title: Acetamiprid inhibits testosterone synthesis by affecting the mitochondrial function and cytoplasmic adenosine triphosphate production in rat Leydig cells.
abstract: The insecticide acetamiprid is used to control noxious agricultural pests. However, it can cause mammalian toxicity. We evaluated the reproductive toxicity of acetamiprid in adult male Sprague Dawley rats. Rats were given oral acetamiprid alone or with vitamin E for 35 days. Rat plasma testosterone concentration and sperm quality decreased significantly as the levels of luteinizing hormone (LH) increased after exposure. At the same time, acetamiprid increased malondialdehyde and nitric oxide (NO) levels of Leydig cells. Further analysis showed that acetamiprid reduced the adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) production of Leydig cells, but the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) and the activity of adenylyl cyclase were not changed. Acetamiprid exposure also significantly diminished protein levels of steroidogenic acute regulatory protein (STAR), hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase cluster (HSD3B), and cytochrome P450, family 11, subfamily a, polypeptide 1 (CYP11A1), and testicular mRNA levels, which are cAMP-dependent proteins that are essential for steroidogenesis. Electron microscopy indicated mitochondrial membrane damage in the Leydig cells of the testes of exposed rats. Vitamin E ameliorated the impairment of acetamiprid on Leydig cells. Our results indicate that acetamiprid causes oxidative stress and mitochondrial damage in Leydig cells and inhibits the synthesis of testicular ATP and cAMP. Acetamiprid disrupts subsequent testosterone biosynthesis by decreasing the rate of conversion of cholesterol to testosterone and by preventing cholesterol from entering the mitochondria within the Leydig cells. These effects caused reproductive damage to the rats.
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Deying
authors.initials: D
authors.lastname: Kong
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Jidong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Laboratory Animal Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Shibin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Yuanshou
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Southwest University, Beibei, Chongqing, People's Republic of China.
authors.forename: Weirong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Delin
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Basic Medical Science, Zunyi Medical College, Zunyi Guizhou, People's Republic of China.
authors.forename: Renlian
authors.initials: R
authors.lastname: Cai
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D000242:Cyclic AMP / Q000378:metabolism; D007306:Insecticides / Q000097:blood / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008928:Mitochondria / Q000187:drug effects*; D000073943:Neonicotinoids / Q000097:blood / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010750:Phosphoproteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011974:Receptors, LH / Q000378:metabolism; D013081:Sperm Motility; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D007306:Insecticides; C000622692:LHCGR protein, rat; D000073943:Neonicotinoids; D010750:Phosphoproteins; D011974:Receptors, LH; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; C464485:acetamiprid; D000255:Adenosine Triphosphate; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases
keywords: Leydig cells; acetamiprid; inhibition; mitochondrial damage; testosterone synthesis