title: Chronic exposure to perfluorododecanoic acid disrupts testicular steroidogenesis and the expression of related genes in male rats.
abstract: Perfluorododecanoic acid (PFDoA), a synthetic perfluorinated chemical, has been detected in environmental matrices, wildlife, and human serum. Its potential health risk for humans and animals has raised public concern. However, the effects of chronic PFDoA exposure on male reproduction remain unknown. The aim of this study was to determine the effects of chronic PFDoA exposure (110 days) on testosterone biosynthesis and the expression of genes related to steroidogenesis in male rats. In this study, we examined the serum levels of sex hormones, growth hormone, and insulin in male rats. Testicular morphology and the expression of key genes and proteins in testosterone biosynthesis were also analyzed. Markedly decreased serum testosterone levels were recorded after 110 days of PFDoA exposure at 0.2mg PFDoA/kg/day and 0.5mg PFDoA/kg/day, and cast-off cells were observed in some seminiferous tubules in testes exposed to 0.5mg PFDoA/kg/day. PFDoA exposure resulted in significantly decreased protein levels of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), along with significantly reduced mRNA levels of insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), and interleukin 1alpha (IL-1alpha) in rat testes at 0.2mg/kg/day and 0.5mg/kg/day. In addition, PFDoA exposure also affected the expression of some genes in the hypothalamo-neurohypophyseal system. However, PFDoA did not affect the expression of 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, or aromatase in testis and liver. These findings demonstrate that chronic PFDoA exposure disrupts testicular steroidogenesis and expression of related genes in male rats. Multiple factors may be involved in the inhibition of testosterone by PFDoA.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shi
authors.forename: Lina
authors.initials: L
authors.lastname: Ding
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.forename: Yixing
authors.initials: Y
authors.lastname: Feng
authors.forename: Muqi
authors.initials: M
authors.lastname: Xu
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005466:Fluorocarbons; D015870:Gene Expression / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000235:genetics; D007850:Lauric Acids / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D013997:Time Factors; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D004785:Environmental Pollutants; D005466:Fluorocarbons; D053582:Interleukin-1alpha; D007850:Lauric Acids; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017526:Receptor, IGF Type 1; C522391:perfluorododecanoic acid