title: 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.
authors.affiliation: Center for Environmental and Human Toxicology, Department of Physiological Sciences, PO Box 100885, University of Florida, Gainesville, FL 32611, United States. barberd@mail.vetmed.ufl.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Barber
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McNally
authors.forename: Natàlia
authors.initials: N
authors.lastname: Garcia-Reyero
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Denslow
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001492:Bass / Q000502:physiology*; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004026:Dieldrin / Q000633:toxicity*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis; D012098:Reproduction / Q000187:drug effects; D012689:Sequence Homology, Nucleic Acid; D013997:Time Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D007306:Insecticides; D012333:RNA, Messenger; D014874:Water Pollutants, Chemical; D003633:Dichlorodiphenyl Dichloroethylene; D003577:Cytochrome P-450 Enzyme System; D004026:Dieldrin