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  • 1.
    Archer, Amena
    et al.
    Karolinska Institutet.
    Kitambi, Satish Srinivas
    Karolinska Institutet.
    Hallgren, Stefan
    Södertörns Universitet.
    Pedrelli, Mateo
    Karolinska Institutet.
    Olsén, Håkan
    Södertörns Högskola.
    Agneta, Mode
    Karolinska Institutet.
    Gustafsson, Jan-Åke
    Karolinska Institutet.
    The liver X receptor (lxr) governs lipid homeostasis in zebrafish during development2012In: Open Journal of Endocrine and Metabolic Diseases, ISSN 2165-7432, Vol. 2, p. 74-81Article in journal (Refereed)
    Abstract [en]

    The liver X-receptors (LXRs) act as cholesterol sensors and participate in the regulation of lipid and cholesterol metabolism. The objective of this study was to determine the role of LXR during development using the zebrafish model. By in situ hybridization we showed distinct expression of lxr in the brain and the retina in the developing and adult zebrafish. Lxr ligand activation affected the expression of genes involved in lipid metabolism in zebrafish adult brain and eye as well as in zebrafish embryos. Morpholino knock down of lxr resulted in an overall impaired lipid deposition as determined by oil red O staining particularly in the head and around the eyes, and to significantly elevated levels of both total and free cholesterol in the yolk of lxr morphant embryos. The expression of genes involved in lipid and cholesterol metabolism was also changed in the lxr morphants. Furthermore, alcian blue staining revealed malformation of the pharyngeal skeleton in the lxr morphant. Our data show that lxr is an important component of the regulatory network governing the lipid homeostasis during zebrafish development, which in turn may support a role of lxr for normal development of the central nervous sytem, including the retina.

  • 2.
    Caspillo-Reyhanian, Nasim
    et al.
    Södertörns Högskola.
    Kristina, Volkova
    Södertörns Högskola.
    Stefan, Hallgren
    Södertörns Högskola.
    Per-Erik, Olsson
    Örebro Universitet.
    Inger, Porsch-Hällström
    Södertörns Högskola.
    Short-term treatment of adult male zebrafish (Danio Rerio) with 17α-ethinyl estradiol affects the transcription of genes involved in development and male sex differentiation2014In: Comparative Biochemistry and Physiology Part C: Comparative Pharmacology and Toxicology, ISSN 0742-8413, E-ISSN 1878-1942, Vol. 164, p. 35-42Article in journal (Refereed)
  • 3.
    Hallgren, Stefan
    Södertörns Högskola.
    Brain Aromatase in the Guppy (Poecilia reticulata): Behaviour, Regulation and Spatial distribution2008Conference paper (Other academic)
  • 4.
    Hallgren, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Södertörns Högskola.
    Effects of an endocrine disruptor on anxiety behaviour in fish: Examples from zebrafish and guppy2013In: International Behavioral Neuroscience Society: Annual Meeting Program and Abstracts, 2013, p. 32-33Conference paper (Refereed)
    Abstract [en]

    Animal behaviours such as foraging, predator avoidance, migration, exploration and reproduction are all essential for the survival of the individual as well as the population. Behaviours are integrated end-points of several physiological factors affected by the biotic, social and a-biotic environment, and involves the central nervous system, muscular control, the different senses and a number of hormones. Anthropogenic chemicals released from e.g. agriculture, industrial production, forestry and sewage treatment may interfere with these physiological processes and ultimately cause disturbances in animal behaviour. Disruption of the endocrine system has caught much attention in aquatic toxicology, with much focus on disruption of reproductive behaviour and fertility of exposed fishes. However, mammalian examples suggest that the hormonal axis dealing with the coping of stress (Hypothalamo-Pituitary-Adrenal axis) also is very sensitive to endocrine disruptors. Tests examining stress related behaviours such as fear, anxiety, shoaling and exploration have recently been developed for fish models such as zebrafish. These tests have been suggested as useful tools in development of new psychoactive pharmaceuticals but can also be applied to behaviour toxicology . Our studies using two of these behaviour tests, the novel tank diving test and shoaling test, on Zebrafish and Guppy show that low doses of the synthetic oestrogen Ethynylestradiol-17α can affect both anxiety and shoal adhesive behaviour of exposed fish. We suggest that in fishes the susceptibility to potent endocrine disruptors in stress related behaviours is equal to that of reproductive end-points. 

