Effects of Developmental Deltamethrin Exposure on White Adipose Tissue Gene Expression

J BIOCHEM MOLECULAR TOXICOLOGYVolume 27, Number 2, 2013

Effects of Developmental Deltamethrin Exposure onWhite Adipose Tissue Gene ExpressionLaura E. Armstrong,1 Maureen V. Driscoll,1 Vijay R. More,1 Ajay C. Donepudi,1

Jialin Xu,1 Angela Baker,2 Lauren M. Aleksunes,3 Jason R. Richardson,2

and Angela L. Slitt1

1Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA; E-mail: [email protected] of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA3Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA

Received 19 November 2012; revised 23 January 2013; accepted 23 January 2013

ABSTRACT: Deltamethrin, a type II pyrethroid, isa widely used insecticide. The purpose of this studywas to determine whether perinatal deltamethrin ex-posure altered the expression of adipogenic and li-pogenic genes in white adipose tissue (WAT) in adultpups. C57BL/6 pregnant mice were administered 0, 1,or 3 mg/kg of deltamethrin orally every 3 days through-out gestation and lactation. Offspring were weanedon postnatal day 25, and WAT was collected from5-month-old male mice. Perinatal deltamethrin expo-sure decreased the mRNA expression of adipogenesis-related transcription factors Pparγ , Cebpα, and li-pogenic genes Srebp1c, Acc-1, Cd36, Lpl, Scd-1; alongwith Nrf2 and target genes Nqo1 and Gclc at the1 mg/kg treatment. Cytokine expression of Fas/Tnf-R and Cd209e at the 1 mg/kg treatment was signifi-cantly decreased, and expression of Tnf, Cd11c, andFas/Tnf-R was decreased at the 3 mg/kg treatment.Developmental deltamethrin exposure did not overtlyaffect body weight or adipose weight, but decreasedmRNA expression of specific genes that may poten-

Correspondence to: A. L. Slitt.This article was originally published on 11 February 2013.

Subsequently, the Figures 1 and 2 were updated and an additionalauthor was added to the paper. The corrected version was publishedon 28 February 2013.

This work was presented, in part, at the Annual Society of Tox-icology meeting held March 12–15, 2012, in San Francisco, CA and atthe Northeast Society of Toxicology meeting held October 19, 2012 atSalve Regina University, Newport, RI.

Contract Grant Sponsor: National Institute of Health.Contract Grant Numbers: 4R01ES016042, 5K22ES013782,

R01ES015991, T32ES007148, and P30ES005022.Contract Grant Sponsor: National Center for Research Re-

sources.Contract Grant Number: 5P20RR016457.Contract Grant Sponsor: Institute for General Medical Science.Contract Grant Number: P20 GM103430.

C© 2013 Wiley Periodicals, Inc.

tially disrupt normal adipogenesis and lipid and glu-cose metabolism if the offspring are challenged bychanges in diet or environment. C© 2013 Wiley Peri-odicals, Inc. J Biochem Mol Toxicol 27:165–171, 2013;View this article online at wileyonlinelibrary.com. DOI10.1002/jbt.21477

KEYWORDS: Deltamethrin; White Adipose Tissue;Adipogenesis; Perinatal; Pyrethroid

INTRODUCTION

Pyrethroids are synthetic chemicals modeled afterthe naturally occurring pyrethrins, found in chrysan-themums [1]. Type I and type II pyrethroids are com-monly used as potent and effective insecticides foragricultural and public health applications [2] andcan easily enter the exoskeleton of insects. These ax-onic poisons cause paralysis and ultimately death ofthe organism by keeping sodium channels open inthe neuronal membranes. Type II pyrethroids, suchas deltamethrin, are defined by an α-cyano groupthat is known to produce a long lasting inhibition ofvoltage-activated sodium channels [1, 2]. Pyrethroidpesticides are often thought of as “safer” alternativesto the more toxic organophosphates because of theirlow mammalian toxicity. This relatively low toxicityis attributed to a combination of efficient detoxifica-tion mechanisms in mammals [3] and lower sensitiv-ity of ion channels [2]. However, metabolic detoxifi-cation mechanisms are not fully developed in veryyoung mammals, potentially increasing susceptibilityto pyrethroids in this population [4]. This is particularlycrucial because pyrethroid use has increased tremen-dously since the cancellation or reduction in the use of

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166 ARMSTRONG ET AL. Volume 27, Number 2, 2013

many organophosphorus pesticides [5]. In recent years,significant levels of pyrethroid metabolites, includingthose of deltamethrin, have been found in the urineof pregnant women and children [6–9]. Furthermore,deltamethrin, which is widely used to control malariavectors, has also been detected in the breast milk ofSouth African women [10]. The latter data pose ques-tions regarding the safety of deltamethrin, as develop-mental neurotoxicity and other adverse developmentaleffects are currently being studied in these susceptiblepopulations [1].

