Androgenic profile and genotoxicity evaluation of testosterone propionate and novel synthesized heterocyclic steroids

ABSTRACT. 17-α-methyltestosterone (MT) is a synthetic hormone used in fish hatcheries to induce male monosex. Snails hold promise as possible test models to assess chemicals acting on the endocrine system. Biomphalaria glabrata is an aquatic gastropod mollusk (Pulmonata, Planorbidae) that can be easily maintained in aquaria, predisposing the species for use in ecotoxicological testing. This study evaluated the reproductive effects of MT on B. glabrata by examining histological changes and its reproductive performance. Ten snails per group were exposed for 4 weeks to different concentrations of MT (0.01, 0.1, and 1.0 mg/L). The total number of laid eggs, egg mass per group, size of type V oocytes, and production of spermatozoids were determined. Reproduction of B. glabrata was affected by MT. At the lowest concentration (0.01 mg/L), MT caused a statistically significant increase in the number of egg mass per snail compared with controls unexposed to MT. Histopathology analyses showed an increase in the sperm production at the higher MT concentrations of 0.1 and 1.0 mg/L. Chromatographic analyses of water samples showed that MT concentrations rapidly declined within a 96-h period. These results highlight the importance of giving more support to regulatory authorities, since MT is not registered for use on fish hatcheries in many countries around the world. Wastewater from fish farms discharged into aquatic ecosystems should be monitored for MT residues, since its presence could compromise the reproduction of other native snail species.

Section: Discussionmentioning

confidence: 99%

Effects of 17α-methyltestosterone on the reproduction of the freshwater snail Biomphalaria glabrata

Rivero-Wendt¹,

Borges²,

Oliveira-Filho³

et al. 2014

“…However, pyrimidinoandrostene, at both low and high doses, causes a significant increase in the mean value of chromosomal aberrations, showing that synthesized heterocyclic steroid androgens could be investigated for their possible genotoxic effects (Hana et al, 2008). The effects of MT on chromosomal synapsis in O. niloticus exposed orally at 50 mg/kg for 30 days have been also examined and MT did not significantly alter the pattern of the synaptonemal complex, or number and morphology of chromosomes (Carrasco et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Sex steroid hormones are considered non-genotoxic carcinogens, but controversial results have been reported regarding this subject (Hana et al, 2008). In a study using microarray technology to evaluate the effects of EDCs on Cyprinus carpio gene expression, it was observed that MT induced expression in a group of genes such as serum lectin, interleukin 2, and vitellogenin, which are associated with immune response, lipid transport, and oogenesis, respectively (Moens et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Lack of genotoxicity in Astyanax bimaculatus and Oreochromis niloticus of 17α-methyltestosterone used in fish hatcheries to produce male monosex populations

Rivero-Wendt

Miranda-Vilela²,

Ferreira³

et al. 2013

ABSTRACT. 17α-Methyltestosterone (MT) is widely used in fish hatcheries of many countries to produce male monosex populations. Its genotoxic risk to fish species is not well known and studies in other in vivo models are still inconclusive. MT was tested for genotoxicity in the fish species Oreochromis niloticus (tilapia), a target species, and Astyanax bimaculatus (lambari), a native non-target species. Genotoxicity was evaluated by the micronucleus test (MN), nuclear abnormalities (NA), and comet assay using peripheral erythrocytes of both species after a 96-h exposure to MT at concentrations of 0.01, 0.1, and 1.0 mg/L in the water. At the lowest exposure level of 0.01 These effects were not observed in the comet assay. Chromatographic analysis of water samples collected from aquariums at the beginning and end of each experiment showed that MT was consumed during the 96-h exposure. At the highest level of exposure (1.0 mg/L), 81.69% of the hormone was consumed during the exposure period. The chromatogram showed that at the lowest concentration level of 0.01 mg/L, 99.56% MT was consumed by the end of the exposure period. Thus, exposure to MT did not cause genotoxicity in either fish species.

“…These steroids possess potent anabolic or growth-promoting properties (Hana et al, 2008). Estrogenic/androgenic controls on reproduction/development in fish may differ substantially from those in higher vertebrates to the point that mammalian (rat) screening methods may not identify potential endocrine-disrupting chemicals (EDCs) in this important class of animals (Ankley et al, 2001).…”

Section: Histology Of Gonadsmentioning

confidence: 99%

“…This paucity of studies may be because sex steroids are recognized as non-genotoxic carcinogens. However, controversial results have been reported in this regard (Hana et al, 2008). Since the micronucleus test is a very sensitive and useful method that can detect both clastogenic and aneugenic activity (al-Sabti and Metcalfe, 1995), it is a good tool for monitoring this damage.…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic toxicity and gonadal effects of 17 α-methyltestosterone in Astyanax bimaculatus (Characidae) and Oreochromis niloticus (Cichlidae)

Rivero-Wendt

Miranda-Vilela²,

Ferreira³

et al. 2013

ABSTRACT. The synthetic hormone, 17-α-methyltestosterone (MT), is used in fish hatcheries to induce male monosex. Androgenic effects on various fish species have been reported; however, few studies have assessed possible genotoxic effects, although there are concerns about such effects in target and non-target species. We evaluated genotoxic and gonadal effects of MT in adult tilapia (Oreochromis niloticus) and Astyanax bimaculatus (a common native non-target fish in Brazil). Fish were fed for 28 days with ration containing MT (60 mg/L), a normal dose used in fish farming. Evaluation of MT genotoxicity was carried out through micronucleus test, nuclear abnormality, and comet assay analyses on peripheral erythrocyte cells collected by cardiac puncture. There were no significant differences in micronucleus frequencies and DNA damage in both species; however, MT caused cytogenetic toxicity in the non-target species, A. bimaculatus, with significantly increased erythrocyte nuclear abnormalities. Histopathological analyses of the female gonads of O. niloticus revealed that MT significantly inhibited the development of mature oocytes, while in A. bimaculatus it provoked Methyltestosterone's genotoxic and gonadal effects significant inhibition of spermatozoa production. We concluded that discharge of fish-hatcheries water onto the surface of aquatic ecosystems should be avoided due to risks to reproduction of native species.