  • 5. Hallgren, Stefan
    Reduction of brain aromatase activity reduces two courtship behaviours in the male endler guppy (Poecilia reticulata).2006Conference paper (Other academic)
  • 6.
    Hallgren, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    More signs of neurotoxicity of surfactants and flame retardants - Neonatal PFOS and PBDE 99 cause transcriptional alterations in cholinergic genes in the mouse CNS2015In: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 40, no 2, p. 409-416Article in journal (Refereed)
    Abstract [en]

    Maternally and lactionally transferred persistent organic pollutants may interfere with CNS development. Here, 10-day-old male mice were exposed to single oral doses of PFOS (perflourooctanosulphonate) or PBDE 99 (2,2',4,4',5-penta-bromodiphenyl ether), and examined for changes in cholinergic gene transcription in the CNS 24 h and 7 weeks later. 24 h after exposure qPCR analyses revealed decreased transcription of nAChR-beta 2 and AChE in cortex, and increased mAChR-5 in hippocampus of PFOS treated mice. Neonatal PFOS treatment altered spontaneous behaviour at 2 months of age but did not affect gene transcription in adults. At 2 months of age neonatally PBDE 99 treated mice had altered spontaneous behaviour, and cortical transcription of AChE, nAChR-alpha 4, nAChR-beta 2 and mAChR-5 were elevated. Our results indicate that PFOS and PBDE 99 affects the developing central cholinergic system by altering gene transcription in cortex and hippocampus, which may in part account for mechanisms causing changes in spontaneous behaviour.

  • 7.
    Hallgren, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Uppsala University.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Transcriptional alterations of cholinergic and dopaminergic genes in the CNS of mice neonatally exposed to PFOS and PBDE99.2015Conference paper (Other academic)
  • 8.
    Hallgren, Stefan
    et al.
    Södertörns Högskola.
    Kitambi, Satish Srinivas
    Karolinska Institutet.
    Anatomical Distribution of Brain Aromatase (CYP19B) Expression in the Guppy, Poecilia reticulata.2009Conference paper (Other academic)
  • 9.
    Hallgren, Stefan L E
    et al.
    Södertörns Högskola.
    Linderoth, Maria
    Stockholms Universitet.
    Olsén, K Håkan
    Södertörns Högskola.
    Inhibition of cytochrome p450 brain aromatase reduces two male specific sexual behaviours in the male Endler guppy (Poecilia reticulata).2006In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 147, no 3, p. 323-8Article in journal (Refereed)
    Abstract [en]

    In mammalian and avian vertebrate groups, androgens act as controlling agents on male aggression and courtship behaviour by their conversion to oestrogens by cytochrome P450 aromatase in well-defined brain regions. Despite the fact that bony fishes have exceptionally high brain aromatase activity, little is known about it's possible regulatory effects on the reproductive behaviours of teleosts. In this study, Endler guppy males (Poecilia reticulata) were subjected to 26-29 days of 24-h exposure to two different concentrations (15 and 100 microg/L) of the aromatase inhibitor fadrozole in the water. Compared with the control males, two of three courtship activities in males exposed to the higher concentration were reduced when they were paired with receptive stimulus females. Reduction in brain aromatase activity was confirmed in both exposed groups with the use of the tritiated water assay.

  • 10.
    Hallgren, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Lee, Iwa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Buratovic, Sonja
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Adult dose-response-related behavioral effects of 4 different pesticides, after neonatal exposure2014Conference paper (Other academic)
    Abstract [en]

    There are several different types of pesticides globally used, all with their own characteristics and toxicological potency. In the present study we have exposed male mice neonatally to different doses of four different types of pesticides, carbaryl (carbamate) chlorpyrifos (organophosphate), cypermethrin (pyrethroid) and endosulfan (organochlorine), and tested them for spontaneous behavior in a novel home environment at adult age. The doses used were 0.5 – 20 mg carbaryl/kg bw, 0.1 – 5.0 mg chlorpyrifos/kg bw, 0.1 – 5.0 mg cypermethrin/kg bw and 0.05 – 20 mg endosulfan/kg bw. All four pesticides induced adult disturbances in the spontaneous behavior in a novel home environment, affecting cognitive function, at 2 months of age. Carbaryl induced a dose-response related effect on spontaneous behavior from 5 mg/kg bw and up, while chlorpyrifos only induced a weak effect with the highest dose tested (5 mg/kg bw). The pyrethroid cypermethrin induced dose-response related neurotoxicity from 0.5 mg/kg bw and up. The organochlorine endosulfan also induced dose-response related neurotoxicity from 0.1 mg/kg bw and up These disturbances also persisted when the animals were re-observed at 4 months of age, indicating that these effects are long-lasting or even irreversible. From this study we conclude that endosulfan seem to be the most potent, of these four compounds, to induce cognitive behavioral effects in the adult after neonatal exposure, while carbaryl has the lowest potency to induce these types of neurotoxic effects. 