Adipose tissue is a lipophilic tissue that is metabol-ically active and essential for the proper maintenanceof systemic energy balance. Adipogenesis requires ahighly regulated cascade of transcription factors, in-cluding C/EBP family and Pparγ , which regulatethe differentiation of preadipocytes to adipocytes [11].Most recently, this cascade of transcription factors hasbeen proven to be regulated by Nrf2, a well-definedtranscription factor of oxidative stress [12, 13]. Thethree major functions of adipose tissue are lipid storageand mobilization, glucose homeostasis, and endocrinefunction, involving secretion of hormones, cytokines,and transcription factors [11,14]. Changes in the expres-sion of transcription factors involved in adipocyte dif-ferentiation during development can lead to dysfunc-tion in the metabolic and endocrine functions of whiteadipose tissue (WAT), as demonstrated by gene knock-down, knockout, and induction studies [11, 14]. Whencharacterizing deltamethrin as a safe pesticide, TheWorld Health Organization (WHO) observed lowerbody weight (BW) gain in adult rats that were orally ad-ministered the pesticide, decreased mean fetal weightswith a perinatal high dose of 10 mg/kg BW, and adose-related decrease in BW of postnatal mice [15].Despite increased research on the developmental tox-icology of pyrethroids, to our knowledge, no studieshave addressed whether exposure to pyrethroids dur-ing developmental stages affects adipose tissue devel-opment and homeostasis. Therefore, the purpose ofthis study was to address the potential metabolic ef-fects of perinatal deltamethrin exposure in WAT, toaddress previously described changes in BW duringdevelopment.

MATERIALS AND METHODS

Animals

Eight-week-old female and male C57BL/6J micepurchased from Jackson Laboratory (Bar Harbor, ME)were used. Mice were maintained on a 12:12 light/darkcycle with food and water available ad libitum. All pro-cedures were conducted in accordance with the NIHGuide for Care and Use of Laboratory Animals and ap-

proved by the Institutional Animal Care and Use Com-mittee at Robert Wood Johnson Medical School.

Treatment

10-week-old female C57BL/6J mice were individ-ually housed and mated with C57BL/6J males. Uponidentification of a vaginal plug, males were removedand single-housed female mice were administered 0(control), 1, or 3 mg/kg BW deltamethrin (ChemSer-vice, West Chester, PA), dissolved in corn oil and mixedwith peanut butter (∼100 mg; Skippy Creamy PeanutButter) every 3 days throughout gestation and lacta-tion as described previously [16–18]. Mice were mon-itored to ensure total consumption of the treatmentdose, which generally occurred within 10 min. Thisadministration method reduces handling stress associ-ated with injections during pregnancy and most closelymimics human oral exposure conditions [16, 17].

The dose selected in this study is one-fourth ofthe developmental No observable adverse effect level(NOAEL) [19]. Unfortunately, the rapid metabolismof pyrethroids has made dose extrapolation difficult.There have been no comparative studies in rodentand humans to determine half-lives of the parent com-pound, but separate studies have presented the half-lifeof deltmethrin, in humans and rats, to appear to be in asimilar range of several hours. It should be noted thatrecent pharmacokinetic modeling in rats predicted thathumans would experience a higher brain concentra-tion of deltamethrin compared to rodents, most likelybecause humans do not have plasma carboxylesteraseactivity [20].

The offspring were weaned at postnatal day 25,and once weaned; offspring received no additional ex-posure to deltamethrin. The time point of 5 monthswas selected because tissues were being shared from acohort, from a study being conducted by Dr. Richard-son’s group for the primary purpose of developmen-tal deltamethrin effects on behavior. These cohortshad been assessed for neurobehavioral changes, and5 months was determined to be an appropriate time ofnecropsy for Dr. Richardson’s study. As 5 months rep-resent adulthood and mature adipose tissue, WAT wasevaluated for changes in expression of genes relatedto adipogenesis, lipid synthesis, glucose uptake, andinflammation.

