (2006) Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int J Androl 29:96–104. doi:10.1111/j.1365-2605.2005.00636.x
Gray MA, Teather KL, Metcalfe CD (1999) Reproductive success and behavior of Japanese medaka (Oryzias latipes) exposed to 4-tert-octylphenol. Environ Toxicol Chem 18:2587–2594. doi :10.1897/1551-5028(1999)018<2587:RSABOJ>2.3.CO;2
Guthrie DM, Muntz WRA (1993) Chapter 4. Role of vision in fish behaviour. In: Pitcher TJ (ed) Behaviour of teleost fishes. Chapman & Hall, London, pp 89–128
Hahlbeck E, Katsiadaki I, Mayer I, Adolfsson-Erici M, James J, Bengtsson B-E (2004) The juvenile three-spined stickleback (Gasterosteus aculeatus L.) as a model organism for endocrine disruption II- kidney hypertrophy, vitellogenin and spiggin induction. Aquat Toxicol 70:311–326. doi:10.1016/j.aquatox.2004.10.004
Hershberger LG, Shipley EG, Meyer RK (1953) Myotrophic activity of 19-nortestosterone and other steroids determined by modified levator ani muscle method. Proc Soc Exp Biol Med 83:175–180
Hoar WS (1962) Hormones and the reproductive behaviour of the male three-spined stickleback (Gasterosteus aculeatus). Anim Behav 10:247–266. doi:10.1016/0003-3472(62)90049-0
Hotchkiss AK, Parks-Saldutti LG, Ostby JS, Lambright C, Furr J, Vandenbergh JG et al (2004) A mixture of the “antiandrogens” linuron and butyl benzyl phthalate alters sexual differentiation of the male rat in a cumulative fashion. Biol Reprod 71:1852–1861. doi:10.1095/biolreprod.104.031674
Howell WM, Black DA, Bortone SA (1980) Abnormal expression of secondary sex characters in a population of mosquitofish, Gambusia affinis holbrooki: evidence for environmentally-induced masculinization. Copeia 1980:676–681
Hutchinson TH, Shillabeer N, Winter MJ, Pickford DB (2006) Acute and chronic effects of carrier solvents in aquatic organisms: a critical review. Aquat Toxicol 76:69–92. doi:10.1016/j.aquatox.2005.09.008
Jakobsson S, Borg B, Haux C, Hyllner SJ (1999) An 11-ketotestosterone induced kidney-secreted protein: the nest building glue from male three-spined stickleback, Gasterosteus aculeatus. Fish Physiol Biochem 20:79–85. doi:10.1023/A:1007776016610
Johnson I, Hetheridge M, Tyler CR (2007) Assessment of (anti-) oestrogenic and (anti-) androgenic activities of final effluents from sewage treatment works. Science report-SC020118/SR, Environment Agency, Bristol, UK, 61 pp
Jolly C, Katsiadaki I, Le Belle N, Mayer I, Dufour S (2006) Development of a stickleback kidney cell culture assay for the screening of androgenic and anti-androgenic endocrine disrupters. Aquat Toxicol 79:158–166. doi:10.1016/j.aquatox.2006.06.005
Jones I, Lindberg C, Jakobsson S, Hellqvist A, Hellman U, Borg B et al (2001) Molecular cloning and characterization of spiggin—an androgen-regulated extraorganismal adhesive with structural similarities to Von Willebrand Factor-related proteins. J Biol Chem 276:17857–17863. doi:10.1074/jbc.M101142200
Katsiadaki I (2007) Chapter 10: the use of the stickleback as a sentinel and model species in ecotoxicology. In: Östlund-Nilsson S, Mayer I, Huntingford FA (eds) Biology of the three-spined stickleback. CRC Press, Boca Raton, pp 319–351
Katsiadaki I, Sanders MB, Sebire M, Nagae M, Soyano K, Scott AP (2007) Threespined stickleback: an emerging model in environmental endocrine disruption. Environ Sci 14:263–283
