Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153
Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androsta...
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| creator | van Esterik, J.C.J. Verharen, H.W. Hodemaekers, H.M. Gremmer, E.R. Nagarajah, B. Kamstra, J.H. Dollé, M.E.T. Legler, J. van der Ven, L.T.M. |
| description | Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000pg/kgbodyweight/day; PCB 153: 0.09–1406μg/kgbodyweight/d). Then exposure was ceased and offspring were followed up to 1year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes.
•Early life exposure to TCDD affects programming of energy and immune homeostasis.•Early life exposure to PCB 153 affects programming of energy homeostasis.•Both compounds act sex-specifically.•Lowest derived BMDLs for both TCDD and PCB 153 are not lower than current tolerable daily intakes. |
| doi_str_mv | 10.1016/j.taap.2015.09.017 |
| format | Article |
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•Early life exposure to TCDD affects programming of energy and immune homeostasis.•Early life exposure to PCB 153 affects programming of energy homeostasis.•Both compounds act sex-specifically.•Lowest derived BMDLs for both TCDD and PCB 153 are not lower than current tolerable daily intakes.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2015.09.017</identifier><identifier>PMID: 26415833</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>2,3,7,8-Tetrachlorodibenzo-p-dioxin ; 60 APPLIED LIFE SCIENCES ; Adiposity - drug effects ; Age Factors ; ANDROSTANES ; Animals ; Basic Helix-Loop-Helix Transcription Factors - agonists ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Behavior, Animal - drug effects ; Biomarkers - blood ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; DIOXIN ; Dose-Response Relationship, Drug ; Endocrine disrupting compounds ; Endocrine Disruptors - toxicity ; Energy homeostasis ; Energy Metabolism - drug effects ; FATS ; Female ; Gestational Age ; GLUCAGON ; GLUCOSE ; HOMEOSTASIS ; Immune homeostasis ; Immune System - drug effects ; Immune System - immunology ; Immune System - metabolism ; Interferon-gamma - metabolism ; Interleukin-4 - metabolism ; Lactation ; Male ; Maternal Exposure ; METABOLIC DISEASES ; MICE ; Mice, Inbred C57BL ; Organ Size - drug effects ; PANCREAS ; Polychlorinated biphenyl 153 ; Polychlorinated Biphenyls - toxicity ; Polychlorinated Dibenzodioxins - toxicity ; Pregnancy ; PREGNANES ; Prenatal Exposure Delayed Effects ; PROGENY ; Programming ; RECEPTORS ; Receptors, Aryl Hydrocarbon - agonists ; Receptors, Aryl Hydrocarbon - metabolism ; Receptors, Steroid - agonists ; Receptors, Steroid - metabolism ; Sex Factors ; SPLEEN ; THYMUS ; Weight Gain - drug effects</subject><ispartof>Toxicology and applied pharmacology, 2015-12, Vol.289 (2), p.262-275</ispartof><rights>2015 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-52a346d43bdcc549c1770c0dac47fc2ea7ee1077220a0ccc2cae282c785db3c73</citedby><cites>FETCH-LOGICAL-c365t-52a346d43bdcc549c1770c0dac47fc2ea7ee1077220a0ccc2cae282c785db3c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2015.09.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26415833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22687832$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>van Esterik, J.C.J.</creatorcontrib><creatorcontrib>Verharen, H.W.</creatorcontrib><creatorcontrib>Hodemaekers, H.M.</creatorcontrib><creatorcontrib>Gremmer, E.R.</creatorcontrib><creatorcontrib>Nagarajah, B.</creatorcontrib><creatorcontrib>Kamstra, J.H.</creatorcontrib><creatorcontrib>Dollé, M.E.T.</creatorcontrib><creatorcontrib>Legler, J.</creatorcontrib><creatorcontrib>van der Ven, L.T.M.</creatorcontrib><title>Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000pg/kgbodyweight/day; PCB 153: 0.09–1406μg/kgbodyweight/d). Then exposure was ceased and offspring were followed up to 1year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes.
