Prenatal benzene exposure in mice alters offspring hypothalamic development predisposing to metabolic disease in later life.
Air pollution
Hypothalamic development
Metabolic programming
Metabolic syndrome
Neuroinflammation
Prenatal exposures
Journal
Chemosphere
ISSN: 1879-1298
Titre abrégé: Chemosphere
Pays: England
ID NLM: 0320657
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
01
02
2023
revised:
10
04
2023
accepted:
18
04
2023
pmc-release:
01
07
2024
medline:
15
5
2023
pubmed:
22
4
2023
entrez:
21
04
2023
Statut:
ppublish
Résumé
Maternal exposure to environmental contaminants during pregnancy poses a significant threat to a developing fetus, as these substances can easily cross the placenta and disrupt the neurodevelopment of offspring. Specifically, the hypothalamus is essential in the regulation of metabolism, notably during critical windows of development. An abnormal hormonal and inflammatory milieu during development can trigger persistent changes in the function of hypothalamic circuits, leading to long-lasting effects on the body's energy homeostasis and metabolism. We recently demonstrated that gestational exposure to clinically relevant levels of benzene induces severe metabolic dysregulation in the offspring. Given the central role of the hypothalamus in metabolic control, we hypothesized that prenatal exposure to benzene impacts hypothalamic development, contributing to the adverse metabolic effects in the offspring. C57BL/6JB dams were exposed to benzene at 50 ppm in the inhalation chambers exclusively during pregnancy (from E0.5 to E19). Transcriptomic analysis of the exposed offspring at postnatal day 21 (P21) revealed hypothalamic changes in genes related to metabolic regulation, inflammation, and neurodevelopment exclusively in males. Moreover, the hypothalamus of prenatally benzene-exposed male offspring displayed alterations in orexigenic and anorexigenic projections, impairments in leptin signaling, and increased microgliosis. Additional exposure to benzene during lactation did not promote further microgliosis or astrogliosis in the offspring, while the high-fat diet (HFD) challenge in adulthood exacerbated glucose metabolism and hypothalamic inflammation in benzene-exposed offspring of both sexes. These findings reveal the persistent adverse effects of prenatal benzene exposure on hypothalamic circuits and neuroinflammation, predisposing the offspring to long-lasting metabolic health conditions.
Identifiants
pubmed: 37084897
pii: S0045-6535(23)01005-6
doi: 10.1016/j.chemosphere.2023.138738
pmc: PMC10199724
mid: NIHMS1896549
pii:
doi:
Substances chimiques
Benzene
J64922108F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
138738Subventions
Organisme : NIEHS NIH HHS
ID : P42 ES030991
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES033171
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL120822
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM142519
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES020957
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Curr Biol. 2007 Sep 18;17(18):1586-94
pubmed: 17825558
Nature. 2017 Jan 26;541(7638):481-487
pubmed: 28099414
Bioinformatics. 2019 Jun 1;35(12):2084-2092
pubmed: 30395178
J Neurosci. 2012 Jan 25;32(4):1244-52
pubmed: 22279209
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Biol Psychiatry. 2016 Sep 15;80(6):479-489
pubmed: 27133954
Mol Metab. 2018 Sep;15:1-2
pubmed: 30032908
Birth Defects Res. 2019 Oct 15;111(17):1259-1269
pubmed: 31313499
Neurotoxicology. 2012 Oct;33(5):972-84
pubmed: 22981845
J Hum Cap. 2011 Summer;5(2):207-254
pubmed: 22272363
Nat Commun. 2017 Feb 22;8:14556
pubmed: 28223698
Cell Rep. 2022 Feb 1;38(5):110310
pubmed: 35108542
Diabetologia. 2010 Mar;53(3):525-35
pubmed: 19902173
Front Endocrinol (Lausanne). 2022 Jul 13;13:937281
pubmed: 35909554
Reprod Toxicol. 2011 Apr;31(3):363-73
pubmed: 21256208
Front Neurosci. 2019 Nov 21;13:1232
pubmed: 31824243
Nat Neurosci. 2016 Mar;19(3):504-16
pubmed: 26780511
J Vis Exp. 2018 Jun 5;(136):
pubmed: 29939190
Cell Metab. 2008 Feb;7(2):179-85
pubmed: 18249177
Front Endocrinol (Lausanne). 2022 Aug 08;13:950105
pubmed: 36004354
Trends Pharmacol Sci. 2016 Feb;37(2):101-113
pubmed: 26719217
Int J Epidemiol. 2016 Feb;45(1):160-9
pubmed: 26748845
J Cereb Blood Flow Metab. 2014 Feb;34(2):339-46
pubmed: 24301293
PLoS One. 2009 Jul 16;4(7):e6259
