Evidence suggesting that di‐n‐butyl phthalate has antiandrogenic effects in fish

Abstract

Abstract-Phthalate ester plasticizers are anti-androgenic in mammals. High doses of certain phthalates consistently interfere with the normal development of male offspring exposed in utero, causing disrupted sperm production, abnormal development of the genitalia, and in some cases, infertility. In the environment, phthalates are considered ubiquitous, and are commonly measured in aquatic ecosystems at low ng to µg per litre concentrations. Given the similarity between mammalian and teleost endocrine systems, phthalate esters may be able to cause anti-androgenic endocrine disruption in fish in the wild. In the present study, adult male three-spined sticklebacks (Gasterosteus aculetaus) (n=8) were exposed to di-n-butyl phthalate (DBP) (0, 15, and 35 µg DBP/L) for 22 d and analyzed for changes in nesting behavior, plasma androgen concentrations, spiggin concentrations, and steroidogenic gene expression. Plasma testosterone concentrations were significantly higher in males from the 35 µg DBP/L group compared to the solvent 2 control, while plasma 11-ketotestosterone concentrations were not significantly affected.Expression of steroid acute regulatory protein and 3β-hydroxysteroid dehydrogenase remained unchanged. Spiggin concentrations were significantly lower in the males exposed to 35 µg DBP/L. Nest-building appeared to be slower in some males exposed to DBP, but this was not statistically significant. These results suggest that DBP has antiandrogenic effects in fish. However, further research is required to firmly establish the consequences of chronic DBP exposure in fish.

Accumulated HSV1-TK Proteins Interfere with Spermatogenesis through a Disruption of the Integrity of Sertoli-Germ Cell Junctions

“…Loss of testicular function is caused by various mechanisms such as antiandrogenic effects of phthalate esters in rats [10] and fish [11], disruption of microtubule dynamics by Sertoli cell toxicants [12][13][14][15][16], disruption of Ca 2+ homeostasis [17], disruption of the blood-testis barrier via the mitogen-activated protein kinase signaling pathway The affected genes were classified into 12 functional categories according to "Gene Ontology".…”

“…The present study demonstrated the disruption of all stages of spermatogenesis predicted by histopathological alterations in 3-month-old transgenic rats. These disorders were marked in terms of seminiferous epithelial sloughing, vacuolization and degeneration in spermatocytes in addition to abnormal elongated spermatids and spermatozoa in the seminiferous lumen.cDNA microarray and realtime PCR analyses revealed that the expression levels of four genes (cnot7, fgf7, testin and ostf1) significantly increased (P<0.05) and that those of two genes (versican and mamdc1) decreased (P<0.05).Loss of testicular function is caused by various mechanisms such as antiandrogenic effects of phthalate esters in rats [10] and fish [11], disruption of microtubule dynamics by Sertoli cell toxicants [12][13][14][15][16], disruption of Ca 2+ homeostasis [17], disruption of the blood-testis barrier via the mitogen-activated protein kinase signaling pathway In the epididymides of the transgenic rat, degenerating round spermatids (B1) and many types of abnormal elongated spermatids (B2-4) were frequently observed. Abnormal spermatozoa showing a breakage of surface membranes (B5) and decline in the member of outer dense fiber were also observed (B-6).…”

The impact of long term exposure to phthalic acid esters on reproduction in Chinese rare minnow (Gobiocypris rarus)

“…The significantly reduced plasma T and E 2 levels in females in this study may have been partly due to the inhibition of cyp17 and cyp19a gene expressions in the ovary. However, there are many inconsistent associations between sex hormone levels and transcriptions of genes involved in steroidogenesis both in vitro and in vivo assays (Aoki et al, 2011;Borch et al, 2006;Lambrot et al, 2009;Liu et al, 2005). Therefore, it has been suggested that the production of sex hormones is a complex process with multiple sensitive control points, and the genes involved in steroidogenesis are not transcribed to the same degree and correlations between hormone production and mRNA expression are not always observed (Gracia et al, 2007).…”

The effects on steroidogenesis and histopathology of adult male Japanese quails (Coturnix coturnix japonica) testis following pre-pubertal exposure to di(n-butyl) phthalate (DBP)

“…The control group was administered a corn-oil vehicle only (a dose of 1 mL/kg), while the other five experimental groups were administered intragastrically, daily using a dosage regimen of 1, 10, 50, 200, 400 mg DBP/kg/body mass (dissolved in corn oil), for a period of 30-days. In rats, the Non-Observable-Adverse-Effect-Level (NOAEL) of DBP by intra-gastric gavage was 50 mg/kg/day (Mylchreest et al, 2000;Zhang et al, 2004), while a dose of 0, 15, and 35 μg DBP/L (Aoki et al, 2011) and 0.1, 0.5, 1.0, 5.0 or 10 ppm DBP (Lee and Veeramachaneni, 2005) has been used in fish and amphibians, respectively. Overall, the doses used in the present avian study was chosen in order to achieve a dose-response relationship to DBP exposure on reproductive effects using relatively low experimental doses (1, 10 and 50 mg/kg body mass/day) and to high doses (200 and 400 mg/kg body mass/day), in order to obtain a mechanistic overview.…”