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Environ Sci Technol. 2017 Sep 5;51(17):10212-10221. doi: 10.1021/acs.est.7b02739. Epub 2017 Aug 8.

Pyrethroid Insecticide Cypermethrin Accelerates Pubertal Onset in Male Mice via Disrupting Hypothalamic-Pituitary-Gonadal Axis.

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MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University , Hangzhou 310058, China.
Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University , Hangzhou 310036, China.
Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University , Hangzhou 310058, China.
Department of Obstetrics and Gynecology, Chandler Medical Center, University of Kentucky , Lexington, Kentucky 40536, United States.


Pyrethroids, a class of insecticides that are widely used worldwide, have been identified as endocrine-disrupting chemicals (EDCs). Our recent epidemiological study reported on an association of increased pyrethroids exposure with elevated gonadotropins levels and earlier pubertal development in Chinese boys. In this study, we further investigated the effects of cypermethrin (CP), one of the most ubiquitous pyrethroid insecticides, on hypothalamic-pituitary-gonadal (HPG) axis and pubertal onset in male animal models. Early postnatal exposure to CP at environmentally relevant doses (0.5, 5, and 50 μg/kg CP) significantly accelerated the age of puberty onset in male mice. Administration of CP induced a dose-dependent increase in serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in male mice. CP did not affect gonadotropin-releasing hormone (GnRH) gene expression in the hypothalamus, but CP at higher concentrations stimulated GnRH pulse frequency. CP could induce the secretion of LH and FSH, as well as the expression of gonadotropin subunit genes [chorionic gonadotropin α (CGα), LHβ, and FSHβ] in pituitary gonadotropes. CP stimulated testosterone production and the expression of steroidogenesis-related genes [steroidogenic acute regulatory (StAR) and Cytochrome p 450, family 11, subfamily A, polypeptide 1 (CYP11A1)] in testicular Leydig cells. The interference with hypothalamic sodium channels as well as calcium channels in pituitary gonadotropes and testicular Leydig cells was responsible for CP-induced HPG axis maturation. Our findings established in animal models provide further evidence for the biological plausibility of pyrethroid exposure as a potentially environmental contributor to earlier puberty in males.

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