Prior to sacrifice, blood glucose concentrationswere obtained via tail vein nick and measured usinga TRUEtrackTM glucometer. Animals were not fastedprior to sacrifice. Mice were sacrificed by CO2 inhala-tion followed by cardiac puncture for blood collectionat 5 months of age. Blood was centrifuged at 14,000×gfor 10 min to obtain serum. WAT from the abdomenwas removed and snap frozen in liquid nitrogen.

J Biochem Molecular Toxicology DOI 10.1002/jbt

Volume 27, Number 2, 2013 DEVELOPMENTAL DELTAMETHRIN AND ADIPOSE TISSUE 167

Samples were stored at –80◦C until shipment to Uni-versity of Rhode Island on dry ice. Dosing of mice andsample collection was carried out by the laboratory ofDr. Jason Richardson at the University of Medicine andDentistry of New Jersey, Piscataway, NJ.

RNA Extraction

Perinatal exposure to deltamethrin causes postna-tal behavioral changes in adult male, but not female off-spring (Richardson et al., submitted). For this reason,adult male mice were selected for the current investi-gation. Total RNA was isolated from 50–100 mg frozenWAT from the male 5-month cohort via homogeniza-tion in TrizolTM lysis buffer (Life Technologies, GrandIsland, NY) followed by chloroform-isopropanol ex-traction. The RNA concentration was determined bymeasuring UV absorbance of the sample at 260 nm us-ing NanoDropTM (Wilmington, DE), and RNA integritywas confirmed by the presence of distinct 18S and 28Sbands using formaldehyde-agarose gel electrophoresis.RNA samples were stored at –80◦C until utilized.

Quantigene Plex 2.0 Assay

Total RNA was applied to the QuantigenePlex (Affymetrix, Santa Clara, CA) and hybridizedovernight at 54◦C with specific mRNA capture beadsand capture probes. The following day, the sampleswere hybridized with preamplifier followed by am-plifier incubation and a biotinylated label probe for1 h at 50◦C followed by application of streptavidin-conjugated phycoerythrin detection probe for 30 minat room temperature. The plex was analyzed on a Lu-minex Bio-Plex 200 array reader with Luminex 100xMAP technology (Austin, TX). mRNA expressionwas normalized to the Rpl13a housekeeping gene,which was not significantly different between treat-ment groups. Only male gene expression in adiposetissue was determined in an attempt to reduce gendervariability as a confounding factor.

qPCR mRNA Quantification

qPCR was utilized to measure the mRNA geneexpression of important genes in WAT that were notavailable on the Quantigene Plex used. Total RNAwas utilized as a template to make complementaryDNA via the polymerase chain reaction (PCR) follow-ing the specified protocol for a Transcriptor First StrandcDNA synthesis kit (Roche Applied Sciences Cat. #:04897030001). The cDNA was amplified and quantifiedfor gene expression levels using LightCycler 480 R© SYBRGreen I Master chemistry (Roche Applied Sciences) for

qPCR determination of Nrf2, Nqo1, and Gclc. Rpl13awas used as the housekeeping gene for normalization.

Statistical Analysis

Statistical analyses of data were performed using aone-way analysis of variance and further analyzed bya Dunnett’s Test post hoc test to determine significantdifference between control and each treatment group.p < 0.05 was considered statistically significant. Unlessotherwise stated, all data were presented as mean ±SE of nine animals (control) and eight animals (1 and3 mg/kg doses). Statistica v.9 (StatSoft, Tulsa, OK) wasused for statistical analysis.

RESULTS

Effect of Developmental Exposure onPhysiological Parameters and theExpression of Genes Related to GlucoseHomeostasis in WAT

The physiological data collected prior to necropsyshowed no significant differences in BW between pupsthat were exposed to vehicle or deltamethrin duringdevelopment (Figure 1A), and the blood glucose con-centration was similar between both treatments com-pared to control (Figure 1B). The expression of a pre-dominant insulin-responsive gene and two essentialglucose transporters in WAT was determined usingLuminex 100xMAP technology. Figure 1C shows thatthere were some differences between the gene expres-sion of insulin responsive genes and glucose trans-port genes, Irs-1, Glut4, and Glut2, in WAT. Devel-opmental deltamethrin (1 mg/kg) exposure decreasedGlut4 (31%), and both deltamethrin doses significantlydecreased Glut2 mRNA (83%, 82%). No changes inIrs-1 mRNA expression were observed. These dataare supported by the blood glucose measurementsthat were also found to be unchanged with perinataldeltamethrin exposure.

