Abstract

Pesticide exposure during fetal life can lead to low birth weight and is commonly observed in reproductive toxicology studies. Associations have also been found in low birth weight babies born from pesticide-exposed gardeners. Since low birth weight is also linked to metabolic disorders, it can be speculated that early life exposure to pesticides could increase the risk of becoming obese or developing diabetes later in life. We have analyzed potential long-term effects of gestational and lactational exposure to a low dose mixture of six pesticides that individually can cause low birth weight: Cyromazine, MCPB, Pirimicarb, Quinoclamine, Thiram, and Ziram. Exposed male offspring, who were smaller than controls, displayed some degree of catch-up growth. Insulin and glucagon regulation was not significantly affected, and analyses of liver and pancreas did not reveal obvious histopathological effects. Efforts towards identifying potential biomarkers of metabolic disease-risk did not result in any strong candidates, albeit leptin levels were altered in exposed animals. In fat tissues, the key genes Lep, Nmb and Nmbr were altered in high dosed offspring, and were differentially expressed between sexes. Our results suggest that early-life exposure to pesticides may contribute to the development of metabolic disorders later in life.

Highlights

  • Fetal programming is a tightly regulated, highly complex process that ensures the development of viable offspring

  • Associations were found between high pesticide exposure during early pregnancy and low birth weight, but it was found that the high-exposure, low birth weight children had a stronger propensity for increase in Body Mass Index (BMI) towards school age

  • We previously reported a lower birth weight in rat offspring following exposure to the low dose mixture of six pesticides administered from gestational day 7 until pup day 1614

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Summary

Introduction

Fetal programming is a tightly regulated, highly complex process that ensures the development of viable offspring. The prevailing view is that the fetus responds to its immediate environment, whereby complex regulatory pathways and adaptive responses are initiated so that the fetus become best equipped for postnatal life[1] The flipside to such adaptive responses is that a low birth weight is a risk factor for developing various late-onset diseases, including obesity and type-2 diabetes[2]. The pesticide doses were singularly below No Observed Adverse Effect Levels (NOAELs) for decreased birth weight and the effect-outcome was driven by the combined action of more than one pesticide These results, together with other observations linking low birth weight with fetal exposure to environmental chemicals[9,13], encouraged us to investigate whether the rat offspring from our study would develop signs of metabolic syndrome as they grew older, and to potentially identify early biomarkers for late onset metabolic diseases

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