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Fishy behavior: persistent effects of early-life exposure to 17α-ethinylestradiol
Södertörn University, School of Natural Sciences, Technology and Environmental Studies, Biology. Örebro University.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The synthetic estrogen 17α-ethinylestradiol (EE2) is an endocrine disrupting chemical (EDC) of concern due to its persistent nature and widespread presence in the aquatic environment. In mammals, effects of developmental EDC exposure on reproduction and behavior not only persist to adulthood after discontinued exposure, but are also inherited by several consecutive unexposed generations. The results presented in this thesis demonstrate that non-reproductive behavior in fish is highly sensitive to the influence of EE2 during development and the effects do not appear to be restored after a long recovery period in clean water. We have shown that exposure to low doses of EE2 during development results in increased anxiety in two fish species (zebrafish and guppy) and their offspring. We have also demonstrated that the effects of EE2 on anxiety are apparent in both sexes and are transgenerationally transmitted to two consecutive generations of unexposed offspring in the guppy. In order to investigate the possible biological mechanisms of the observed persistent effects on non-reproductive behavior, we also performed an RNA sequencing analysis of the whole-brain transcriptome in developmentally exposed zebrafish after remediation in clean water until adulthood. Differential expression of 33 genes in males and 62 genes in females were observed as a result of EE2 exposure, with only one gene affected in both sexes. Functional analysis revealed cholesterol biosynthesis and circadian rhythm to be the top two affected pathways in males and females, respectively. Both pathways have previously been implicated in anxiety behavior and represent possible candidates connecting the transcriptome alterations to the observed behavioral phenotype. The study represents an initial survey of the fish brain transcriptome by means of RNA sequencing after long-term recovery from developmental exposure to an estrogenic compound.

Place, publisher, year, edition, pages
Örebro: Örebro university , 2015. , p. 62
Series
Örebro Studies in Biology, ISSN 1650-8793 ; 9Södertörn doctoral dissertations, ISSN 1652-7399 ; 110
Keywords [en]
Endocrine disruptors, anxiety, stress behavior, transgenerational effects, 17α-ethinylestradiol, developmental exposure, social behavior, fish
National Category
Biological Sciences
Research subject
Biology
Identifiers
URN: urn:nbn:se:sh:diva-28426ISBN: 978-91-7529-091-1 (print)OAI: oai:DiVA.org:sh-28426DiVA, id: diva2:858133
Public defence
2015-10-05, Hörsalen, Musikhögskolan, Örebro, 13:00 (English)
Opponent
Supervisors
Available from: 2015-10-01 Created: 2015-10-01 Last updated: 2015-10-01Bibliographically approved
List of papers
1. Brain circuit imprints of developmental 17α-ethinylestradiol exposure in guppies (Poecilia reticulata): Persistent effects on anxiety but not on reproductive behaviour
Open this publication in new window or tab >>Brain circuit imprints of developmental 17α-ethinylestradiol exposure in guppies (Poecilia reticulata): Persistent effects on anxiety but not on reproductive behaviour
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2012 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 178, no 2, p. 282-290Article in journal (Refereed) Published
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 ng/L 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 20ng/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 feminization of the males. Shoaling behaviour, analyzed 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.

Place, publisher, year, edition, pages
Academic Press, 2012
Keywords
Endocrine disruption, Xenoestrogens, Sexual dimorphism, Anxiety, Stress behaviour, gonad histology, embryonic exposure
National Category
Biochemistry and Molecular Biology Environmental Sciences
Research subject
Environmental Studies
Identifiers
urn:nbn:se:sh:diva-16353 (URN)10.1016/j.ygcen.2012.05.010 (DOI)000307694100013 ()2-s2.0-84863217808 (Scopus ID)
Funder
The Foundation for Baltic and East European Studies
Available from: 2012-06-07 Created: 2012-06-07 Last updated: 2020-03-31Bibliographically approved
2. Transgenerational effects of 17α-Ethinyl Estradiol on anxiety behavior in the guppy, Poecilia reticulata
Open this publication in new window or tab >>Transgenerational effects of 17α-Ethinyl Estradiol on anxiety behavior in the guppy, Poecilia reticulata
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2015 (English)In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 223, p. 66-72Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Academic Press, 2015
National Category
Zoology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-28427 (URN)10.1016/j.ygcen.2015.09.027 (DOI)000366438300008 ()26431611 (PubMedID)2-s2.0-84944226825 (Scopus ID)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2015-09-30 Created: 2015-10-01 Last updated: 2020-03-31Bibliographically approved
3. Developmental exposure of zebrafish (Danio rerio) to 17α-Ethinylestradiol affects non-reproductive behavior and fertility as adults, and increases anxiety in unexposed progeny
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
4. Persistent effects of developmental exposure to 17α-ethinylestradiol on the zebrafish (Danio rerio) brain transcriptome and stress behavior
Open this publication in new window or tab >>Persistent effects of developmental exposure to 17α-ethinylestradiol on the zebrafish (Danio rerio) brain transcriptome and stress behavior
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Zoology Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:sh:diva-28425 (URN)
Note

Som manuskript i avhandling. As manuscript in dissertation.

Available from: 2015-09-30 Created: 2015-10-01 Last updated: 2017-10-24Bibliographically approved

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Volkova, Kristina

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