  • 11.
    Hallgren, Stefan
    et al.
    Södertörns Högskola.
    Olsén, K Håkan
    Södertörns Högskola.
    Effects on guppy brain aromatase activity following short-term steroid and 4-nonylphenol exposures.2010In: Environmental Toxicology, ISSN 1520-4081, E-ISSN 1522-7278, Vol. 25, no 3, p. 261-71Article in journal (Refereed)
    Abstract [en]

    Brain estrogen production, performed by the enzyme aromatase, can be disrupted/affected in teleost fish exposed to endocrine disruptors found in polluted aquatic environments. The guppy (Poecilia reticulata) was previously studied and confirmed to suffer negative effects on reproductive behaviors following inhibition of the brain aromatase reaction. Here adult guppies (Poecilia reticulata) of both genders were subjected to known endocrine disruptors: the androgen androstenedione (A), the synthetic estrogen 17alpha-ethinylestradiol (EE(2)), and the estrogenic surfactant 4-nonylphenol (NP), at high (50 microg/L) and at environmentally relevant concentrations (10 ng/L EE(2), 5 microg/L NP, and 0.7 microg/L A) for 2 weeks followed by measurements of brain aromatase activity (bAA). In the adult males, bAA was stimulated by A and EE(2) at 50 microg/L. Female activity was also stimulated by the higher estrogenic treatment. At environmentally relevant concentrations only the EE(2) treatment affected bAA, and only in males. The alkylphenolic substance NP produced no effect in either of the experiments, not on males nor females. The results indicate that short-term steroid treatments have stimulatory effects on guppy brain aromatase even at concentrations that can be found in the environment. We thus suggest bAA of adult guppies to be a suitable bioindicator of endocrine disruptors.

  • 12.
    Hallgren, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Dept. of Organism Biology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Postnatal exposure to PFOS, but not PBDE 99, disturb dopaminergic gene transcription in the mouse CNS2016In: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 41, p. 121-126Article in journal (Refereed)
    Abstract [en]

    The CNS of breast feeding infants and toddlers may be exposed to persistent organic pollutants via lactational transfer. Here, 10 days old mice were exposed to single oral doses of either PFOS, PBDE99 or vehicle control and were examined for changes in dopaminergic gene transcription in CNS tissue collected at 24 h or 2 months post exposure.qPCR analyses of brain tissue from mice euthanized 24 h post exposure revealed that PFOS affected transcription of Dopamine receptor-D5 (DRD5) in cerebral cortex and Tyrosine hydroxylase (TH) in the hippocampus. At 2 months of age, mice neonatally exposed to PFOS displayed decreased transcription of Dopamine receptor-D2 (DRD2) and TH in hippocampus. No significant changes in any of the tested genes were observed in PBDE99 exposed mice. This indicates that PFOS, but not PBDE99, affects the developing cerebral dopaminergic system at gene transcriptional level in cortex and hippocampus, which may account for some of the mechanistic effects behind the aetiology of neuropsychiatric disorders.

