Alterations in gene expression and testosterone synthesis in the testes of male rats exposed to perfluorododecanoic acid.
Perfluorododecanoic acid (PFDoA, C12), a synthetic perfluorinated chemical containing 12 carbons, has broad industrial applications and has been detected in sera from humans and other animals; however, few reports have addressed the effects of PFDoA exposure on male reproduction. In the present study, the effects of PFDoA exposure on testes ultrastructure, testosterone levels, and steroidogenic gene expression were investigated. Male rats were orally dosed for 14 days with 1, 5, or 10 mg PFDoA/kg/day or with vehicle. Absolute testis weight was diminished at the highest dose while relative testes weight was markedly increased at doses of 5 and 10 mg/kg/day. Total serum cholesterol levels were significantly increased at the highest dose. While luteinizing hormone was significantly decreased at the highest dose, testosterone was markedly decreased at doses of 5 and 10 mg PFDoA/kg/day. Serum levels of follicle-stimulating hormone were not significantly affected by PFDoA, and estradiol levels were markedly decreased only at 5 mg/kg/day. Leydig cells, Sertoli cells, and spermatogenic cells from rats that received 5 or 10 mg PFDoA/kg/day, exhibited apoptotic features including dense irregular nuclei, condensed chromatin, ill-defined nuclear membranes, and abnormal mitochondria. PFDoA exposure resulted in significant declines in mRNA expression of several genes involved in cholesterol transport and steroid biosynthesis at doses of 5 and 10 mg PFDoA/kg/day, while the gene expression of luteinizing hormone receptor and aromatase was not significantly changed. Our results demonstrate that PFDoA affects the reproduction function of male rats via alterations in steroidogenesis genes, testosterone levels, and testes ultrastructure.
Shi
Zhimin
Z
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China.
Zhang
Hongxia
H
Liu
Yang
Y
Xu
Muqi
M
Dai
Jiayin
J
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005466:Fluorocarbons; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression / Q000187:drug effects*; D007850:Lauric Acids / Q000633:toxicity; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011974:Receptors, LH / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis / Q000235:genetics; D013737:Testis / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood
D018955:CD36 Antigens; D005466:Fluorocarbons; D007850:Lauric Acids; D012333:RNA, Messenger; D011974:Receptors, LH; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; C522391:perfluorododecanoic acid