•Early life exposure to TCDD affects programming of energy and immune homeostasis.•Early life exposure to PCB 153 affects programming of energy homeostasis.•Both compounds act sex-specifically.•Lowest derived BMDLs for both TCDD and PCB 153 are not lower than current tolerable daily intakes.</description><subject>2,3,7,8-Tetrachlorodibenzo-p-dioxin</subject><subject>60 APPLIED LIFE SCIENCES</subject><subject>Adiposity - drug effects</subject><subject>Age Factors</subject><subject>ANDROSTANES</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - agonists</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Behavior, Animal - drug effects</subject><subject>Biomarkers - blood</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>DIOXIN</subject><subject>Dose-Response Relationship, Drug</subject><subject>Endocrine disrupting compounds</subject><subject>Endocrine Disruptors - toxicity</subject><subject>Energy homeostasis</subject><subject>Energy Metabolism - drug effects</subject><subject>FATS</subject><subject>Female</subject><subject>Gestational Age</subject><subject>GLUCAGON</subject><subject>GLUCOSE</subject><subject>HOMEOSTASIS</subject><subject>Immune homeostasis</subject><subject>Immune System - drug effects</subject><subject>Immune System - immunology</subject><subject>Immune System - metabolism</subject><subject>Interferon-gamma - metabolism</subject><subject>Interleukin-4 - metabolism</subject><subject>Lactation</subject><subject>Male</subject><subject>Maternal Exposure</subject><subject>METABOLIC DISEASES</subject><subject>MICE</subject><subject>Mice, Inbred C57BL</subject><subject>Organ Size - drug effects</subject><subject>PANCREAS</subject><subject>Polychlorinated biphenyl 153</subject><subject>Polychlorinated Biphenyls - toxicity</subject><subject>Polychlorinated Dibenzodioxins - toxicity</subject><subject>Pregnancy</subject><subject>PREGNANES</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>PROGENY</subject><subject>Programming</subject><subject>RECEPTORS</subject><subject>Receptors, Aryl Hydrocarbon - agonists</subject><subject>Receptors, Aryl Hydrocarbon - metabolism</subject><subject>Receptors, Steroid - agonists</subject><subject>Receptors, Steroid - metabolism</subject><subject>Sex Factors</subject><subject>SPLEEN</subject><subject>THYMUS</subject><subject>Weight Gain - drug effects</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAQxy0EokvhBTggS5yTju0kTiQubEpb0EpwKIib5R1Ptl5tnMjOVu1L8MwkXeDIaS7_j5n5MfZWQC5AVBf7fLJ2zCWIMocmB6GfsZWApspAKfWcrQAKkQHUP8_Yq5T2ANAUhXjJzmRViLJWasV-tUM_DsfgMm6D44kesjQS-s4jp64jnBIfAh_jsIu2733Y8aHjFCjuHp8cvu-Pgfjd0NOQJpt84j5w646HibelXm8uqi8PVz_WvPdI3HYTRT5S9MFO9sBv28vLp5hv7ZqLUr1mLzp7SPTmzzxn368-3bY32ebr9ef24yZDVZVTVkqrisoVausQy6JBoTUgOIuF7lCS1UQCtJYSLCCiREuylqjr0m0VanXO3p9y5529SegnwjscQpgPNlJWta6VnFXypMI4pBSpM2P0vY2PRoBZEJi9WRCYBYGBxswIZtO7k2k8bnty_yx_fz4LPpwENB947yku_RSQnI9LvRv8__J_Ay1bl0Y</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>van Esterik, J.C.J.</creator><creator>Verharen, H.W.</creator><creator>Hodemaekers, H.M.</creator><creator>Gremmer, E.R.</creator><creator>Nagarajah, B.</creator><creator>Kamstra, J.H.</creator><creator>Dollé, M.E.T.</creator><creator>Legler, J.</creator><creator>van der Ven, L.T.M.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>OTOTI</scope></search><sort><creationdate>20151201</creationdate><title>Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153</title><author>van Esterik, J.C.J. ; Verharen, H.W. ; Hodemaekers, H.M. ; Gremmer, E.R. ; Nagarajah, B. ; Kamstra, J.H. ; Dollé, M.E.T. ; Legler, J. ; van der Ven, L.T.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-52a346d43bdcc549c1770c0dac47fc2ea7ee1077220a0ccc2cae282c785db3c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>2,3,7,8-Tetrachlorodibenzo-p-dioxin</topic><topic>60 APPLIED LIFE SCIENCES</topic><topic>Adiposity - drug effects</topic><topic>Age Factors</topic><topic>ANDROSTANES</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - agonists</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Behavior, Animal - drug effects</topic><topic>Biomarkers - blood</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>DIOXIN</topic><topic>Dose-Response Relationship, Drug</topic><topic>Endocrine disrupting compounds</topic><topic>Endocrine Disruptors - toxicity</topic><topic>Energy homeostasis</topic><topic>Energy Metabolism - drug effects</topic><topic>FATS</topic><topic>Female</topic><topic>Gestational Age</topic><topic>GLUCAGON</topic><topic>GLUCOSE</topic><topic>HOMEOSTASIS</topic><topic>Immune homeostasis</topic><topic>Immune System - drug effects</topic><topic>Immune System - immunology</topic><topic>Immune System - metabolism</topic><topic>Interferon-gamma - metabolism</topic><topic>Interleukin-4 - metabolism</topic><topic>Lactation</topic><topic>Male</topic><topic>Maternal Exposure</topic><topic>METABOLIC DISEASES</topic><topic>MICE</topic><topic>Mice, Inbred C57BL</topic><topic>Organ Size - drug effects</topic><topic>PANCREAS</topic><topic>Polychlorinated biphenyl 153</topic><topic>Polychlorinated Biphenyls - toxicity</topic><topic>Polychlorinated Dibenzodioxins - toxicity</topic><topic>Pregnancy</topic><topic>PREGNANES</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>PROGENY</topic><topic>Programming</topic><topic>RECEPTORS</topic><topic>Receptors, Aryl Hydrocarbon - agonists</topic><topic>Receptors, Aryl Hydrocarbon - metabolism</topic><topic>Receptors, Steroid - agonists</topic><topic>Receptors, Steroid - metabolism</topic><topic>Sex Factors</topic><topic>SPLEEN</topic><topic>THYMUS</topic><topic>Weight Gain - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Esterik, J.C.J.