Effect of Developmental DeltamethrinExposure on Expression of Genes Related toAdipogenesis and Lipogenesis in WAT

There were no significant differences in BW be-tween the male pups that were exposed to vehicleor deltamethrin during development at 5 months ofage (Figure 1A), but because of the significant de-crease in mRNA expression in glucose transport theprimary functions of adipose tissue, development ofadipocytes, and lipid transport and metabolism shouldbe described. Expression levels of lipogeneic genesin WAT and the well-described regulators of adipo-genesis were determined using Luminex 100xMAP



FIGURE 1. Body weight was used to describe any potentialmetabolic effects of perinatal deltamethrin exposure, along withblood glucose concentration and mRNA gene expression of keyfactors in insulin response of WAT to describe potential effects onglucose homeostasis. Body weights of 5-month-old male mice weretaken prior to sacrifice. (A) Average body weight (g) of each treat-ment group expressed as a mean BW ± SEM (n = 6–7). (B) Bloodglucose level taken at time of necropsy of 5-month-old adult malemice expressed as a mean BG ± SEM (n = 5–6). mRNA gene ex-pression data in WAT of 5-month-old adult male mouse pups fromdams exposed to 0, 1, or 3 mg deltamethrin/kg every 3 days dur-ing getation and lactation. Total RNA was isolated from WAT, andmRNA levels were quantified by Quantigene Plex 2.0 assay. All geneexpression data were normalized to Rpl13a (no significant changein gene expression) and are expressed as mean ± SEM (n = 8–9).(C) Insulin responsive and glucose transport: Irs-1, Glut-4, Glut-2 mRNA expression. mRNA gene expression data in WAT of 5-month-old adult male mouse pups from dams exposed to 0, 1, or3 mg deltamethrin/kg every 3 days during gestation and lactation.* and # represent statistical difference between control and treatmentdoses (p < 0.05 and p < 0.005, respectively).

FIGURE 2. mRNA gene expression data in WAT of 5-month-oldadult male mouse pups from dams exposed to 0, 1, or 3 mgdeltamethrin/kg every 3 days during gestation and lactation. To-tal RNA was isolated from WAT, and mRNA levels were quantifiedby Quantigene Plex 2.0 assay. All gene expression data were nor-malized to Rpl13a (no significant change in gene expression) and areexpressed as mean ± SEM (n = 8–9). (A) Lipogenic genes: Srebp1,Acc-1, Fabp4, Cd36, Lpl, Scd-1 mRNA expression. (B) Regulators ofadipogenesis: Pparγ , Cebpα, Cebpβ mRNA expression. (C) mRNAgene expression for Nrf2, Nqo1, and Gclc was quantified by a Light-cycler 480 SYBR green qPCR method. Nrf2, Nqo1, and Gclc mRNAexpression *and # represent statistical difference between control andtreatment doses (p < 0.05 and p < 0.005, respectively).

technology. Significant decreases in the expression oflipogenic genes Srebp1 (28%), Acc-1 (44%), Fabp4(19%), Cd36 (21%), Lpl (22%), and Scd-1 (22%) wereobserved in the 1-mg/kg treatment group comparedto control. Furthermore, no changes in the expressionof any of the lipogeneic genes measured were ob-served in the 3-mg/kg treatment group (Figure 2A).The relative gene expression of adipogenesis regulators(Pparγ , Cebpα, and Cebpβ) is illustrated in Figure 2B.Perinatal deltamethrin exposure (1 mg/kg) decreasedPparγ and Cebpα expression in WAT 28% and 32%,respectively, compared to vehicle controls. Cebpβ



0

0.2

0.4

0.6

0.8

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1.2

1.4

Tnf Ccl-2 Cd11c Fas/Tnf-R Cd209e

Rel

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AT

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Control 1 mg/kg 3 mg/kg

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FIGURE 3. mRNA gene expression of cytokines in WAT of 5-month-old adult male pups from dams exposed to 0, 1, or 3 mgdeltamethrin/kg every 3 days during gestation and lactation. TotalRNA was isolated from WAT, and mRNA levels were quantified byQuantigene Plex 2.0 assay. All gene expression data were normal-ized to Rpl13a (no significant change in gene expression) and areexpressed as mean ± SEM (n = 8–9) Cytokines: Tnf, Ccl-2, Cd11c,Fas/Tnf-R (M1 macrophage markers) and Cd209e (M2 macrophagemarker). * and # represent statistical difference between control andtreatment doses (p < 0.05 and p < 0.005, respectively).

