The pyrethroid insecticides permethrin and esfenvalerate do not disrupt testicular steroidogenesis in the rat fetus. (1st December 2018)

• Record Type: Journal Article
• Authors: Saillenfait, Anne-Marie; Sabaté, Jean-Philippe; Denis, Flavien; Antoine, Guillaume; Robert, Alain; Eljarrat, Ethel
• Is Part Of: Toxicology. Volume 410(2018)
• Page Start: 116
• Page End: 124
• Publication Date: 2018-12-01
• Subjects: 3βHSD 3β-hydroxysteroid dehydrogenase -- 17βHSD 17β-hydroxysteroid dehydrogenase -- cDNA complementary DNA -- DBP dibutyl phthalate -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- GD Gestation day -- HMG-CoA reductase 3-hydroxy-3-methylglutaryl coenzyme A reductase -- HMG-CoA synthase 3-hydroxy-3-methylglutaryl-coenzyme A synthase -- mRNA messenger RNA -- NOAEL no-observed-adverse-effect level -- 3-PBA 3-phenoxybenzoic acid -- P450 17A1 cytochrome P450 17A1 -- P450scc cytochrome P450 cholesterol side-chain-cleavage enzyme -- PVC polyvinyl chloride -- RfD Reference dose -- SR-B1 scavenger receptor class B type 1 -- SD standard deviation -- StAR steroid acute regulatory protein; Permethrin -- Esfenvalerate -- Rat -- Pyrethroids -- Male reproductive development -- Testosterone -- Steroidogenesis -- Testis -- Fetus; Toxicology -- Periodicals; Chemicals -- Physiological effect -- Periodicals; 615.9005
• DOI: 10.1016/j.tox.2018.09.007
• Languages: English
• ISSNs: 0300-483X

Abstract

Highlights: The insecticides permethrin or esfenvalerate were administered to pregnant rats. They had no effects on the fetal rat testis up to maternal toxic doses. mRNA levels of testicular testosterone biosynthetic enzymes were not impaired. Ex vivo fetal testicular testosterone production was not affected. Levels of their metabolite, 3-PBA, in the amniotic fluid increased with the dose. Abstract: The present study investigated the effects of maternal exposure to the widely used pyrethroid insecticides, permethrin and esfenvalerate, on fetal testicular steroidogenesis. Pregnant Sprague-Dawley rats were administered permethrin at doses of 1, 10, 50, or 100 mg/kg/day, or esfenvalerate at 0.1, 1, 7.5 or 15 mg/kg/day, by gavage, from gestation day (GD) 13 to 19. Testicular testosterone production and the expression of several key genes necessary for cholesterol and androgen synthesis and transport were assessed in GD 19 male fetuses. Dams treated with 100 mg/kg/day of permethrin or 15 mg/kg/day of esfenvalerate showed clinical signs of neurotoxicity. The highest dose of esfenvalerate also resulted in reduced maternal body weight gain throughout the treatment period. In the fetal testes, mRNA expressions of HMG-CoA synthase and reductase, SR-B1, StAR, P450scc, 3βHSD, P450 17A1, and 17βHSD were not affected by exposure to either pyrethroid. No significant change was observed in ex vivo testosterone production. In conclusion, in utero exposure to permethrin or esfenvalerate has no effect on the testosterone biosynthesis pathway in the fetal rat testis up to maternal toxic doses.