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Title [en]
Endocrine disruption in fish: Effects on behaviour and reproduction, development af biomarkers and assessment of risk levels in the Baltic Sea
Abstract [en]
Endocrine disrupting chemicals (EDCs) interfere with the function of the hormone system of all vertebrates and several non-vertebrate species. A variety of EDCs are found in aquatic environments from industrial contamination and from wastewater, where urinary estrogens and synthetic estrogens used for birth control are important contributors. Evidence from field studies suggests relationship between environmental EDC exposure and reproductive alterations in fish, and feminisation of male fish living downstream of sewage treatment plants has been observed. Effects of estrogenic chemicals on reproductive variables, such as abnormal gonad structure and differentiation, intersexuality and sex reversal, decreased sperm count and expression of egg yolk protein in males are well established in many fish species. Studies in mammals and to some extent in fish have shown that EDC exposure during development affect not only fertility and reproduction, but also brain development and sexual and nonsexual behaviour. Changes induced in developing organisms seem to be largely irreversible. New experimental data, so far on rodents only, indicate that effects can be transmitted to offspring several generations later by epigenetic mechanisms, raising the possibility that EDCs can affect long-term fitness in wildlife and human. In the present project, we study if trans-generational effects of EDCs on reproduction and sexual and non-sexual behaviour can be identified in fish. We search for new biomarkers identifying inherited epigenetic changes, and will use them to monitor the Baltic marine ecosystem for signs of multigenerational insult by EDCs. Biomarkers detecting persistent effects of developmental exposure in wild populations will be important even if trans-generational effects are not observed. Furthermore, we have found that non-reproductive behaviour, affecting ecologically significant parameters such as anxiety and shoaling, are very sensitive to EDC exposure, and will further study the mechanism of interference with brain signalling. The main questions addressed are: - Can endocrine disrupting chemicals give reproduction disturbing trans-generational effects in fish? – Can biomarkers of persistent changes caused by exposure be identified, possibly connected to transgenerational effects that can be used to indicate reproduction disturbances in natural fish populations? - Are non-sexual behaviour and brain function important targets for EDCs in fish?
Publications (4 of 4) Show all publications
Porseryd, T., Larsson, J., Kellner, M., Bollner, T., Dinnétz, P. & Porsch Hällström, I. (2019). Altered non-reproductive behavior and feminization caused by developmental exposure to 17α-ethinylestradiol persist to adulthood in three-spined stickleback (Gasterosteus aculeatus). Aquatic Toxicology, 207, 142-152
Open this publication in new window or tab >>Altered non-reproductive behavior and feminization caused by developmental exposure to 17α-ethinylestradiol persist to adulthood in three-spined stickleback (Gasterosteus aculeatus)
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2019 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 207, p. 142-152Article in journal (Refereed) Published
Abstract [en]

The synthetic estrogen 17α-ethinylestradiol (EE2), ubiquitous in the aquatic environment and commonly detected in sewage effluents, interferes with the endocrine system in multiple ways. Exposure during sensitive windows of development causes persistent effects on fertility, reproductive and non-reproductive behavior in mammals and fish. In the present study, three-spined stickleback (Gasterosteus aculeatus) were exposed to nominal 0 and 20 ng/L EE2 from fertilization to 7 weeks post-hatch. After 8 months of remediation in clean water three non-reproductive behaviors, not previously analyzed in developmentally EE2-exposed progeny of wild-caught fish, were evaluated. Chemical analysis revealed that the nominal 0 and 20 ng/L exposure contained 5 and 30 ng/L EE2, respectively. Therefore, the use of control fish from previous experiments was necessary for comparisons. Fish exposed during development showed significant concentration-dependent reduction in anxiety-like behavior in the scototaxis (light/dark preference) test by means of shorter latency to first entrance to the white compartment, more visits in white, and longer total time in white compared to unexposed fish. In the novel tank test, developmental exposure significantly increased the number of transitions to the upper half of the aquaria. Exposure to EE2 during development did not alter shoal cohesion in the shoaling test compared with unexposed fish but fish exposed to 30 ng/L EE2 had significantly longer latency to leave the shoal and fewer transitions away from the shoal compared to fish exposed to 5 ng/L EE2. Skewed sex ratio with more females, sex reversal in genetic males as well as intersex in males was observed after exposure to 30, but not 5 ng/L EE2. In conclusion, EE2 exposure during development in three-spined stickleback resulted in persistent effects on anxiety-like behaviors. These long-term effects from developmental exposure are likely to be of higher relevance for natural populations than are short-term effects from adult exposure.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Endocrine disruption, 17α-ethinylestradiol, fish, estrogens, developmental exposure, behavior, intersex
National Category
Environmental Sciences
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-34932 (URN)10.1016/j.aquatox.2018.11.024 (DOI)000457659300016 ()30572174 (PubMedID)2-s2.0-85058462347 (Scopus ID)1556/42/2011 (Local ID)1556/42/2011 (Archive number)1556/42/2011 (OAI)
Funder
The Foundation for Baltic and East European Studies, A065-2011
Note

As manuscript in dissertation.

