Effects of short-term exposure to the model anti-androgen, flutamide on reproductive function based endpoints in female Murray rainbowfish (Melanotaenia fluviatilis)

Bhatia, Harpreet; Kumar, Anu; Chapman, John C.; McLaughlin, Michael J.

doi:10.1016/j.ecoenv.2014.07.027

Cited by 11 publications

(5 citation statements)

References 72 publications

(94 reference statements)

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“…In fish, flutamide adversely affects male and female sex differentiation. In females it causes hastened ovarian development with distorted morphology ( Chakrabarty et al, 2012 ), a reduction of relative gonads size ( Milsk et al, 2016 ) and disturbs female reproduction ( Bhatia et al, 2014b ). In males, flutamide affects secondary sex characteristics ( Milsk et al, 2016 ) and testicular growth ( Bhatia & Kumar, 2016 ; Bhatia et al, 2014a ; Yin et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…An important class of antiandrogens are synthetic drugs such as CPA and flutamide that were specifically designed to competitively bind to androgen receptors (AR) in vivo ( Bhatia et al, 2014b ). These AR antagonists have been used to treat androgen-dependent prostate cancer in men and menstrual cycle irregularities in women with polycystic ovarian syndrome ( Heinlein & Chang, 2004 ; Paradisi et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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No effects of the antiandrogens cyproterone acetate (CPA), flutamide and p,p’-DDE on early sexual differentiation but CPA-induced retardation of embryonic development in the domestic fowl (Gallus gallus domesticus)

Jessl,

Oehlmann

2023

PeerJ

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Because a wide range of environmental contaminants are known to cause endocrine disorders in humans and animals, in vivo tests are needed to identify such endocrine disrupting chemicals (EDCs) and to assess their biological effects. Despite the lack of a standardized guideline, the avian embryo has been shown to be a promising model system which responds sensitively to EDCs. After previous studies on the effects of estrogenic, antiestrogenic and androgenic substances, the present work focuses on the effects of in ovo exposure to p,p’-DDE, flutamide and cyproterone acetate (CPA) as antiandrogenic model compounds regarding gonadal sex differentiation and embryonic development of the domestic fowl (Gallus gallus domesticus). The substances were injected into the yolk of fertilized eggs on embryonic day one. On embryonic day 19 sex genotype and phenotype were determined, followed by gross morphological and histological examination of the gonads. Treatment with flutamide (0.5, 5, 50 µg/g egg), p,p’-DDE (0.5, 5, 50 µg/g egg) or CPA (0.2, 2, 20 µg/g egg) did not affect male or female gonad development, assessed by gonad surface area and cortex thickness in both sexes and by the percentage of seminiferous tubules in males as endpoints. This leads to the conclusion that antiandrogens do not affect sexual differentiation during embryonic development of G. gallus domesticus, reflecting that gonads are not target organs for androgens in birds. In ovo exposure to 2 and 20 µg CPA/g egg, however, resulted in significantly smaller embryos as displayed by shortened lengths of skull, ulna and tarsometatarsus. Although gonadal endpoints were not affected by antiandrogens, the embryo of G. gallus domesticus is shown to be a suitable test system for the identification of substance-related mortality and developmental delays.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

No effects of the antiandrogens cyproterone acetate (CPA), flutamide and p,p’-DDE on early sexual differentiation but CPA-induced retardation of embryonic development in the domestic fowl (Gallus gallus domesticus)

Jessl,

Oehlmann

2023

PeerJ

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“…To evaluate the adverse effects of a drug, multiple endpoints could be selected. The included studies covered endpoints from conventional tests: mortality, inhibition of mobility/growth and reproduction, to more advanced endpoints such as genotoxicity (DNA damage), neurotoxicity (AChE activity), oxidative stress (by testing biomarkers such as SOD, CAT, T-and SE-GPx, GST and lipid peroxidation), physical abnormalities (body weight and length, embryonic deformities), physiological effects (heart rate, fecundity and fertility), behaviour (locomotion, swimming performance, feeding, burrowing activity), in addition to the expression of several genes related to gonads and brain development, and histological studies; among others (Bhatia et al, 2014;Trombini et al, 2016;Yan et al, 2017).…”

Section: Choice Of Suitable Endpoints 21mentioning

confidence: 99%

Aquatic ecotoxicology of anticancer drugs: A systematic review

Nassour

Nabhani‐Gebara

Barton

et al. 2021

Science of The Total Environment

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“…The concentrations of sex steroid hormones, E2 and 11-keto testosterone (11-KT) in the whole-body homogenates, were measured using enzyme immunoassay (EIA) kits (Cayman Chemicals, USA) Bhatia et al (2014c). The method was validated by investigating parallelism between E2 or 11-KT standards and the hormone concentrations in serially diluted (1:2-1:256) whole-body homogenates of fish.…”

Section: Hormone Analysesmentioning

confidence: 99%

Long‐term exposures to di‐n‐butyl phthalate inhibit body growth and impair gonad development in juvenile Murray rainbowfish (Melanotaenia fluviatilis)

Bhatia

Kumar

Chapman³

et al. 2014

J of Applied Toxicology

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The aim of the present study was to evaluate whether long-term exposures to environmentally relevant concentrations of di-n-butyl phthalate (DnBP) disrupt the reproduction-based endpoints in juvenile Murray rainbowfish (Melanotaenia fluviatilis). Fish were exposed to 5, 15 or 50 µg l(-1) DnBP for 30, 60 and 90 days each, and the effects on survival, body growth, whole-body concentrations of sex steroid hormones and gonadal development were investigated. The lowest observed effective concentration to affect the condition factor after 90 days was 5 µg l(-1). Complete feminization of the gonad was noted in fish exposed to 5 µg l(-1) for 90 days and to 15 and 50 µg l(-1) of DnBP for 30 or 60 days. After 90 days of exposure to DnBP, the ovaries were regressed and immature as opposed to the control fish which were in early-vitellogenic stage. Testes, present only in fish exposed to 5 µg l(-1) of DnBP for 30 or 60 days, were immature in comparison to the control fish that contained testes in the mid-spermatogenic phase. The E2/11-KT ratio was significantly higher only after exposures to 5 µg l(-1) DnBP for 90 days and 50 µg l(-1) DnBP for 30 days. Our data suggest that exposures to 5 µg l(-1) DnBP for 30 days did not have profound effects on body growth and gonadal differentiation of fish. However, 30 days of exposure to 15 µg l(-1) could interfere with the gonad development and to 50 µg l(-1) could compromise the hormonal profile of juvenile fish.

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Effects of short-term exposure to the model anti-androgen, flutamide on reproductive function based endpoints in female Murray rainbowfish (Melanotaenia fluviatilis)

Cited by 11 publications

References 72 publications

No effects of the antiandrogens cyproterone acetate (CPA), flutamide and p,p’-DDE on early sexual differentiation but CPA-induced retardation of embryonic development in the domestic fowl (Gallus gallus domesticus)

No effects of the antiandrogens cyproterone acetate (CPA), flutamide and p,p’-DDE on early sexual differentiation but CPA-induced retardation of embryonic development in the domestic fowl (Gallus gallus domesticus)

Aquatic ecotoxicology of anticancer drugs: A systematic review

Long‐term exposures to di‐n‐butyl phthalate inhibit body growth and impair gonad development in juvenile Murray rainbowfish (Melanotaenia fluviatilis)

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