Katsiadaki I, Scott AP, Hurst MR, Matthiessen P, Mayer I (2002a) Detection of environmental androgens: a novel method based on enzyme-linked immunosorbent assay of spiggin, the stickleback (Gasterosteus aculeatus) glue protein. Environ Toxicol Chem 21:1946–1954. doi :10.1897/1551-5028(2002)021<1946:DOEAAN>2.0.CO;2
Katsiadaki I, Scott AP, Mayer I (2002b) The potential of the three-spined stickleback (Gasterosteus aculeatus L.) as a combined biomarker for oestrogens and androgens in European waters. Mar Environ Res 54:725–728. doi:10.1016/S0141-1136(02)00110-1
Katsiadaki I, Morris S, Squires C, Hurst MR, James JD, Scott AP (2006) Use of the three-spined stickleback (Gasterosteus aculeatus) as a sensitive in vivo test for the detection of environmental antiandrogens. Environ Health Perspect 114(Suppl 1):115–121
Katsiadaki I, Scott AP (2006) The stickleback model in endocrine disruption research: An essential tool in the laboratory and the field. Mar Environ Res 62:S228–S229
Kelce WR, Wilson EM (1997) Environmental antiandrogens: developmental effects, molecular mechanisms, and clinical implications. J Mol Med 75:198–207. doi:10.1007/s001090050104
Kime DE, Nash JP, Scott AP (1999) Vitellogenesis as a biomarker of reproductive disruption by xenobiotics. Aquaculture 177:345–352. doi:10.1016/S0044-8486(99)00097-6
Lambright C, Ostby J, Bobseine K, Wilson V, Hotchkiss AK, Mann PC et al (2000) Cellular and molecular mechanisms of action of linuron: An antiandrogenic herbicide that produces reproductive malformations in male rats. Toxicol Sci 56:389–399. doi:10.1093/toxsci/56.2.389
McCarty J, Secord AL (1999) Nest-building behavior in PCB-contaminated tree swallows. Auk 116:55–63
Morgan MJ, Fancey LL, Kiceniuk JW (1990) Response and recovery of brain acetylcholinesterase activity in Atlantic salmon (Salmo salar) exposed to fenitrothion. Can J Fish Aquat Sci 47:1652–1654
Oshima Y, Kang IJ, Kobayashi M, Nakayama K, Imada N, Honjo T (2003) Suppression of sexual behavior in male Japanese medaka (Oryzias latipes) exposed to 17β-estradiol. Chemosphere 50:429–436. doi:10.1016/S0045-6535(02)00494-0
Páll MK, Mayer I, Borg B (2002a) Androgen and behavior in the male three-spined stickleback, Gasterosteus aculeatus I.—Changes in 11-ketotestosterone levels during the nesting cycle. Horm Behav 41:377–383. doi:10.1006/hbeh.2002.1777
Páll MK, Mayer I, Borg B (2002b) Androgen and behavior in the male three-spined stickleback, Gasterosteus aculeatus II. Castration and 11-ketoandrostenedione effects on courtship and parental care during the nesting cycle. Horm Behav 42:337–344. doi:10.1006/hbeh.2002.1820
Panter GH, Hutchinson TH, Hurd KS, Sherren A, Stanley RD, Tyler CR (2004) Successful detection of (anti-) androgenic and aromatase inhibitors in pre-spawning adult fathead minnows (Pimephales promelas) using easily measured endpoints of sexual development. Aquat Toxicol 70:11–21. doi:10.1016/j.aquatox.2004.06.007
Peakall DB (1996) Disrupted patterns of behavior in natural populations as an index of ecotoxicity. Environ Health Perspect 104:331–335. doi:10.2307/3432653
Purdom CE, Hardiman PA, Bye VVJ, Eno NC, Tyler CR, Sumpter JP (1994) Estrogenic effects of effluents from sewage treatment works. Chem Ecol 8:275–285. doi:10.1080/02757549408038554
Roberts DK, Silvey NJ, Bailey EM (1988) Brain acetylcholinesterase activity recovery following acute methylparathion intoxication in two feral rodent species: Comparison to laboratory rodents. Bull Environ Contam Toxicol 41:26–35. doi:10.1007/BF01689055