expression in WAT was similar for all groups. A po-tential further upstream regulator of adipogenesis andlipid metabolism in adipose issue is Nrf2 [13, 21]. Nrf2and its target genes Nqo1 and Gclc were measured byqPCR, using LightCycler 480 R© SYBR Green chemistryand instrumentation, and presented in Figure 2C. Nrf2,Nqo1, and Gclc were all significantly downregulatedat the 1 mg/kg treatment. Nrf2 was decreased to 27%,Nqo1 to 13%, and Gclc to 11% of the control. The de-creased mRNA of the downstream target genes of Nrf2suggests the decreased protein level or activity of Nrf2,which if a decrease could potentially explain the down-regulation of gene expression by perinatal deltamethrinexposure.

Effect of Developmental DeltamethrinExposure on Cytokine mRNA Expressionin WAT

Tnf, Ccl-2, Cd11c, Fas/Tnf-R, Cd209e, and Il4 cy-tokine levels in WAT were measured in 5-month-oldmale pups that were exposed to deltamethrin via peri-natal exposure. Significant decreases in cytokine lev-els for both treatment groups were observed whencompared to the control group (Figure 3). Tnf levelsdecreased 63% in the 3-mg/kg treatment group, com-pared to the control group. Tnf expression was sim-ilar between control pups and pups exposed to the1 mg/kg developmental deltamethrin dose. Cd11c ex-pression was only decreased in the 3-mg/kg groupby 66% compared to control. Tnf-R expression wasmarkedly decreased 70% (1 mg deltamethrin/kg) and75% (3 mg deltamethrin/kg) when compared to the

control group. Cd209e levels were decreased to 39%of control in the 1-mg/kg treatment group but weresimilar to controls in the 3-mg deltamethrin/kg group.There were no significant differences in Ccl-2 and Il4cytokine levels compared to the control in either the 1-or 3-mg/kg treatment group.

DISCUSSION

Deltamethrin and other pyrethroids have been es-tablished as safe pesticides based on data showing de-creased toxicity in mammals from rapid metabolismto nontoxic or less-toxic forms of the parent com-pound [3]. Many pharmacokinetic and dynamic stud-ies have elucidated that a portion of orally adminis-tered pyrethroids partition into fatty tissues, in whichthey persist for at least 3 weeks [3,22,23]. Deltamethrincan be detected in the adipose tissue of rats with ahalf-life of 5–6 days [24] and is most persistent in thebody fat of animal models [3]. The retention of thesehighly lipophilic pesticides in metabolically active adi-pose tissue should increase the spectrum of researchfrom not only neurotoxicity but to the possibility ofmetabolic effects of pyrethroid exposure, especially insusceptible populations. In this study, we showed thatdevelopmental deltamethrin affects adipogenesis andlipid homeostasis at the transcriptional level, decreas-ing the expression of some genes in the offspring ofdams exposed to 1 mg/kg every 3 days. Previous toxi-cological studies noted non–dose-dependent reductionin BW gain in adult rats and dogs following short-termexposure (0.1–10 mg/kg) and decreased fetal weightin rabbits at 16 mg/kg perinatal exposure [15]. In areproductive study on deltamethrin using rats, Abdel-Khalik et al. [25] observed a significant dose-dependentdifference (p < 0.01) in mean fetal weights and retar-dation of fetal growth at all doses tested (1, 2.5, and5 mg/kg). These observations of retarded developmentof body mass correlate to the transcriptional downreg-ulation in gene expression for the major transcriptionfactors of adipogenesis, Pparγ and Cebpα, which reg-ulate adipocyte development and maintain adipocytephenotype through regulation of downstream targetsCd36, Lpl, and Glut4. A significant downregulation ofcytokines excreted by WAT that are involved directlyin the T-cell response (Tnf, Fas/Tnf-R, Cd209e) hasa direct influence on the development of adipocytes.Decreased levels of these cytokines potentially maycontribute to an altered primary immune responseof dendritic cells (Cd209e), initiation of programmedcell-death by recruitment of caspase (Fas/Tnf-R), oralteration of macrophage Tnfα secretion, which couldimpact adipocyte differentiation and proliferation. The



