PROCINE MODEL FOR ENDOCRINE DISRUPTING CHEMICALS

Mississippi State University, Mississippi State MS

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Abstract

DESCRIPTION (provided by applicant): Disruption or modification of endocrine homeostasis during development by agricultural pesticides possessing estrogen-like or estrogen disruptive activities has been suggested on me basis of reports of abnormal sexual development observed in wildlife species and rodent animal models. Of great concern is the impact these types of environmental contaminants may have on human health, in particular, the effects of exposure on fetal development during organogenesis or differentiation of the endocrine and nervous systems. However, the lack of an ideal animal model to examine potential adverse effects in humans resulting from in utero exposure has hampered progress in this area. Typical laboratory rodents are not ideal models for human reproductive physiology. Thus, the primary goal of this study is to develop the pregnant pig as a novel animal model for investigating the impact of in utero exposure to estrogenic and non-estrogenic endocrine-active agricultural pesticides on sexual dimorphism in humans. The rationale for selecting the pig, as opposed to the traditional rodent model, is based on the fact that porcine physiology is remarkably similar to that of humans with particular regard to the reproductive and endocrine systems. In addition, a need exists to test the predictive value of amniotic fluid as a useful surrogate marker of fetal exposure to environmental contaminants during critical stages of development. Xenobiotics and naturally occurring compounds that mimic endogenous hormones have been found in human serum, breast milk and umbilical cord blood, but these fluids are not good indices of in utero contamination. Exposure estimation is often the weakest link in assessing risks to human health posed by environmental contaminants. Since amniocentesis is a relatively routine procedure performed during human pregnancy, the pig makes sampling of amniotic fluid feasible, which would be difficult to perform in the rodent model without compromising pregnancy. We propose that the pregnant pig will serve as a physiologically representative animal model for investigating the impact and mechanisms ofaction of endocrine disruptive chemicals on human sexual development. Moreover, we hypothesize that high concentration of agricultural pesticides containing amniotic fluid will be associated with aberrant reproductive development and lower birth weight of piglets. To undertake these goals, we have formulated the following two specific aims: 1) we will a) verify that the pregnant pig is a suitable animal model for assessing the impact of in utero exposure to endocrine-disruptive chemicals on sexual development, and b) test the usefulness of monitoring amniotic fluid for endocrine disruptive chemical exposure for hazard assessment. 2) we will use the pregnant pig model to investigate the endocrine disruptive potential of in utero exposure to two agricultural pesticides with known estrogen-like or estrogen disruptive activities (e.g., atrazine and methoxychlor) leading to reproductive developmental side effects.