Embryonic exposure to the widely-used herbicide atrazine disrupts meiosis and normal follicle formation in female mice

Aurore Gely-Pernot,Fatima Smagulova,Christine Kervarrec,Sergei Tevosian,Frank Giton,Pierre-Yves Kernanec,Souhila Saci,Chunxiang Hao,Severine Mazaud-Guittot

doi:10.1038/s41598-017-03738-1

Abstract

The widely-used herbicide atrazine (ATZ) is detected in ground and surface water in many countries. Several studies in animals have demonstrated that ATZ has endocrine-disrupting effects on male and female reproduction in many vertebrate species. In this study, we investigated the effects of ATZ exposure on meiosis, a key step in gametogenesis in mammals. The treatment was initiated before oocyte entry into meiosis, which occurs during the embryonic period in females. We found that embryonic exposure to ATZ increases the level of 8-oxo-guanine in the nucleus of meiotic cells, reflecting oxidative stress and affecting meiotic double-strand break repair, chromosome synapsis and crossover numbers. Finally, embryonic exposure to ATZ reduces the number of primordial follicles and increases the incidence of multi-oocyte follicles in adult mice. Our data demonstrate that embryonic exposure to ATZ disrupts prophase I of meiosis and affects normal follicle formation in female mice.

Highlights

Pesticides and herbicides are widely used in agriculture in many countries, and their negative impacts on human health and wildlife are still not well understood
The aim of the present study was to investigate whether prenatal exposure to ATZ affects female meiosis and whether ATZ exposure during the early developmental program will impact oocyte maturation in the adult stage
We analyzed major meiotic events, which occur during embryonic development, and we investigated the effects of ATZ on ovarian folliculogenesis after birth, at puberty and in aging female mice

Summary

Introduction

Pesticides and herbicides are widely used in agriculture in many countries, and their negative impacts on human health and wildlife are still not well understood. Low levels of ATZ metabolites in pregnant women are associated with low birth weight in newborns[12, 13], suggesting possible negative ATZ-related effects on the early developmental program. This fact raises a serious concern of ATZ safety for humans. The hormonal changes in exposed pigs are associated with morphological effects, including the appearance of multiple ovarian follicular cysts[25] Taken together, these studies show ATZ-related effects on ovarian morphology and endocrine function in animals exposed at the adult stage. We hypothesize that embryonic exposure to ATZ would impact prophase I of meiosis and impose changes that could affect the oocyte developmental program

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