Endosulfan and flutamide impair testicular development in the juvenile Asian catfish, Clarias batrachus

• Published in: Aquatic toxicology 2012-04, Vol.110-111, p.123-132
• Main Authors: Rajakumar, A., Singh, R., Chakrabarty, S., Murugananthkumar, R., Laldinsangi, C., Prathibha, Y., Sudhakumari, C.C., Dutta-Gupta, A., Senthilkumaran, B.
• Format: Article
• Language: English
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism; 11-Ketotestosterone; Agnatha. Pisces; Animal, plant and microbial ecology; Animals; antagonists; Antineoplastic Agents, Hormonal - toxicity; Applied ecology; bioaccumulation; Biological and medical sciences; brain; Catfish; Catfishes - growth & development; Catfishes - metabolism; Clarias batrachus; drugs; Ecotoxicology, biological effects of pollution; Endocrine Disruptors - toxicity; endocrine-disrupting chemicals; Endosulfan; Endosulfan - toxicity; enzyme immunoassays; enzymes; Flutamide; Flutamide - toxicity; Fundamental and applied biological sciences. Psychology; General aspects; genes; germ; gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - metabolism; histology; Insecticides - toxicity; Male; males; neurotoxicity; prostatic neoplasms; quantitative polymerase chain reaction; receptors; risk; sediments; sexual development; spermatocytes; Spermatocytes - drug effects; spermatogonia; Spermatogonia - drug effects; steroidogenesis; steroids; surface water; testes; Testicular development; Testis - drug effects; Testis - growth & development; Testis - metabolism; Testosterone; Testosterone - metabolism; transcription factors; Vertebrates: general zoology, morphology, phylogeny, systematics, cytogenetics, geographical distribution; Water Pollutants, Chemical - toxicity
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2011.12.018

► Endosulfan and/or flutamide retard(s) testicular differentiation in juvenile fish. ► Endosulfan and/or flutamide target(s) cfGnRH-Tph2 axis, either directly or indirectly. ► Effects of endosulfan and/or flutamide on plasma androgen levels. ► Compared changes in testis-related transcripts with testis germ cell distribution. ► Our study on endosulfan endorse its prompt and complete phase-out/ban. Endosulfan and flutamide, a widely used pesticide and a prostate cancer/infertility drug, respectively, have an increased risk of causing endocrine disruption if they reach water bodies. Though many studies are available on neurotoxicity/bioaccumulation of endosulfan and receptor antagonism of flutamide, only little is known about their impact on testicular steroidogenesis at molecular level. Sex steroids play an important role in sex differentiation of lower vertebrates including fishes. Hence, a small change in their levels caused by endocrine disruptors affects the gonadal development of aquatic vertebrates significantly. The aim of this study was to evaluate the effects of endosulfan and flutamide on testis-related transcription factor and steroidogenic enzyme genes with a comparison on the levels of androgens during critical period of catfish testicular development. We also analyzed the correlation between the above-mentioned genes and catfish gonadotropin-releasing hormone (cfGnRH)-tryptophan hydroxylase2 (tph2). The Asian catfish, Clarias batrachus males at 50 days post hatch (dph) were exposed to very low dose of endosulfan (2.5μg/L) and flutamide (33μg/L), alone and in combination for 50 days. The doses used in this study were far less than those used in the previous studies of flutamide and reported levels of endosulfan in surface water and sediments. Sampling was done at end of the treatments (100dph) to perform testicular germ cell count (histology), measurements of testosterone (T) and 11-ketotestosterone (11-KT) by enzyme immunoassay and transcript quantification by quantitative real-time PCR. In general, treatments decreased the expression of several genes including testis-related transcription factors (dmrt1, sox9a and wt1), steroidogenic enzymes (11β-hsd2, 17β-hsd12 and P450c17), steroidogenic acute regulatory protein and orphan nuclear receptors (nr2c1 and Ad4BP/SF-1). In contrast, the transcripts of cfGnRH and tph2 were elevated in the brain of all treated groups with maximum elevation in the endosulfan group. However, combination of endosulfan