Simazine, a triazine herbicide, disrupts swine granulosa cell functions

Abstract

The triazine herbicide simazine is a pesticide commonly detected in surface and ground waters, although banned in most European countries since 2004. Concerns for humans and animal health result from its potential endocrine disrupting action, that can lead to reproductive disorders. The present in vitro study was undertaken to study simazine effects on swine granulosa cell function, namely cell viability, proliferation, steroidogenesis and NO production. Moreover, the ability of this substance to interfere with the angiogenetic process, a crucial event in reproductive function, was taken into account. Our data document that simazine treatment, at 0.1 or 10 μM concentration levels, stimulates granulosa cell proliferation and viability and impairs steroidogenesis, increasing in particular progesterone production. In addition, the in vitro angiogenesis bioassay revealed a significant simazine stimulatory effect on immortalized porcine Aortic Endothelial Cell proliferation. Collectively, these results show that simazine can display disruptive effects on ovarian cell functional parameters, possibly resulting in reproductive dysfunction. This hypothesis is also supported by the observed pro-angiogenetic properties of this herbicide, as already suggested for different endocrine disruptors.

Toxicogenomics Data for Chemical Safety Assessment and Development of New Approach Methodologies: An Adverse Outcome Pathway‐Based Approach

“…Simazine is a triazine herbicide whose use has been banned in most European countries for nearly two decades. [ 42 ] Simazine has now been recognized, similarly to the other compounds, as an endocrine disrupter. [ 42 ] Interestingly, the enrichment analysis for simazine highlighted AOPs related to the development of adenomas and carcinomas through endocrine disrupting activities (e.g., Aop:107 titled “Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat”) as well as direct disruption of the GnRH pulse (File S1, Supporting Information).…”

“…[ 42 ] Simazine has now been recognized, similarly to the other compounds, as an endocrine disrupter. [ 42 ] Interestingly, the enrichment analysis for simazine highlighted AOPs related to the development of adenomas and carcinomas through endocrine disrupting activities (e.g., Aop:107 titled “Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat”) as well as direct disruption of the GnRH pulse (File S1, Supporting Information). Although multiple in vivo and in silico evidence also indicate permethrin as possible endocrine disruptor, [ 43 , 44 ] no endocrine related pathways are present in the top enriched AOPs.…”

Molecular annotation of AOPs guides the development of the next generation mechanistic chemical safety assessment and new approach methods

“…Similarly, our framework highlights both the "PPARalpha-dependent liver cancer" and "Cyp2E1 Activation Leading to Liver Cancer" AOPs. Simazine is a triazine herbicide whose use has been banned in most European countries for nearly two decades (42). Simazine has now been recognised, similarly to the other compounds, as an endocrine disrupter (42).…”

“…Simazine is a triazine herbicide whose use has been banned in most European countries for nearly two decades (42). Simazine has now been recognised, similarly to the other compounds, as an endocrine disrupter (42). Interestingly, the enrichment analysis for simazine highlighted AOPs related to the development of adenomas and carcinomas through endocrine disrupting activities (e.g., Aop:107 titled "Constitutive androstane receptor activation leading to hepatocellular adenomas and carcinomas in the mouse and the rat") as well as direct disruption of the GnRH pulse (Supplementary File 1).…”