Persistent autism-relevant behavioral phenotype and social neuropeptide alterations in female mice offspring induced by maternal transfer of PBDE congeners in the commercial mixture DE-71

Elena V. Kozlova, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Matthew C. Valdez, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Maximillian E. Denys, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Anthony E. Bishay, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Julia M. Krum, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Kayhon M. Rabbani, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Valeria Carrillo, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Gwendolyn M. Gonzalez, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Gregory Lampel, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Jasmin D. Tran, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Brigitte M. Vazquez, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Laura M. Anchondo, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Syed A. Uddin, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Nicole M. Huffman, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Eduardo Monarrez, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Duraan S. Olomi, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Bhuvaneswari D. Chinthirla, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.
Richard E. Hartman, Department of Psychology, Loma Linda University, Loma Linda, CA, 92350, USA.Follow
Prasada Rao Kodavanti, Neurological and Endocrine Toxicology Branch, Public Health and Integrated Toxicology Division, CPHEA/ORD, U.S. Environmental Protection Agency, Research Triangle Park, Durham, NC, 27711, USA.
Gladys Chompre, Biotechnology Department, Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico, 00717-9997, USA.
Allison L. Phillips, Duke University, Nicholas School of the Environment, Durham, NC, 27710, USA.
Heather M. Stapleton, Duke University, Nicholas School of the Environment, Durham, NC, 27710, USA.
Bernhard Henkelmann, Helmholtz Zentrum Munchen, Molecular EXposomics (MEX), German National Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, Neuherberg, Munich, Germany.
Karl-Werner Schramm, Helmholtz Zentrum Munchen, Molecular EXposomics (MEX), German National Research Center for Environmental Health (GmbH), Ingolstaedter Landstrasse 1, Neuherberg, Munich, Germany.
Margarita C. Curras-Collazo, Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA.Follow

Document Type

Article

Publication Date

10-23-2021

Publication Title

Archives of toxicology

E-ISSN

1432-0738

Abstract

Polybrominated diphenyl ethers (PBDEs) are ubiquitous persistent organic pollutants (POPs) that are known neuroendocrine disrupting chemicals with adverse neurodevelopmental effects. PBDEs may act as risk factors for autism spectrum disorders (ASD), characterized by abnormal psychosocial functioning, although direct evidence is currently lacking. Using a translational exposure model, we tested the hypothesis that maternal transfer of a commercial mixture of PBDEs, DE-71, produces ASD-relevant behavioral and neurochemical deficits in female offspring. C57Bl6/N mouse dams (F0) were exposed to DE-71 via oral administration of 0 (VEH/CON), 0.1 (L-DE-71) or 0.4 (H-DE-71) mg/kg bw/d from 3 wk prior to gestation through end of lactation. Mass spectrometry analysis indicated in utero and lactational transfer of PBDEs (in ppb) to F1 female offspring brain tissue at postnatal day (PND) 15 which was reduced by PND 110. Neurobehavioral testing of social novelty preference (SNP) and social recognition memory (SRM) revealed that adult L-DE-71 F1 offspring display deficient short- and long-term SRM, in the absence of reduced sociability, and increased repetitive behavior. These effects were concomitant with reduced olfactory discrimination of social odors. Additionally, L-DE-71 exposure also altered short-term novel object recognition memory but not anxiety or depressive-like behavior. Moreover, F1 L-DE-71 displayed downregulated mRNA transcripts for oxytocin (Oxt) in the bed nucleus of the stria terminalis (BNST) and supraoptic nucleus, and vasopressin (Avp) in the BNST and upregulated Avp1ar in BNST, and Oxtr in the paraventricular nucleus. Our work demonstrates that developmental PBDE exposure produces ASD-relevant neurochemical, olfactory processing and behavioral phenotypes that may result from early neurodevelopmental reprogramming within central social and memory networks.

DOI

10.1007/s00204-021-03163-4

PubMed ID

34687351

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