</creatorcontrib><creatorcontrib>Verharen, H.W.</creatorcontrib><creatorcontrib>Hodemaekers, H.M.</creatorcontrib><creatorcontrib>Gremmer, E.R.</creatorcontrib><creatorcontrib>Nagarajah, B.</creatorcontrib><creatorcontrib>Kamstra, J.H.</creatorcontrib><creatorcontrib>Dollé, M.E.T.</creatorcontrib><creatorcontrib>Legler, J.</creatorcontrib><creatorcontrib>van der Ven, L.T.M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van Esterik, J.C.J.</au><au>Verharen, H.W.</au><au>Hodemaekers, H.M.</au><au>Gremmer, E.R.</au><au>Nagarajah, B.</au><au>Kamstra, J.H.</au><au>Dollé, M.E.T.</au><au>Legler, J.</au><au>van der Ven, L.T.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>289</volume><issue>2</issue><spage>262</spage><epage>275</epage><pages>262-275</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><abstract>Early life exposure to endocrine disrupting compounds has been linked to chronic diseases later in life, like obesity and related metabolic disorders. We exposed C57BL/6JxFVB hybrid mice to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the constitutive androstane receptor/pregnane X receptor agonist polychlorinated biphenyl 153 (PCB 153) in an experimental design relevant for human exposure. Exposure occurred during gestation and lactation via maternal feed to a wide dose range (TCDD: 10–10,000pg/kgbodyweight/day; PCB 153: 0.09–1406μg/kgbodyweight/d). Then exposure was ceased and offspring were followed up to 1year of age. Metabolic parameters like body weight, fat pad weights, glucose tolerance, endocrine serum profile, and neurobehavioral and immunological parameters were determined. Body weight was transiently affected by both compounds throughout the follow-up. TCDD-exposed males showed decreased fat pad and spleen weights and an increase in IL-4 production of splenic immune cells. In contrast, females showed increased fat pad weights and production of IFNγ. PCB 153-exposed males showed an increase in glucose, whereas females showed an increase in glucagon, a decrease in pancreas weight, and an increase in thymus weight. In conclusion, early life exposure to TCDD appears to affect programming of energy and immune homeostasis in offspring, whereas the effects of perinatal PCB 153 were mainly on programming of glucose homeostasis. Both compounds act sex-specifically. Lowest derived BMDLs (lower bounds of the (two sided) 90%-confidence interval for the benchmark dose) for both compounds are not lower than current tolerable daily intakes.
•Early life exposure to TCDD affects programming of energy and immune homeostasis.•Early life exposure to PCB 153 affects programming of energy homeostasis.•Both compounds act sex-specifically.•Lowest derived BMDLs for both TCDD and PCB 153 are not lower than current tolerable daily intakes.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26415833</pmid><doi>10.1016/j.taap.2015.09.017</doi><tpages>14</tpages></addata></record> |
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| ispartof | Toxicology and applied pharmacology, 2015-12, Vol.289 (2), p.262-275 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 2,3,7,8-Tetrachlorodibenzo-p-dioxin 60 APPLIED LIFE SCIENCES Adiposity - drug effects Age Factors ANDROSTANES Animals Basic Helix-Loop-Helix Transcription Factors - agonists Basic Helix-Loop-Helix Transcription Factors - metabolism Behavior, Animal - drug effects Biomarkers - blood Blood Glucose - drug effects Blood Glucose - metabolism DIOXIN Dose-Response Relationship, Drug Endocrine disrupting compounds Endocrine Disruptors - toxicity Energy homeostasis Energy Metabolism - drug effects FATS Female Gestational Age GLUCAGON GLUCOSE HOMEOSTASIS Immune homeostasis Immune System - drug effects Immune System - immunology Immune System - metabolism Interferon-gamma - metabolism Interleukin-4 - metabolism Lactation Male Maternal Exposure METABOLIC DISEASES MICE Mice, Inbred C57BL Organ Size - drug effects PANCREAS Polychlorinated biphenyl 153 Polychlorinated Biphenyls - toxicity Polychlorinated Dibenzodioxins - toxicity Pregnancy PREGNANES Prenatal Exposure Delayed Effects PROGENY Programming RECEPTORS Receptors, Aryl Hydrocarbon - agonists Receptors, Aryl Hydrocarbon - metabolism Receptors, Steroid - agonists Receptors, Steroid - metabolism Sex Factors SPLEEN THYMUS Weight Gain - drug effects |
| title | Compound- and sex-specific effects on programming of energy and immune homeostasis in adult C57BL/6JxFVB mice after perinatal TCDD and PCB 153 |
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