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Persistent effects of developmental exposure to 17α-ethinylestradiol on the zebrafish (Danio rerio) brain transcriptome and stress behavior
Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Miljövetenskap.ORCID-id: 0000-0001-7239-7121
Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Biologi. Örebro University.
Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Biologi. Örebro university.
Uppsala university.
Vise andre og tillknytning
(engelsk)Manuskript (preprint) (Annet vitenskapelig)
HSV kategori
Identifikatorer
URN: urn:nbn:se:sh:diva-28425OAI: oai:DiVA.org:sh-28425DiVA, id: diva2:858126
Merknad

Som manuskript i avhandling. As manuscript in dissertation.

Tilgjengelig fra: 2015-09-30 Laget: 2015-10-01 Sist oppdatert: 2017-10-24bibliografisk kontrollert
Inngår i avhandling
1. Fishy behavior: persistent effects of early-life exposure to 17α-ethinylestradiol
Åpne denne publikasjonen i ny fane eller vindu >>Fishy behavior: persistent effects of early-life exposure to 17α-ethinylestradiol
2015 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Örebro: Örebro university, 2015. s. 62
Serie
Örebro Studies in Biology, ISSN 1650-8793 ; 9Södertörn doctoral dissertations, ISSN 1652-7399 ; 110
Emneord
Endocrine disruptors, anxiety, stress behavior, transgenerational effects, 17α-ethinylestradiol, developmental exposure, social behavior, fish
HSV kategori
Forskningsprogram
Biologi
Identifikatorer
urn:nbn:se:sh:diva-28426 (URN)978-91-7529-091-1 (ISBN)
Disputas
2015-10-05, Hörsalen, Musikhögskolan, Örebro, 13:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2015-10-01 Laget: 2015-10-01 Sist oppdatert: 2015-10-01bibliografisk kontrollert
2. Hitting the mark: Studies of alterations in behaviour and fertility in ethinyl estradiol-exposed zebrafish and search related biomarkers
Åpne denne publikasjonen i ny fane eller vindu >>Hitting the mark: Studies of alterations in behaviour and fertility in ethinyl estradiol-exposed zebrafish and search related biomarkers
2016 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

In this thesis, we have analysed the effects of EE2 on non-reproductive behaviours and fertility. We have showed that two doses of EE2 in male adult short-term exposures evokes opposite behaviours in the novel tank test. A lower dose induced increased bottom-dwelling, a sign of increased anxiety and a higher dose increased surface-dwelling, which would likely expose themselves to predation in a natural environment. Increased shoaling was observed in both exposures, possibly affecting feeding and reproduction opportunities. Fertility analysis of these fish demonstrated a complete inhibition of spawning in the highest dose group. To investigate mechanisms behind the spawning failure, we examined expression levels of genes involved in zebrafish sex differentiation and maintenance of gonadal function. We found downregulated transcription levels of male-predominant genes, suggesting a demasculinization of the testes contributing to functional sterility in these fish. We have demonstrated that non-reproductive behaviour in zebrafish is highly sensitive to EE2 exposure during development. After exposing male and female zebrafish to low doses of EE2 followed by remediation in clean water until adulthood, the fish displayed increased anxiety and shoaling behaviour, demonstrating persistent effects of EE2. Furthermore, behavioural effects were transferred to their progeny. Decreased fertilisation success of the developmentally exposed fish was observed in both sexes when mated to untreated animals of the opposite sex. These fertility effects persisted although the fish had a long remediation period, implying likely reduced fitness of fish populations in aquatic environments. Based on our findings on non-reproductive behaviours and fertility, we performed RNAsequencing analysis of the brain and testes in order to investigate possible biological mechanisms behind the persistent effects. There is a need for biomarkers allowing detection of both reversible and irreversible effects in animals exposed to estrogenic substances, hopefully contributing to better risk assessments for EDCs. Results from RNA-sequencing would serve as a basis for continued studies in pursuit of potential biomarkers.

sted, utgiver, år, opplag, sider
Örebro: Örebro university, 2016. s. 55
Serie
Örebro Studies in Biology, ISSN 1650-8793 ; 10Södertörn doctoral dissertations, ISSN 1652-7399 ; 115
Emneord
Endocrine disrupting compounds, 17α-ethinylestradiol, fertility, anxiety, behaviour, zebrafish, biomarkers, stress
HSV kategori
Identifikatorer
urn:nbn:se:sh:diva-29440 (URN)978-91-7529-115-4 (ISBN)
Disputas
2016-02-25, Sal MA636, Alfred Nobels allé 7, Huddinge, 13:00 (engelsk)
Opponent
Veileder
Forskningsfinansiär
The Foundation for Baltic and East European Studies
Tilgjengelig fra: 2016-02-04 Laget: 2016-02-04 Sist oppdatert: 2016-02-04bibliografisk kontrollert

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