Hormone Disrupting Chemicals

Transcription

1 Hormone Disrupting Chemicals

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3 Sperm cells 10 6 per ml

4 Intersex

5 Intersex in British Perch populations Jobling et al. 1998

6 Intersex Roach (Jobling et al, 2002)

7 Intersex Roach (Jobling et al, 2002)

8 Xenoestrogens are chemically diverse

9 Xenoestrogen activity a result of 3D structure?

10 A Model of an intracellular receptor Inhibitory protien complex COOH Hormone binding site Transcriptionactivating domain H 2 N Hinge region DNA-binding domain H 2 N COOH

11 The estrogen receptor domains Activating function 1 Nuclear Localisation signal Activating function 2 A/B C D E F DNA binding domain Hinge region Ligand binding domain Agonist binding domain Antagonist binding domain Homology between Human and Rainbow trout ER A/B: 20% C: 92% E: 60% Mathews et al. 2001

12 Vitellogenin synthesis as a biomarker of estrogenic activity in water Gonadotropins 1 Estrogen 2 3 Liver Ovary 4 5 Vitellogenin

13 Hormone disruption mechanisms Hormone synthesis Hormone secretion Hormone transport Receptor binding Receptor complex mediated transcription Hormone elimination -ve/+ve feedback loops

14 (Arukwe, 2001)

15 Steroid Pathways Made Simple Cholesterol P450 enzymes Xenoandrogens Progestogens Corticoids Androgens Estrogens Aromatase inhibitors

16 Androgen Effects Fish caught below an american Pulp mill Normal female Partly masculinised female Female with advanced masculinisation Normal male

17 Anti-Oestrogen effects Aromatase inhibition Receptor Crosstalk Between two intracellular receptors: Arylhydrocarbon receptor (AhR) & ER receptor AhR causes synthesis of P450 enzyme EROD ER induces production of vitellogenin in fish

18 Vitellogenin production in juvenile Coho salmon

19 Level of organization Effect Population Number of offspring Sex ratio Organism Organ Cell Time to maturation Sexual behaviour Colouration Testis size Gonopodial length Sperm count Molecule

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21 The Guppy Mating System Highly promiscuous Continuous reproduction Viviparous, sperm-counts possible Female choice, male ornamentation display / courtship behaviour. Handicap models... Good gene models... Two different male mating strategies... Full display / Sneaky matings

22 Colouration index Gonopodial index

23 The sigmoid display Female Male

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25 ε δ a ϕ b c ω frame (n) frame (n+1)

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28 Effects of antiandrogens Cl O Cl Cl O N Cl O Vinclozolin Cl p,p -DDE Cl Cl O O O Cl O OH N OH N HO N NO 2 Cl Cl O CF 3 M1 M2 Hydroxyflutamide

29 Effects of antiandrogens - exposure of adults Sperm count Gonadosomatic Index Courtship Behaviour FLU 10 µg/mg FLU 1.0 µg/mg DDE 1.0 µg/mg *** * * *** *** *** *** *** *** DDE 0.1 µg/mg * *** VIN 10 µg/mg VIN 1.0 µg/mg *** *** *** Control Sperm cells (mill.) Testis weight (%) Number of sigmoid displays (10 min) Foetus Juvenile Adult 30 days

30 Effects of antiandrogens - exposure of juveniles Sperm count Gonadosomatic Index Courtship Behaviour FLU 1.0 µg/mg FLU 0.01 µg/mg * * DDE 0.1 µg/mg DDE 0.01 µg/mg VIN 10 µg/mg VIN 0.1 µg/mg Control *** *** ** * * * Sperm cells (mill.) Testis weight (%) Number of sigmoid displays (10 min) Foetus Juvenile Adult

31 Sex ratio after exposure of juveniles to antiandrogens FLU 1.0 µg/mg FLU 0.01 µg/mg DDE 0.1 µg/mg DDE 0.01 µg/mg VIN 10.0 µg/mg VIN 0.1 µg/mg CONTROL % males and % females (n=50) Foetus Juvenile Adult

32 Effects of antiandrogens on the reproductive output FLU 1.0 µg/mg FLU 0.01 µg/mg DDE 0.1 µg/mg DDE 0.01 µg/mg VIN 10.0 µg/mg VIN 0.1 µg/mg CONTROL Average number of offspring per female

33 Conclusions Estrogenic and antiandrogenic chemicals alter male sexual Characteristics Sexual behaviour, Coloration, Sperm production and display coloration are particularly vulnerable to antiandrogens Do these effects translate into reductions in fitness?

34 Vinclozolins effects on Reproduction Effects on male fitness? Effects on female fitness? Effects during pregnancy?

35 Guppy Reproduction Virgin + (30) male fitness traits (Sigmoid,, sperm) Size of virgin females first clutch Virgin (30) + Size of virgin females first clutch (pregnancy) + Size of virgin females first clutch

36 Number sigmoid displays per 10 min Male sexual display * 0,0 0,1 1,0 10,0 Vinclozolin dose µg/mg dry feed Foetus Juvenile Adult ca. 30 days

37 Sædtal (millioner celler pr. han) 3,50 3,00 2,50 2,00 1,50 1,00 The effect of vinclozolin on sperm count ** *** 0,0 0,1 1,0 10,0 Vinclozolin dosis µg/mg tør foder Foetus Juvenile Adult ca. 30 days

38 Effect of vinclozolin on male fitness 20 Number of juveniles per akvarium * ** 2 0,0 0,1 1,0 10,0 Vinclozolin dose µg/mg dry feed Foetus Juvenile Adult ca. 30 days

39 Number of juveniles per male Male sperm count (millioner)

40 Guppy Reproduction Virgin + (30) male fitness traits (Sigmoid,, sperm) Size of virgin females first clutch Virgin (30) + Size of virgin females first clutch (pregnancy) + Size of virgin females first clutch

41 Exponering af gravid hunner 35 Antal juvenile per akvarium ,0 0,1 1,0 10,0 Vinclozolin dosis µg/mg tør foder

42 Guppy Reproduction Virgin + (30) male fitness traits (Sigmoid,, sperm) Size of virgin females first clutch Virgin (30) + Size of virgin females first clutch?? (pregnancy) + Size of virgin females first clutch

43 Fitness?? Microsatellites and male competition experiments Use of genetic markers for assessing sex