Rouse EF, Coppenger CJ, Barnes PR (1977) The effect of an androgen inhibitor on behavior and testicular morphology in the stickleback Gasterosteus aculeatus. Horm Behav 9:8–18. doi:10.1016/0018-506X(77)90045-9
Rowland WJ (2000) Habituation and development of response specificity to a sign stimulus: male preference for female courtship posture in stickleback. Anim Behav 60:63–68. doi:10.1006/anbe.2000.1462
Rowland WJ, Bolyard KJ, Jenkins JJ, Fowler J (1995) Video playback experiments on stickleback mate choice: female motivation and attentiveness to male colour cues. Anim Behav 49:1559–1567. doi:10.1016/0003-3472(95)90077-2
Rowland WJ, Grindle N, Maclaren RD, Granquist R (2002) Male preference for a subtle posture cue that signals spawning readiness in female sticklebacks. Anim Behav 63:743–748. doi:10.1006/anbe.2001.1956
Sanchez W, Katsiadaki I, Piccini B, Ditche J-M, Porcher J-M (2008) Biomarker responses in wild three-spined stickleback (Gasterosteus aculeatus L.) as a useful tool for freshwater biomonitoring: A multiparametric approach. Environ Int 34:490–498. doi:10.1016/j.envint.2007.11.003
Sancho E, Ferrando MD, Andreu E (1997) Response and recovery of brain acetylcholinesterase activity in the European eel, Anguilla anguilla, exposed to fenitrothion. Ecotoxicol Environ Saf 38:205–209. doi:10.1006/eesa.1997.1579
Scott AP, Sorensen PW (1994) Time-course of release of pheromonally active gonadal steroids and their conjugates by ovulatory goldfish. Gen Comp Endocrinol 96:309–323. doi:10.1006/gcen.1994.1186
Scott GR, Sloman KA (2004) The effects of environmental pollutants on complex fish behaviour: integrating behavioural and physiological indicators of toxicity. Aquat Toxicol 68:369–392. doi:10.1016/j.aquatox.2004.03.016
Sebire M, Katsiadaki I (2008) The reproductive behaviour of the three-spined stickleback as a novel assay for the detection of anti-androgens. Cybium 32(2) suppl., 59–60
Scherer E (1975) Avoidance of fenitrothion by goldfish (Carassius auratus). Bull Environ Contam Toxicol 13:492–496. doi:10.1007/BF01721858
Seki M, Yokota H, Matsubara H, Maeda M, Tadokoro H, Kobayashi K (2004) Fish full life-cycle testing for androgen methyltestosterone on medaka (Oryzias latipes). Environ Toxicol Chem 23:774–781. doi:10.1897/03-26
Sohoni P, Lefevre PA, Ashby J, Sumpter JP (2001) Possible androgenic/anti-androgenic activity of the insecticide fenitrothion. J Appl Toxicol 21:173–178. doi:10.1002/jat.747
Sorsa SS, Li S-N, Fang D-F (2000) In vivo inhibition and recovery of brain acetylcholinesterase in topmouth gudgeon (Pseudorasobora parva) following exposure to fenitrothion. J Zhejiang Univ Sci 1:448–455. doi:10.1631/jzus.2000.0448
Sumpter JP (2005) Endocrine disrupters in the aquatic environment: An overview. Acta Hydrochim Hydrobiol 33:9–16. doi:10.1002/aheh.200400555
Sumpter JP, Jobling S (1995) Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment. Environ Health Perspect 103:173–178. doi:10.2307/3432529
Sunami O, Kunimatsu T, Yamada T, Yabushita S, Sukata T, Miyata K et al (2000) Evaluation of a 5-day Hershberger assay using young mature male rats: methyltestosterone and p,p′-DDE, but not fenitrothion, exhibited androgenic or antiandrogenic activity in vivo. J Toxicol Sci 25:403–415
Symons PEK (1973) Behavior of young Atlantic salmon (Salmo salar) exposed to or force-fed fenitrothion, an organophosphate insecticide. J Fish Res Bd Can 30:651–655
