Atrazine Exposure and Reproductive Dysfunction through the Hypothalamus-Pituitary-Gonadal (HPG) Axis.

Jennifer Freeman,Sara Wirbisky

doi:10.3390/toxics3040414

Abstract

Endocrine disrupting chemicals (EDC) are exogenous agents that alter endogenous hormone signaling pathways. These chemicals target the neuroendocrine system which is composed of organs throughout the body that work alongside the central nervous system to regulate biological processes. Of primary importance is the hypothalamic-pituitary-gonadal (HPG) axis which is vital for maintaining proper reproductive function. Atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine) is a pre-emergent herbicide used to prevent the growth of weeds on various crops. This herbicide is reported to widely contaminate potable water supplies everywhere it is applied. As such, the European Union banned the use of atrazine in 2004. Currently the United States Environmental Protection Agency regulates atrazine at 3 parts per billion (ppb; μg/L) in drinking water, while the World Health Organization recently changed their drinking water guideline to 100 ppb. Atrazine is implicated to be an EDC that alters reproductive dysfunction by targeting the HPG axis. However, questions remain as to the human health risks associated with atrazine exposure with studies reporting mixed results on the ability of atrazine to alter the HPG axis. In this review, the current findings for atrazine’s effects on the HPG axis are examined in mammalian, anuran, and fish models and in epidemiological studies.

Highlights

The endocrine system is comprised of numerous organs throughout the body that work in tandem with the central nervous system (CNS) to regulate biological processes
While questions still remain on human health relevancy of doses at which these adverse effects are observed, results from these studies begin to provide insight into the reproductive dysfunction observed in epidemiological studies
The primary focus of the endocrine disrupting effects of atrazine on the male reproductive system has progressed over the years but is still under investigation

Summary

Introduction

The endocrine system is comprised of numerous organs throughout the body that work in tandem with the central nervous system (CNS) to regulate biological processes. Epidemiological studies have focused on the association between EDC exposure and various adverse health states, diseases, and disorders including reproductive dysfunction [7,8,9,10]. Numerous challenges are identified and need to be overcome when aiming to understand the mechanisms of action of EDCs. First, is the variable persistence in the body and in the environment which can range from a few days (e.g., bisphenol A (BPA)) to years (e.g., 1,1-dichloro-2,2-bis(pchlorophenyl) ethylene (DDE)) [15]. Is the variable persistence in the body and in the environment which can range from a few days (e.g., bisphenol A (BPA)) to years (e.g., 1,1-dichloro-2,2-bis(pchlorophenyl) ethylene (DDE)) [15] This variation in persistence can make linking EDC exposure to adverse health outcomes a challenge. Literature investigating the effects of atrazine on the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-thyroid (HPT) axes, and neurotransmitter studies were excluded

The Effects of Atrazine on Female Reproductive Function in Mammalian Models

Gestational Atrazine Exposure in Females

Peripubertal Atrazine Exposure in Females

Adulthood Atrazine Exposure in Females

Cellular and Genetic Mechanisms of Reproductive Dysfunction in Females

Tissue Levels of Atrazine in Females

Conclusions

The Effects of Atrazine on Male Reproductive Function in Mammalian Models

Gestational Atrazine Exposure in Males

Peripubertal Atrazine Exposure in Males

Adulthood Atrazine Exposure in Males

Developmental Origins of Atrazine Toxicity