title: Effect of polybrominated diphenyl ether (BDE-209) on testicular steroidogenesis and spermatogenesis through altered thyroid status in adult mice.
abstract: Polybrominated diphenyl ethers (PBDEs), a class of brominated flame retardants (BFRs), have been widely used in many products to minimize the risk of fire, mainly by mixing in polymer products. BDE-209, a congener of PBDEs having structural similarity with thyroid hormones, acts as an endocrine disruptor by interfering with thyroid homeostasis. However, little is known about the effect of BDE-209 exposure on testicular steroidogenesis and spermatogenesis. This study was therefore conducted in adult mice to examine the effect of BDE-209 on testicular steroidogenesis and spermatogenesis in relation to thyroid status, and to explore possible mechanism(s) of its action. Adult Parkes strain male mice were orally gavaged with 750 and 950mg/kg BW of BDE-209 in corn oil for 35days. Significant reductions were noted in the levels of serum total T3,T4and testosterone in mice treated with 950mg/kg BW of BDE-209 compared to controls; histologically, testes showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; further, number and viability of spermatozoa were also adversely affected in cauda epididymidis of these mice. Semiquantitative RT-PCR and western blot analyses also showed significant reductions in both testicular mRNA and protein levels of steroidogenic factor 1 (SF-1), steroidogenic acute regulatory (StAR) protein, cytochrome P450scc (CYP11A1), 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD) in 950mg dose treated-mice compared to controls. Immunohistochemical and immunoblot analyses further revealed a marked decrease in proliferating cell nuclear antigen (PCNA) positive cells in testes of 950mg dose of BDE-209-treated mice. However, 750mg dose of BDE-209 had no effect on the above parameters. In conclusion, our results suggest that exposure of BDE-209 to adult mice causes reduction in serum levels of thyroid hormones and altered thyroid status may partly result into impairment of testicular steroidogenesis because of down-regulated expression of SF-1, thereby causing suppression of spermatogenesis.
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Debarshi
authors.initials: D
authors.lastname: Sarkar
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Jayita Pal
authors.initials: JP
authors.lastname: Chowdhury
authors.affiliation: Department of Zoology, Banaras Hindu University, Varanasi 221005, India. Electronic address: shioks@rediffmail.com.
authors.forename: Shio Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D005411:Flame Retardants / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D055768:Halogenated Diphenyl Ethers / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012671:Seminiferous Tubules / Q000187:drug effects / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000097:blood; D013959:Thyroid Diseases / Q000139:chemically induced* / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; D005411:Flame Retardants; D012739:Gonadal Steroid Hormones; D055768:Halogenated Diphenyl Ethers; D013963:Thyroid Hormones; D013739:Testosterone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D002786:Cholesterol Side-Chain Cleavage Enzyme; C010902:decabromobiphenyl ether
keywords: BDE-209; Mice; Spermatogenesis; Testis; Testosterone; Thyroid hormones