Tamura H, Maness SC, Reischmann K, Dorman DC, Gray LE, Gaido KW (2001) Androgen receptor antagonism by the organophosphate insecticide fenitrothion. Toxicol Sci 60:56–62. doi:10.1093/toxsci/60.1.56
Tamura H, Yoshikawa H, Gaido KW, Ross SM, DeLisle RK, Welsh WJ et al (2003) Interaction of organophosphate pesticides and related compounds with the androgen receptor. Environ Health Perspect 111:545–552
Thorpe K, Tyler CR (2005) Oestrogenic Endocrine Disruption in fish—developing biological effect measurement tools and generating hazard data. Science report-SC00043/SR. Environment Agency, Bristol, UK, p 91
Thorpe KL, Hutchinson TH, Hetheridge MJ, Sumpter JP, Tyler CR (2000) Development of an in vivo screening assay for estrogenic chemicals using juvenile rainbow trout (Oncorhynchus mykiss). Environ Toxicol Chem 19:2812–2820. doi :10.1897/1551-5028(2000)019<2812:DOAIVS>2.0.CO;2
Toft G, Baatrup E, Guillette LJ Jr (2004) Altered social behavior and sexual characteristics in mosquitofish (Gambusia holbrooki) living downstream of a paper mill. Aquat Toxicol 70:213–222. doi:10.1016/j.aquatox.2004.09.002
Toft G, Guillette LJ Jr (2005) Decreased sperm count and sexual behavior in mosquitofish exposed to water from a pesticide-contaminated lake. Ecotoxicol Environ Saf 60:15–20. doi:10.1016/j.ecoenv.2004.07.010
Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ Jr et al (1996) Male reproductive health and environmental xenoestrogens. Environ Health Perspect 104(Suppl):741–803. doi:10.2307/3432709
Tyler CR, Jobling S, Sumpter JP (1998) Endocrine disruption in wildlife: a critical review of the evidence. Crit Rev Toxicol 28:319–361. doi:10.1080/10408449891344236
Vos JG, Dybing E, Greim HA, Ladefoged O, Lambre C, Tarazona JV et al (2000) Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation. Crit Rev Toxicol 30:71–133. doi:10.1080/10408440091159176
Wibe AE, Rosenqvist G, Jenssen BM (2002) Disruption of male reproductive behavior in threespine stickleback Gasterosteus aculeatus exposed to 17β-estradiol. Environ Res 90:136–141. doi:10.1006/enrs.2002.4392
Williams K, Fisher JS, Turner KJ, Mckinnell C, Saunders PTK, Sharpe RM (2001) Relationship between expression of sex steroid receptors and structure of the seminal vesicles after neonatal treatment of rats with potent or weak estrogens. Environ Health Perspect 109:1227–1235. doi:10.2307/3454744
Wootton RJ (1976) The biology of the sticklebacks. Academic Press, London
Zala SM, Penn DJ (2004) Abnormal behaviours induced by chemical pollution: a review of the evidence and new challenges. Anim Behav 68:649–664
Acknowledgments
The study was financially supported by the Department for Environment, Food and Rural Affairs (Defra, Grant number CT20051). We thank Dr. I. Barber (University of Leicester) for providing the FIT software. MS is presently funded by a NERC grant to CRT (NER/NE/E016634/1).
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Sebire, M., Scott, A.P., Tyler, C.R. et al. The organophosphorous pesticide, fenitrothion, acts as an anti-androgen and alters reproductive behavior of the male three-spined stickleback, Gasterosteus aculeatus . Ecotoxicology 18, 122–133 (2009). https://doi.org/10.1007/s10646-008-0265-2
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DOI: https://doi.org/10.1007/s10646-008-0265-2