pubmed: 19606226
Hum Mol Genet. 2015 Aug 1;24(15):4327-39
pubmed: 25954031
Nicotine Tob Res. 2016 Sep;18(9):1886-94
pubmed: 27113015
Eur J Hum Genet. 2016 Jun;24(6):944-8
pubmed: 26508570
Diabetes. 2002 Apr;51(4):1233-9
pubmed: 11916950
Genome Biol. 2014;15(12):550
pubmed: 25516281
Cell Mol Life Sci. 2015 Aug;72(15):2911-28
pubmed: 26084873
Dis Model Mech. 2017 Jun 1;10(6):679-689
pubmed: 28592656
Front Neuroendocrinol. 2019 Jan;52:156-164
pubmed: 30481522
Transl Psychiatry. 2022 Dec 8;12(1):507
pubmed: 36481769
Cardiovasc Diabetol. 2022 Sep 3;21(1):174
pubmed: 36057662
CNS Neurosci Ther. 2021 Jan;27(1):36-47
pubmed: 33381913
Diabetes Care. 2014 Nov;37(11):2966-73
pubmed: 25092685
Development. 2003 Jan;130(2):401-10
pubmed: 12466206
Nat Metab. 2021 Mar;3(3):428-441
pubmed: 33758424
J Neurotrauma. 2020 Feb 1;37(3):528-533
pubmed: 31354034
Front Cell Neurosci. 2017 Mar 17;11:69
pubmed: 28367116
Front Immunol. 2021 Mar 15;12:630318
pubmed: 33790902
Ann Glob Health. 2018 Jul 27;84(2):225-238
pubmed: 30873816
Environ Sci Technol. 2015 May 5;49(9):5261-76
pubmed: 25873211
Front Neurosci. 2014 Oct 13;8:313
pubmed: 25352770
Nutr Metab (Lond). 2021 Apr 13;18(1):39
pubmed: 33849593
Am J Epidemiol. 2019 Feb 1;188(2):389-397
pubmed: 30452528
Mol Metab. 2017 Mar 16;6(5):393-405
pubmed: 28462074
Med Hypotheses. 2006;67(2):307-10
pubmed: 16616435
iScience. 2023 Feb 27;26(4):106287
pubmed: 37153445
PLoS One. 2011;6(7):e21800
pubmed: 21789182
Endocrinology. 2010 Oct;151(10):4756-64
pubmed: 20685869
Best Pract Res Clin Endocrinol Metab. 2014 Oct;28(5):757-64
pubmed: 25256770
Brain Behav Immun. 2020 Oct;89:87-99
pubmed: 32505715
Cell Metab. 2019 Nov 5;30(5):952-962.e5
pubmed: 31495690
Glia. 2020 Jun;68(6):1085-1099
pubmed: 31743527
Cell. 2014 Jan 30;156(3):495-509
pubmed: 24462248
Toxicol Sci. 2021 Apr 12;180(2):252-261
pubmed: 33502539
Curr Opin Neurobiol. 2017 Dec;47:146-155
pubmed: 29096243
Neurochem Int. 2020 Jun;136:104715
pubmed: 32169588
Nat Neurosci. 2014 Apr;17(4):549-58
pubmed: 24584052
Biochem Biophys Res Commun. 2007 Jul 27;359(2):239-44
pubmed: 17543283
Bioinformatics. 2013 Jul 15;29(14):1830-1
pubmed: 23740750
Front Immunol. 2019 Jun 06;10:1299
pubmed: 31244845
Neural Dev. 2019 Jan 18;14(1):2
pubmed: 30658714
J Neuroinflammation. 2017 May 5;14(1):99
pubmed: 28476157
Physiol Rep. 2015 Apr;3(4):
pubmed: 25907790
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Environ Health Perspect. 2013 Feb;121(2):170-80
pubmed: 23232494
J Transl Med. 2015 Oct 15;13:327
pubmed: 26472248
JCI Insight. 2018 Sep 6;3(17):
pubmed: 30185666
Brain Behav Immun. 2014 Mar;37:30-44
pubmed: 24184474
Diabetes Care. 2022 Jul 7;45(7):1621-1630
pubmed: 35607770
Int J Dev Neurosci. 2016 Oct;53:18-25
pubmed: 27326907
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
FASEB J. 2012 Nov;26(11):4743-54
pubmed: 22815382
Pediatr Obes. 2021 Jul;16(7):e12763
pubmed: 33381912
PLoS One. 2017 Mar 08;12(3):e0173055
pubmed: 28273096
Am J Physiol Endocrinol Metab. 2018 Jul 1;315(1):E72-E80
pubmed: 29351483
J Clin Psychopharmacol. 2013 Jun;33(3):313-8
pubmed: 23609384
PLoS Genet. 2014 Sep 25;10(9):e1004642
pubmed: 25255445
Diabetes. 1988 Sep;37(9):1163-7
pubmed: 3044882
J Clin Invest. 2008 Jun;118(6):2347-64
pubmed: 18497885
Am J Physiol Endocrinol Metab. 2014 Jun 1;306(11):E1305-14
pubmed: 24735888
Endocrinology. 2007 Dec;148(12):6073-82
pubmed: 17872366
Exp Mol Med. 2021 Jul;53(7):1109-1115
pubmed: 34211092
BMC Public Health. 2022 Oct 14;22(1):1917
pubmed: 36242012
J Reprod Immunol. 2021 Jun;145:103305
pubmed: 33725526
Diabetologia. 2013 May;56(5):1129-39
pubmed: 23423668
Cell Metab. 2012 May 2;15(5):703-12
pubmed: 22560222
Exp Neurol. 1973 Oct;41(1):163-73
pubmed: 4743483
BMC Med Genet. 2013 Jan 29;14:19
pubmed: 23356586
Curr Biol. 2017 Aug 21;27(16):2486-2498.e6
pubmed: 28781053
J Autoimmun. 2019 Dec;105:102300
pubmed: 31296356
J Comp Neurol. 2001 Dec 24;441(4):302-23
pubmed: 11745652
J Med Genet. 2019 May;56(5):332-339
pubmed: 30487245
Endocrinology. 2010 Sep;151(9):4270-9
pubmed: 20668022
Pediatr Res. 1976 Jul;10(7):696-701
pubmed: 934736
BMC Genet. 2010 Apr 23;11:26
pubmed: 20416077
Environ Res. 2021 Sep;200:111690
pubmed: 34273365
Animal Model Exp Med. 2019 Sep 25;2(4):252-258
pubmed: 31942557
Int J Environ Res Public Health. 2016 Oct 31;13(11):
pubmed: 27809262
PLoS One. 2013 May 02;8(5):e63549
pubmed: 23658839