Available from: 2018-05-04 Created: 2018-05-04 Last updated: 2021-01-25Bibliographically approved
Porseryd, T., Reyhanian Caspillo, N., Volkova, K., Elabbas, L., Källman, T., Dinnétz, P., . . . Porsch Hällström, I. (2018). Testis transcriptome alterations in zebrafish (Danio rerio) with reduced fertility due to developmental exposure to 17α-ethinyl estradiol. General and Comparative Endocrinology, 262, 44-58
Open this publication in new window or tab >>Testis transcriptome alterations in zebrafish (Danio rerio) with reduced fertility due to developmental exposure to 17α-ethinyl estradiol
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2018 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 262, p. 44-58Article in journal (Refereed) Published
Abstract [en]

17α-Ethinylestradiol (EE2) is a ubiquitous aquatic contaminant shown to decrease fish fertility at low concentrations, especially in fish exposed during development. The mechanisms of the decreased fertility are not fully understood. In this study, we perform transcriptome analysis by RNA sequencing of testes from zebrafish with previously reported lowered fertility due to exposure to low concentrations of EE2during development. Fish were exposed to 1.2 and 1.6 ng/L (measured concentration; nominal concentrations 3 and 10 ng/L) of EE2 from fertilization to 80 days of age, followed by 82 days of remediation in clean water. RNA sequencing analysis revealed 249 and 16 genes to be differentially expressed after exposure to 1.2 and 1.6 ng/L, respectively; a larger inter-sample variation was noted in the latter. Expression of 11 genes were altered by both exposures and in the same direction. The coding sequences most affected could be categorized to the putative functions cell signalling, proteolysis, protein metabolic transport and lipid metabolic process. Several homeobox transcription factors involved in development and differentiation showed increased expression in response to EE2 and differential expression of genes related to cell death, differentiation and proliferation was observed. In addition, several genes related to steroid synthesis, testis development and function were differentially expressed. A number of genes associated with spermatogenesis in zebrafish and/or mouse were also found to be differentially expressed. Further, differences in non-coding sequences were observed, among them several differentially expressed miRNA that might contribute to testis gene regulation at post-transcriptional level. This study has generated insights of changes in gene expression that accompany fertility alterations in zebrafish males that persist after developmental exposure to environmental relevant concentrations of EE2 that persist followed by clean water to adulthood. Hopefully, this will generate hypotheses to test in search for mechanistic explanations.

Place, publisher, year, edition, pages
Academic Press, 2018
National Category
Other Biological Topics Environmental Sciences
Research subject
Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-29441 (URN)10.1016/j.ygcen.2018.03.011 (DOI)000430995100006 ()29526718 (PubMedID)2-s2.0-85044314644 (Scopus ID)1556/42/2011 (Local ID)1556/42/2011 (Archive number)1556/42/2011 (OAI)
Funder
The Foundation for Baltic and East European Studies, A065-2011Stockholm County Council, 806/3.1.1/2014
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2016-02-02 Created: 2016-02-04 Last updated: 2020-07-17Bibliographically approved
Porseryd, T., Volkova, K., Reyhanian Caspillo, N., Källman, T., Dinnétz, P. & Porsch Hällström, I. (2017). Persistent Effects of Developmental Exposure to 17α-Ethinylestradiol on the Zebrafish (Danio rerio) Brain Transcriptome and Behavior. Frontiers in Behavioral Neuroscience, 11, Article ID 69.
Open this publication in new window or tab >>Persistent Effects of Developmental Exposure to 17α-Ethinylestradiol on the Zebrafish (Danio rerio) Brain Transcriptome and Behavior
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2017 (English)In: Frontiers in Behavioral Neuroscience, ISSN 1662-5153, E-ISSN 1662-5153, Vol. 11, article id 69Article in journal (Refereed) Published
Abstract [en]