  • 13.
    Hallgren, Stefan
    et al.
    Södertörns Högskola.
    Volkova, Kristina
    Reyhanian, Nasim
    Olsén, K Håkan
    Hällström, Inger Porsch
    Anxiogenic behaviour induced by 17α-ethynylestradiol in male guppies (Poecilia reticulata).2011In: Fish Physiology & Biochemistry, ISSN 0920-1742, E-ISSN 1573-5168, Vol. 37, no 4, p. 911-8Article in journal (Refereed)
    Abstract [en]

    Behaviour studies are used in toxicology research as they are excellent tools to measure physiological end-points caused by exogenous chemicals. In mammals both reproductive and non-reproductive behaviours have been used for a long period of time, whereas in teleost fishes non-reproductive behaviours have received little attention compared to reproductive behaviours. Recent advances in measuring stress related behaviours in zebrafish have provided additional tools to understand behaviour toxicology in fish. One species with well documented reproductive behaviour disturbed by different toxicants is the guppy, which is better suited than zebrafish for reproductive behaviour studies and therefore might be a better model organism for comparative behaviour studies in fish toxicology. Here we report new applications for non-reproductive behaviours in guppy and test these behaviours on males treated with the endocrine disruptor 17α-ethynylestradiol at environmentally relevant concentrations. 17α-ethynylestradiol increased freezing and bottom-dwelling when fish were placed in a non-familiar aquarium, but did not significantly affect shoaling behaviour. These results are similar to the anxiogenic behaviours seen in rats treated perinatally with 17α-ethynylestradiol and add more concern to the impacts of endocrine disruptors on aquatic wildlife.

  • 14.
    Kellner, Martin
    et al.
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, Sodertorn, Sweden.
    Porseryd, Tove
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, Sodertorn, Sweden.
    Hallgren, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Porsch-Hällström, Inger
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, Sodertorn, Sweden.
    Hansen, S.H.
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-1168 Copenhagen, Denmark.
    Olsén, K. Håkan
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, Sodertorn, Sweden.
    Waterborne citalopram has anxiolytic effects and increases locomotor activity in the three-spine stickleback (Gasterosteus aculeatus)2016In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 173, p. 19-28Article in journal (Refereed)
    Abstract [en]

    Citalopram is an antidepressant drug, which acts by inhibiting the re-uptake of serotonin from the synaptic cleft into the pre-synaptic nerve ending. It is one of the most common drugs used in treatment of depression, it is highly lipophilic and frequently found in sewage treatment plant effluents and surface waters around the world. Citalopram and other selective serotonin re-uptake inhibitors have, at concentrations that occur in nature, been shown to have behavioural as well as physiological effects on fish and other animals. This study is the result of several different experiments, intended to analyse different aspects of behavioural effects of chronic citalopram exposure in fish. Our model species the three-spine stickleback is common in the entire northern hemisphere and is considered to be a good environmental sentinel species. Female three-spine sticklebacks were exposed to 0, 1.5 and 15 μg/l nominal concentrations of citalopram for 21 days and subjected to the novel tank (NT) diving test. In the NT test, the fish exposed to 1.5 μg/l, but not the 15 μg/l fish made a significantly higher number of transitions to the upper half and stayed there for significantly longer time than the fish exposed to 0 μg/l. The 15 μg/l group, however, displayed a significantly lower number of freeze bouts and a shorter total freezing time. The test for locomotor activity included in the NT test showed that fish treated with 1.5 and 15 μg/l displayed a significantly higher swimming activity than control fish both 5–7 and 15–17 minutes after the start of the experiment. In the next experiment we compared fish exposed to 1.5 μg/l and 0.15 μg/l to pure water controls with regard to shoaling intensity and found no effect of treatment. In the final experiment the propensity of fish treated with 1.5 μg/l to approach an unknown object and aggressive behaviour was investigated using the Novel Object test and a mirror test, respectively. The exposed fish ventured close to the unknown object significantly more often and stayed there for significantly longer time than unexposed fish. The aggression test yielded no statistically significant effects. It is concluded that citalopram changes the behaviour of the three-spine stickleback in a way that is likely to have ecological consequences and that it must not be considered an environmentally safe pharmaceutical.

  • 15.
    Olsén, Håkan
    et al.
    Södertörns Högskola.
    Ask, Katarina
    Södertörns Högskola.
    Olsén, Hanna
    Södertörns Högskola.
    Porsh-Hällström, Inger
    Södertörns Högskola.
    Hallgren, Stefan
    Södertörns Högskola.
    Effects of the SSRI citalopram on behaviours connected to stress and reproduction in Endler guppy, Poecilia wingei.2014In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 148, p. 113-121Article in journal (Refereed)
  • 16.
    Reyhanian, Nasim
    et al.
    Södertörns Högskola.
    Volkova, Kristina
    Södertörns Högskola.
    Hallgren, Stefan
    Södertörns Högskola.
    Bollner, Tomas
    Södertörns Högskola.
    Olsson, Per-Erik
    Örebro Universitet.
    Olsén, Håkan
    Södertörns Högskola.
    Porsch-Hällström, Inger
    Södertörns Högskola.
    17α-ethynyl estradiol affect anxiety and shoaling behavior in adult zebra fish (Danio rerio).2011In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 104, no 1-2, p. 41-48Article in journal (Refereed)
    Abstract [en]

