Meeting Abstract
P3.70 Sunday, Jan. 6 Chlorpyrifos is an endocrine disruptor in the human placenta via effects on steroidogenic and elimination enzymes NGIRAKESAU, I.K.*; SATO, B.L.M.; COLLIER, A.C.; John A. Burns School of Medicine, University of Hawaii at Manoa; John A. Burns School of Medicine, University of Hawaii at Manoa; John A. Burns School of Medicine, University of Hawaii at Manoa ivanda.school@gmail.com
Chlorpyrifos (CPF), a widely used organophosphate pesticide, is a chemical of concern to the Environmental Protection Agency. In this study, we hypothesized a direct target of CPF toxicity is placental function and integrity. To determine CPF effects on placental cell viability and function, the BeWo cell line was treated with a log-scale range of Chlorpyrifos 0.1pM – 100 μM, spanning levels determined in maternal blood during pregnancy and including one log below and one log above these levels. Cells were evaluated for cell death (LDH assay) and metabolic/mitochondrial viability (MTT assay). Additionally, CPF effects on essential placental endocrine function was assessed by determining secretions of the sex hormones progesterone, estradiol, estrone and estriol as well as the placental hormone βHCG. At the concentrations used, CPF did not significantly kill cells or decrease viability, except at 100 μM where cell death/viability was 50% in both assays. Despite this, even in concentrations where cell viability was not compromised, CPF inhibited sex hormone secretion. Progesterone secretion was significantly decreased, but we determined that this was caused by the solvent vehicle (DMSO) not the CPF. In contrast, for the estrogenic hormones, DMSO did not significantly affect sex steroid secretion but estrone secretion from BeWo cells was significantly increased. The mechanisms behind changes in placental steroid secretion were investigated by determining activities of steroidogenic and steroid elimination enzymes (aromatase, 3βHSD, glucuronosyltransferases and sulfotransferases). These studies suggest that CPF may have endocrine disrupting effects in placental cells through deregulation of estrogenic hormone balance. This is a potential mechanism for CPF effects on pregnancy maintenance, fetal development and parturition.
