- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Anne R. Greenlee,¹ Tammy M. Ellis,¹ and Richard L. Berg²

¹Reproductive Toxicology Laboratory and ²Biostatistics Center, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA

Abstract
Occupational exposures to pesticides may increase parental risk of infertility and adverse pregnancy outcomes such as spontaneous abortion, preterm delivery, and congenital anomalies. Less is known about residential use of pesticides and the risks they pose to reproduction and development. In the present study we evaluate environmentally relevant, low-dose exposures to agrochemicals and lawn-care pesticides for their direct effects on mouse preimplantation embryo development, a period corresponding to the first 5-7 days after human conception. Agents tested were those commonly used in the upper midwestern United States, including six herbicides [atrazine, dicamba, metolachlor, 2,4-dichlorophenoxyacetic acid (2,4-D) ], pendimethalin, and mecoprop) , three insecticides (chlorpyrifos, terbufos, and permethrin) , two fungicides (chlorothalonil and mancozeb) , a desiccant (diquat) , and a fertilizer (ammonium nitrate) . Groups of 20-25 embryos were incubated 96 hr in vitro with either individual chemicals or mixtures of chemicals simulating exposures encountered by handling pesticides, inhaling drift, or ingesting contaminated groundwater. Incubating embryos with individual pesticides increased the percentage of apoptosis (cell death) for 11 of 13 chemicals (p 0.05) and reduced development to blastocyst and mean cell number per embryo for 3 of 13 agents (p 0.05) . Mixtures simulating preemergent herbicides, postemergent herbicides, and fungicides increased the percentage of apoptosis in exposed embryos (p 0.05) . Mixtures simulating groundwater contaminants, insecticide formulation, and lawn-care herbicides reduced development to blastocyst and mean cell number per embryo (p 0.05) . Our data demonstrate that pesticide-induced injury can occur very early in development, with a variety of agents, and at concentrations assumed to be without adverse health consequences for humans. Key words: apoptosis, embryo, pesticide mixtures, pesticides, preimplantation development, reference dose. Environ Health Perspect 112:703-709 (2004) . doi:10.1289/ehp.6774 available via http://dx.doi.org/ [Online 22 January 2004]

Address correspondence to A.R. Greenlee, Reproductive Toxicology Laboratory, Marshfield Clinic Research Foundation, 1000 North Oak Ave., Marshfield, WI 54449 USA. Telephone: (715) 389-4012. Fax: (715) 389-3808. E-mail: greenlee.anne@mcrf.mfldclin.edu

We thank D. Wiersma and J. Stier for formulating agrochemical and lawn-care mixtures ; V.P. Eroschenko, Y. Jiang, M.F. Cavieres, J.K. Burmester, B.J. Mitchell, and T. Kronenwetter-Koepel for critically reviewing the manuscript ; and A. Stargardt for preparing this manuscript. We also thank C. Schofield for her assistance with data management, and D. Johnson and R. Jacobson for their assistance with animal care.

This work was funded by the Wisconsin Department of Agriculture, Trade and Consumer Protection, and Marshfield Clinic Research Foundation.

The authors declare they have no competing financial interests.

Received 30 September 2003 ; accepted 21 January 2004.