Pyrethroids Exposure Accelerates Male Pubertal Development

Presentation Number: OR15-5
Date of Presentation: April 1st, 2017

Jing Liu*1, Xiaoqing Ye2, Feixue Li3 and Weiping Liu2
1Zhejiang University, China, 2Zhejiang University, 3Hangzhou Normal University, China

Abstract

Exposure to endocrine-disrupting chemicals (EDCs) has been associated with shifting pubertal timing which increases the risk for diseases later in adult life (1). Pyrethroids, one of the most ubiquitous pesticides that account for greater than 30% of currently global insecticide usage, have been identified as EDCs (2). However, little data regarding pyrethroid exposure and puberty are available, and the mechanism(s) by which pyrethroids affect puberty remains poorly understood.

Here, we recognize pyrethroids as a new environmental contributor to the observed secular trend toward earlier male sexual maturity. For the first time to our knowledge, this work reveal a highly significant and positive association between pyrethroids exposure and gonadotropins levels in 463 Chinese boys (p<0.001), in which a 10% increase in 3-PBA (a common urinary metabolite of pyrethroids) is associated with an approximate 4% increase in LH and FSH. Boys with increased urinary levels of 3-PBA have a significantly increased risk of earlier pubertal onset, in which the odds of being in an advanced pubertal stage are increase by 73% to 110%.

Because it is difficult to test the direct causality of environmental risk factors in humans, this investigation further sought to identify the mechanism(s) by which the pyrethroids act to alter the onset of puberty using in vitro and in vivo experimental rodent models. Consistent with the human data, our animal study shows that postnatal exposure to a widely used pyrethroid pesticide, cypermethrin (CP), can accelerate pubertal timing and induce circulating levels of gonadotropins and testosterone in male mice. We demonstrate that the acceleration of puberty onset by CP is independent of hypothalamic responsiveness and that the induction of gonadotropins and testosterone results from the direct effects of CP on pituitary gonadotropes and testis. CP regulates gonadotropins synthesis and the expression of gonadotropin subunit genes through the Ca2+/PKC/ERK/IEGs transduction pathways in pituitary gonadotropes. CP induces testosterone synthesis and steroidogenesis-related gene expression in testicular Leydig cells via interference with voltage-gated calcium channels (VGCCs) pathway. Our findings reveal the activation of VGCCs in pituitary gonadotropes and testicular Leydig cells as a newly discovered mechanism of pyrethroid-induced early puberty onset in the male.

In conclusion, this is the first study to provide evidence that environmental exposure to pyrethroids at levels actually present in human is associated with measurable effects on male pubertal development. Given the growing use of pyrethroid insecticides, our findings have important implications for the assessment of children’s health risk from these insecticides. More broadly, this study significantly expands the understanding of the possible mechanisms involved in humans.

 

Nothing to Disclose: JL, XY, FL, WL