    Ethinyl estradiol is a potent endocrine disrupting compound in fish and ubiquitously present in the aquatic environment. In this study, we exposed adult zebra fish (Danio rerio) males to 0, 5 or 25 ng Ethinyl estradiol/L for 14 days and analyzed the effects on non-reproductive behavior. Effects of treatment of the exposed males was shown by vitellogenin induction, while brain aromatase (CYP 19B) activity was not significantly altered. Both concentrations of Ethinyl estradiol significantly altered the behavior in the Novel tank test, where anxiety is determined as the tendency to stay at the bottom when introduced into an unfamiliar environment. The effects were, however, opposite for the two concentrations. Fish that were exposed to 5 ng/L had longer latency before upswim, fewer transitions to the upper half and shorter total time spent in the upper half compared with control fish, while 25 ng Ethinyl estradiol treatment resulted in shorter latency and more and longer visits to the upper half. The swimming activity of 25, but not 5 ng-exposed fish were slightly but significantly reduced, and these fish tended to spend a lot of time at the surface. We also studied the shoaling behavior as the tendency to leave a shoal of littermates trapped behind a Plexiglas barrier at one end of the test tank. The fish treated with Ethinyl estradiol had significantly longer latency before leaving shoal mates and left the shoal fewer times. Further, the fish exposed to 5 ng/L also spent significantly less time away from shoal than control fish. Fertilization frequency was higher in males exposed to 5 ng/L Ethinyl estradiol when compared with control males, while no spawning was observed after treatment with 25 ng/L. The testes from both treatment groups contained a normal distribution of spermatogenesis stages, and no abnormality in testis morphology could be observed.

    In conclusion, we have observed effects on two behaviors not related to reproduction in zebra fish males after treatment with Ethinyl estradiol, adding to the ecological consequences of contamination of aquatic environments with estrogenic substances.

  • 17.
    Viberg, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Hallgren, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Hamberg, Pierre
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Transcriptional alterations of cholinergic and dopaminergic genes in mice neonatally exposed to the combination of the pesticides carbaryl and chlorpyrifos2016Conference paper (Other academic)
  • 18.
    Volkova, Kristina
    et al.
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden.;Univ Orebro, Sch Sci & Technol, Orebro Life Sci Ctr, SE-17082 Orebro, Sweden..
    Caspillo, Nasim Reyhanian
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden.;Univ Orebro, Sch Sci & Technol, Orebro Life Sci Ctr, SE-17082 Orebro, Sweden..
    Porseryd, Tove
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden..
    Hallgren, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden..
    Dinnetz, Patrik
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden..
    Olsen, Hakan
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden..
    Hallstrom, Inger Porsch
    Sodertorn Univ, Sch Nat Sci Technol & Environm Studies, SE-14186 Huddinge, Sweden..
    Transgenerational effects of 17 alpha-ethinyl estradiol on anxiety behavior in the guppy, Poecilia reticulata2015In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 223, p. 66-72Article in journal (Refereed)
    Abstract [en]

    Environmental contaminants can cause alterations that can be transgenerationally transmitted to subsequent generations. Estrogens are among those contaminants shown to induce heritable changes that persist over generations in mammals. Results in other vertebrates are few. We have analyzed the effects on anxiety of 17 alpha-ethinyl estradiol (EE2) in the F1 and F2 generations in guppies, Poecilia reticulate, obtained from F0 fish maternally exposed to 0 or 20 ng/L EE2 until birth. F0 males and females were bred with fish of the same treatment but different families producing F1 offspring. Behavior in the novel tank test at 6 months revealed that males with EE2-exposed parents had significantly longer latency to the upper half of the tank than control males, while no EE2 effects were observed in females. Also in F2, obtained from F1 as above, males in the EE2 group had longer latency time compared to control males, with no differences due to EE2-exposure of F0 observed in females. In the scototaxis (light/dark preference) test, latency to first transition to black compartment and total transitions to black were significantly altered in females due to EE2 exposure of F0 while the total time in black was higher in males with EE2-exposed F0 compared with controls. The increased anxiety in the F2 generation demonstrates a transgenerational anxiety phenotype and shows that non-reproductive behavior can be transgenerationally modified by estrogens in fish.

