Exposure to p,p′-DDE or dieldrin during the reproductive season alters hepatic CYP expression in largemouth bass (Micropterus salmoides)

Abstract

Largemouth bass (LMB) in Central Florida living on sites with high levels of organochlorine pesticides (OCPs) have exhibited poor reproductive success and altered steroid profiles. The mechanism underlying these changes is unknown, however changes in the rate of steroid metabolism could alter steroid homeostasis. Members of the CYP2 and CYP3A families play a significant role in the metabolism of many xenobiotics and endogenous compounds, including sex steroids. Therefore, the goal of this study was to identify members of the CYP2 and CYP3A families in LMB and characterize the effects of OCP exposure on their expression. Full-length clones of two CYP3A isoforms were obtained from LMB liver, CYP3A68 and 3A69, which exhibited significant sequence divergence. Full-length clones for CYP2N14 and CYP2P11 were also obtained from LMB liver. Steady-state mRNA levels of each of these CYPs increased in both sexes between early reproductive phase (December) and peak reproductive phase (March). Expression of CYP3A68 and CYP2P11 was sexually dimorphic during peak reproductive phase with 2-fold higher expression in females and males, respectively. Foodborne exposure to 46 ppm p,p′-DDE or 0.8 ppm dieldrin for 30 days did not have a significant effect on expression of CYPs. However, 4 months exposure to p,p′-DDE induced CYP3A68 and 3A69 expression in both sexes, while dieldrin produced weak induction of CYP3A68 and suppressed CYP3A69 expression in females, but had no effect on males. Neither p,p ′-DDE nor dieldrin significantly altered the expression of CYP2P11 or CYP2N14. This work demonstrates that there are significant changes in CYP expression that occur during LMB reproduction which can be modified by exposure to OCPs.

Persistence of organochlorine chemical residues in fish from the Tombigbee River (Alabama, USA): Continuing risk to wildlife from a former DDT manufacturing facility

“…Dietary exposure to technical DDT has reduced survival in fish at multiple life stages (see review by Jarvinen and Ankley, 1999), and protective thresholds for whole-body total DDT concentrations have been recommended for early life stage, juvenile, and adult fish (Beckvar et al, 2005). In addition, exposure to p,p 0 -DDE, o,p 0 -DDT, and o,p 0 -DDE can affect behavior and disrupt the endocrine and immune systems in fish (Donohoe and Curtis, 1996;Ungerer and Thomas, 1996;Faulk et al, 1999;Milston et al, 2003;Papoulias et al, 2003;GarciaReyero et al, 2006;Barber et al, 2007). Exposure to p,p 0 -DDE has been associated with reduced reproductive success of bird populations; bald eagle (Haliaeetus leucocephalus) and osprey (Pandion haliaetus) are especially susceptible to eggshell thinning after exposure (Anderson and Hickey, 1972;Wiemeyer et al, 1984Wiemeyer et al, , 1988.…”

Assessment of Toxicogenomic Risk Factors in Etiology of Preterm Delivery

“…Report also shows that there is correlation between low level of exposure to benzene, shortened gestation period and polymorphisms with susceptible gene [46]. There is significant high risk of PTD in women, who smoke and carrying genotype CYP1A1 along with GSTT1 [90]. It has also been suggested that there is increased risk of disease like lung, prostate cancer due to exposure of harmful chemicals like OCP and GST null genotype interactions [17,91].…”

“…It has been reported that differential expression of CYP3A gene on chronic exposure to p,p′-DDE and dieldrin but the mechanisms is not yet clear. In mammals p,p′-DDE and dieldrin have been shown to induce CYP3A expression by activation of the constitutive androstane receptor and nuclear receptors in mammals [90]. Further, they have suggested that steroid hormones regulate the expression of CYPs.…”

Metabolism of Pesticides by Human Cytochrome P450 Enzymes In Vitro – A Survey

“…In addition to P450 enzymes, HepaRG cells have a stable expression of phase II enzymes, transporters and nuclear transcription factors over a time period of six weeks in culture (Aninat et al 2006;Anthérieu et al 2010;Kanebratt and Andersson, 2008;Turpeinen et al 2009). Both immunoblotting and reverse transcription polymerase chain reaction (RT-PCR) techniques have been applied to examine the pesticide-CYP induction (Wyde et al 2003;Lemaire et al 2004;Das et al 2006;Sun et al 2005;Johri et al 2007;Barber et al 2007). However, problems in tissue availability, interindividual differences, reproducibility and ethical issues preclude the efficient large-scale use of human primary hepatocytes for induction screening.…”