expression of fatty acid uptake genes, Fabp4, Cd36, andLpl, regulated by Pparγ , was downregulated, consis-tent with an overall metabolic change in gene expres-sion for the pathway. The downregulation of Srebp1c,a transcription factor abundant in WAT that regulatesand maintains lipid homeostasis through downstreamtargets Acc-1 and Scd-1, contributes further to alter-ations in the metabolic state of WAT in the develop-ing mice. The reported nonmonotonic dose-responseof changes in gene expression cannot be explained byprevious observations or our physiological findings.

The physiological data herein describing cohortsof developmentally exposed male mice conflicts withpreviously reported toxicological observations for re-productive and developmental toxicity studies inrats, which reported significant changes in BW andWAT mass [15]. No significant difference in BWand liver weight was observed between vehicle anddeltamethrin-treated groups in multiple cohorts of 4, 5,and 11–12 months of age male mice (data not shown).However, the finding that developmental deltamethrinexposure increases locomotor activity may con-found the interpretation of potential BW changesand metabolic phenotypic changes (Richardsonet al., personal communication), which is why the sig-nificant changes in regulators of adipogenesis and lipidmetabolism at the mRNA level suggest potential un-derlying epigenetic effects.

Little is known regarding the effect of deltamethrinon glucose homeostasis, metabolic, or immuneresponse. Our data suggest that developmentaldeltamethrin exposure had no marked effect on glu-cose homeostasis based on blood glucose concentra-tions, but significant changes in the relative gene ex-pression of Glut4 and Glut2 in WAT are noted. Glut4is a major glucose transporter in WAT that if downreg-ulated will decrease the insulin-responsive uptake ofglucose into the cells, but the significant downregula-tion of Glut2 at both treatment doses, a major glucosetransporter in the liver, has the potential to affect glu-cose transport between adipose tissue, plasma, and po-tentially liver. A decrease in the glucose transport genesmay alter the deposition of glucose. Early insulin resis-tance has been linked to adipose tissue dysfunction[26], and decreased WAT expandability is associatedwith increased risk for diabetes or glucose intolerance[21, 27, 28]. Thus, deltamethrin might affect the normalresponse to high-fat diet challenge or treatment withthiazolidinedones, which promote adipogenesis to im-prove insulin resistance.

The transcriptional downregulation of genes es-sential for adipose development and lipid metabolismin offspring after perinatal exposure to 1 mg/kg dose ofdeltamethrin provides data that support the potentialfor metabolic effects of deltamethrin exposure during

development with regard to WAT expandability. Nrf2,normally known for its role in oxidative stress, has re-cently been shown to be a regulator of adipose develop-ment and function [12]. Nrf2 has been shown to be anupstream regulator of Pparγ and Cebpα, in which Nrf2knockout in MEF cells decreased lipid accumulation,decreased Pparγ and Cebpα expression at the protein,along with downstream target genes [13]. Therefore,the decreased expression of Nrf2 and its target genes atthe mRNA level can serve as initial evidence that Nrf2may be involved in the gene expression changes relatedmost specifically to the transcription factors Pparγ andCebpα, and therefore, lead to changes in glucose andlipid homeostasis. These significant changes in geneexpression at the transcriptional level may correlateto an epigenetic regulation in the offspring that mayeventually lead to altered responses of WAT to envi-ronmental toxicants (i.e., obesogens, endocrine disrup-tors) or changes in diet (i.e., high-fat diet); however,these changes did not manifest in significant alterationin physiological parameters. To summarize, perinataldeltamethrin exposure did not result in measurablechanges in BW in male offspring at 5 months of age,but did decrease the expression of some genes relatedto adipogenesis, lipogenesis, and inflammation in WATthat may potentially be under the regulation of alter-ations in Nrf2 activity.

ACKNOWEDGMENTS

Angela Baker was provided a graduate fellowshipby Bristol-Myers Squibb. Drs. Slitt, Richardson, andAleksunes are recipients of the NIEHS OutstandingNew Investigator Scientist (ONES) Award. This studyrepresents collaborative effort of these investigatorsresulting from the ONES program and is an invitedsubmission highlighting work performed by ONESrecipients.

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Effects of Developmental Deltamethrin Exposure on White Adipose Tissue Gene Expression