%0 Generic
%A Faßbender, Christopher
%D 2013
%F heidok:15112
%R 10.11588/heidok.00015112
%T Genotoxicity and effects on fertility, reproduction, development as well as histology in zebrafish (Danio rerio) in a multi-generation study – is there a relationship?
%U https://archiv.ub.uni-heidelberg.de/volltextserver/15112/
%X To date, it is unclear whether adverse effects by genotoxic anthropogenic pollutants in the aquatic  environment are linked to the decline of fish populations observed in European and North American  freshwaters. Therefore, there is a need for investigations into the relationship between genotoxic stress  and detrimental effects on development and reproduction in fish. In order to contribute to this field, the  present thesis investigates effects of the alkylating genotoxin methyl methanesulfonate (MMS) on  genetic integrity, histological status and reproduction in zebrafish (Danio rerio). In addition, in their  unexposed offspring (F1), larval development, histological status and reproduction as well as development  in the F2 generation were examined at the population level in order to identify potential inheritable  effects of genotoxicity.  First, methods for the use of primary gonad cells from zebrafish in the alkaline comet assay and histological  sections of testis and ovary in the micronucleus test were developed. After in vivo exposure of  adult zebrafish to MMS for up to two weeks, in the comet assay, concentrations-dependent genotoxic  effects were detected in gonads, liver and gills. Likewise, the micronucleus frequency was elevated by  MMS in all of these organs. Thus, the concentration range adequate for MMS exposure in the designated  multi-generation experiment was identified. In the next step, zebrafish (F0) were exposed to  MMS in vivo from fertilization until the age of one year. Mortality of F0 fish clearly depended on  MMS concentrations. In exposed fish, times of first spawning were delayed and fertility was reduced.  However, no unequivocal effects on growth were found. In F1 fish derived from MMS-exposed fish,  teratogenic effects were increased, larval survival was reduced and sex ratio was shifted towards females.  However, compared to the exposed F0 generation, fertility of the non-exposed F1 generation  recovered. Development and survival rates recovered in the F2 generation. Significant genotoxic effects  were found in the livers, gills and gonads of either sex of the F0 generation. Regarding histopathological  aberrations and external lesions, mainly malformations of eyes, gills and liver and a number  of neoplasia were observed in both the F0 and F1 generation. According to indirect measurement of  MMS concentrations using ion chromatography, real concentrations in the replicate tanks were similar.  Taken together, chronic exposure of zebrafish to MMS led to DNA damage in somatic and generative  tissues, induced the formation of a multitude of histopathological aberrations and affected survival,  reproduction and development in exposed fish and their offspring. Regarding several endpoints, cessation  of exposure allowed for recover over the generations. Combining these results with data of previous  studies and transferring them to the environmental situation, there is considerable evidence that  anthropogenic genotoxicants play a role in the decline of wild fish populations.
%Z Chapter II of the thesis is based on the following publication:  Faßbender, C., Braunbeck, T. (2013): Assessment of genotoxicity in gonads, liver and gills of  zebrafish (Danio rerio) by use of the comet assay and micronucleus test after in vivo exposure  to methyl methanesulfonate. Bull Environ Contam Toxicol, DOI 10.1007/s00128-013-1007-6    Chapter III and parts of chapter IV are based on the following publication:  Faßbender, C., Braunbeck, T., Reproductive and genotoxic effects in zebrafish after chronic  exposure to methyl methanesulfonate in a multigeneration study. Ecotoxicology, DOI  10.1007/s10646-013-1057-x    The final publications of these articles are available at http://link.springer.com