The synthetic estrogen 17α-ethinylestradiol (EE2) is an endocrine disrupting compound of concern due to its persistence and widespread presence in the aquatic environment. Effects of developmental exposure to low concentrations of EE2 in fish on reproduction and behavior not only persisted to adulthood, but have also been observed to be transmitted to several generations of unexposed progeny. To investigate the possible biological mechanisms of the persistent anxiogenic phenotype, we exposed zebrafish embryos for 80 days post fertilization to 0, 3 and 10 ng/L EE2 (measured concentrations 2.14 and 7.34 ng/L). After discontinued exposure, the animals were allowed to recover for 120 days in clean water. Adult males and females were later tested for changes in stress response and shoal cohesion, and whole-brain gene expression was analyzed with RNA sequencing. The results show increased anxiety in the novel tank and scototaxis tests, and increased shoal cohesion in fish exposed during development to EE2. RNA sequencing revealed 34 coding genes differentially expressed in male brains and 62 in female brains as a result of EE2 exposure. Several differences were observed between males and females in differential gene expression, with only one gene, sv2b, coding for a synaptic vesicle protein, that was affected by EE2 in both sexes. Functional analyses showed that in female brains, EE2 had significant effects on pathways connected to the circadian rhythm, cytoskeleton and motor proteins and synaptic proteins. A large number of non-coding sequences including 19 novel miRNAs were also differentially expressed in the female brain. The largest treatment effect in male brains was observed in pathways related to cholesterol biosynthesis and synaptic proteins. Circadian rhythm and cholesterol biosynthesis, previously implicated in anxiety behavior, might represent possible candidate pathways connecting the transcriptome changes to the alterations to behavior. Further the observed alteration in expression of genes involved in synaptogenesis and synaptic function may be important for the developmental modulations resulting in an anxiety phenotype. This study represents an initial survey of the fish brain transcriptome by RNA sequencing after long-term recovery from developmental exposure to an estrogenic compound.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2017
National Category
Biological Sciences
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-32462 (URN)10.3389/fnbeh.2017.00069 (DOI)000400103600001 ()28473760 (PubMedID)2-s2.0-85018300638 (Scopus ID)1556/42/2011 (Local ID)1556/42/2011 (Archive number)1556/42/2011 (OAI)
Funder
The Foundation for Baltic and East European Studies, A065-2011Stockholm County Council, 806/3.1.1/2014
Available from: 2017-05-03 Created: 2017-05-03 Last updated: 2020-07-17Bibliographically approved
Volkova, K., Caspillo, N. R., Porseryd, T., Hallgren, S., Dinnétz, P. & Porsch-Hällström, I. (2015). Developmental exposure of zebrafish (Danio rerio) to 17α-Ethinylestradiol affects non-reproductive behavior and fertility as adults, and increases anxiety in unexposed progeny. Hormones and Behavior, 73, 30-38
Open this publication in new window or tab >>Developmental exposure of zebrafish (Danio rerio) to 17α-Ethinylestradiol affects non-reproductive behavior and fertility as adults, and increases anxiety in unexposed progeny
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2015 (English)In: Hormones and Behavior, ISSN 0018-506X, E-ISSN 1095-6867, Vol. 73, p. 30-38Article in journal (Refereed) Published
Abstract [en]

Exposure to estrogenic endocrine disruptors (EDCs) during of 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 is 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 1.6ng/L EE2. After remediation for 82days non-reproductive behavior and fertilization success were analyzed in both sexes. Males and females from the 1.2ng/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 1.6ng/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 1.2ng/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 were affected by their parents' exposure, which might suggest transgenerational effects.

Place, publisher, year, edition, pages
Academic Press, 2015
Keywords
17α-Ethinylestradiol; Anxiety; Developmental exposure; Endocrine disruptors; F1 effects; Fertility; Neuroendocrinology; Social behavior; Stress behavior; Zebrafish
National Category
Biological Sciences Environmental Sciences
Research subject
Environmental Studies; Baltic and East European studies
Identifiers
urn:nbn:se:sh:diva-27795 (URN)10.1016/j.yhbeh.2015.05.014 (DOI)000360251800005 ()26072466 (PubMedID)2-s2.0-84934983120 (Scopus ID)1556/42/2011 (Local ID)1556/42/2011 (Archive number)1556/42/2011 (OAI)
Funder
The Foundation for Baltic and East European Studies, A037-2008The Foundation for Baltic and East European Studies, A065-2011
Available from: 2015-06-18 Created: 2015-06-18 Last updated: 2020-07-17Bibliographically approved
Principal InvestigatorPorsch Hällström, Inger
Co-InvestigatorGrahn, Mats
Co-InvestigatorOlsén, Håkan
Co-InvestigatorBollner, Tomas
Co-InvestigatorReyhanian, Nasim
Co-InvestigatorVolkova, Kristina
Coordinating organisation
Södertörn University
Funder
Period
2012-01-01 - 2014-12-31
Keywords [sv]
Östersjö- och Östeuropaforskning
Keywords [en]
Baltic and East European studies
National Category
Biochemistry and Molecular BiologyZoologyEcology
Identifiers
DiVA, id: project:1739Project, id: A065-2011_OSS

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