Transcriptomic analysis of effects of developmental PCB exposure in the hypothalamus of female rats
- PMID: 39798907
- PMCID: PMC12054745
- DOI: 10.1016/j.mce.2025.112460
Transcriptomic analysis of effects of developmental PCB exposure in the hypothalamus of female rats
Abstract
This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these latter phenotypes. We used 3' targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.
Keywords: Anteroventral periventricular nucleus (AVPV); Arcuate nucleus (ARC); Aroclor 1221; Endocrine-disrupting chemical (EDC); PCB; Transcriptomics.
Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrea C Gore reports financial support was provided by National Institute of Environmental Health Sciences. Andrea C Gore reports a relationship with Endocrine Society that includes: board membership. Andrea C Gore reports a relationship with Friedman Rubin LLC that includes: paid expert testimony. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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