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

Xiaoqing Ye, Feixue Li, Jianyun Zhang, Huihui Ma, Dapeng Ji, Xin Huang, Thomas E. Curry, Weiping Liu, Jing Liu

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48 Scopus citations


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.

Original languageEnglish
Pages (from-to)10212-10221
Number of pages10
JournalEnvironmental Science and Technology
Issue number17
StatePublished - Sep 5 2017

Bibliographical note

Funding Information:
The authors declare they have no actual or potential competing financial interests. This work was supported by the National Nature Science Foundation of China (21320102007, 21377113, and 81670971) and Zhejiang Provincial Natural Science Foundation of China (LR15B070001, LY15C120001).

Publisher Copyright:
© 2017 American Chemical Society.

ASJC Scopus subject areas

  • Chemistry (all)
  • Environmental Chemistry


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