Low dose of fire retardant, 2,2’,4,4’-tetrabromodiphenyl ether (BDE47), stimulates the proliferation and differentiation of progenitor Leydig cells of male rats during prepuberty

Autor: Yiyan Wang, Huitao Li, Ren-Shan Ge, Yingfen Ying, Zengqiang Li, Changchang Li, Haoni Yan, Qiqi Zhu, Xiaoheng Li
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
endocrine system
medicine.medical_specialty
medicine.drug_class
Toxicology
CREB
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Proliferating Cell Nuclear Antigen
Internal medicine
Prepuberty
11-beta-Hydroxysteroid Dehydrogenase Type 1
Halogenated Diphenyl Ethers
medicine
Animals
Increased serum testosterone level
Cholesterol Side-Chain Cleavage Enzyme
Sexual Maturation
Cells
Cultured
Dose-Response Relationship
Drug
Molecular Structure
biology
Leydig cell
Chemistry
Stem Cells
Leydig Cells
SOX9 Transcription Factor
General Medicine
Luteinizing Hormone
Androgen
Rats
Proliferating cell nuclear antigen
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
biology.protein
Follicle Stimulating Hormone
Luteinizing hormone
030217 neurology & neurosurgery
Corn oil
Zdroj: Toxicology Letters. 342:6-19
ISSN: 0378-4274
Popis: 2,2',4,4'-Tetrabromodiphenyl ether (BDE47), a flame retardant, is extensively distributed in the food chain. However, whether BDE47 affects Leydig cell development during prepuberty remains unclear. BDE47 was daily gavaged to 21-day-old Sprague-Dawley male rats with 0 (corn oil), 0.1, 0.2, and 0.4 mg/kg for 14 days. BDE47 did not affect the body weight or testis weight of rats. It significantly increased serum testosterone level at 0.4 mg/kg, but decreased luteinizing hormone (LH) level without affecting estradiol level. BDE47 induced Leydig cell hyperplasia (the number of CYP11A1-positive Leydig cells increased), and up-regulated the expression of Scarb1, Star, Hsd11b1, Pcna, and Ccnd1 in the testis. BDE47 significantly reduced p53 and p21 levels but increased CCND1 level. It also markedly increased the phosphorylation of AKT1, AKT2, ERK1/2, and CREB. BDE47 significantly up-regulated the expression of Scarb1, Star, and Hsd11b1 and stimulated androgen production by immature Leydig cells from rats under basal, LH, and 8Br-cAMP stimulated conditions at 100 nM in vitro. In conclusion, BDE47 increased Leydig cell number and up-regulated the expression of Scarb1 and Star, thereby leading to increased testosterone synthesis.
Databáze: OpenAIRE
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