  • 19. Volkova, Kristina
    et al.
    Reyhanian Caspillo, Nasim
    Porseryd, Tove
    Hallgren, Stefan
    School of Natural Sciences, Technology and Environmental Studies, Södertörn University.
    Dinnetz, Patrik
    Porsch-Hällström, Inger
    Developmental exposure of zebrafish (Danio rerio) to 17α-Ethinylestradiol affects non-reproductive behavior and fertility as adults, and increases anxiety in unexposed progeny2015In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 73, p. 30-38Article in journal (Refereed)
    Abstract [en]

    Exposure to estrogenic endocrine disruptors (EDCs) during development affects fertility, reproductive and non-reproductive behavior in mammals and fish. These effects can also be transferred to coming generations. In fish, the effects of developmental EDC exposure on non-reproductive behavior are less well studied. Here, we analyze the effects of 17α-ethinylestradiol (EE2) on anxiety, shoaling behavior and fertility in zebrafish after developmental treatment and remediation in clean water until adulthood. Zebrafish embryos were exposed from day 1 to day 80 post fertilization to actual concentrations of 1.2 and 1.6 ng/L EE2. After remediation for 82 days non-reproductive behavior and fertilization success were analyzed in both sexes. Males and females from the 1.2 ng/L group, as well as control males and females, were bred, and behavior of the untreated F1 offspring was tested as adults.

    Developmental treatment with 1.2 and 1.6 ng/L EE2 significantly increased anxiety in the novel tank test and increased shoaling intensity in both sexes. Fertilization success was significantly reduced by EE2 in both sexes when mated with untreated fish of opposite sex. Progeny of fish treated with 1.2 ng/L EE2 showed increased anxiety in the novel tank test and increased light avoidance in the scototaxis test compared to control offspring.

    In conclusion, developmental exposure of zebrafish to low doses of EE2 resulted in persistent changes in behavior and fertility. The behavior of unexposed progeny was affected by their parents' exposure, which might suggest transgenerational effects.

  • 20.
    Volkova, Kristina
    et al.
    Södertörns Högskola.
    Reyhanian, Nasim
    Kot-Wasik, Agata
    Olsén, Håkan
    Porsch-Hällström, Inger
    Hallgren, Stefan
    Brain circuit imprints of developmental 17α-Ethinylestradiol exposure in guppies (Poecilia reticulata): persistent effects on anxiety but not on reproductive behaviour.2012In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 178, no 2, p. 282-90Article in journal (Refereed)
    Abstract [en]

    The effects of endocrine disruptors may vary with the timing of exposure. The physiological implications of adult exposure are present during and shortly after exposure while embryonic exposure can imprint changes manifested in adulthood. In this study, guppy (Poecilia reticulata) embryos were exposed to 2 and 20 ng/L of 17α-ethinylestradiol during development via the mother and reared in clean water from gestation until 6 months of age. As adults, fish exposed to 20 ng/L during development showed significantly altered behaviour in the Novel Tank test, where anxiety is determined as the tendency to remain at the bottom upon introduction into an unfamiliar tank. 17α-ethinylestradiol treatment increased the latency time before swimming to the upper half of the tank and decreased the number of transitions to the upper half. In control females the basal stress behaviour responses were significantly higher than in males, as indicated by longer latency period and fewer and shorter visits to the upper half, supporting the importance of gonadal hormones for the behaviour. The anxiety increased, however, with treatment in both sexes, suggesting that the observed response is not entirely due to feminisation of the males. Shoaling behaviour, analysed as tendency to leave a shoal of littermates, was neither sex-differentiated nor changed by treatment. Also male reproductive behaviour, brain aromatase activity and testes histology, previously shown to respond to oestrogen exposure in adult guppy, were unaffected by the developmental treatment. This suggests that the stress system in the guppy is very sensitive to 17α-ethinylestradiol, which possibly causes an early organisational imprint on the brain circuit that regulates stress reactions.

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