Journal article
The Aryl hydrocarbon receptor mediates reproductive toxicity of polychlorinated biphenyl congener 126 in rats
Toxicology and applied pharmacology, Vol.426, pp.115639-115639
09/01/2021
DOI: 10.1016/j.taap.2021.115639
PMCID: PMC8500329
PMID: 34256052
Abstract
Polychlorinated biphenyls (PCBs) are endocrine disrupting chemicals with documented, though mechanistically ill-defined, reproductive toxicity. The toxicity of dioxin-like PCBs, such as PCB126, is mediated via the aryl hydrocarbon receptor (AHR) in non-ovarian tissues. The goal of this study was to examine the uterine and ovarian effects of PCB126 and test the hypothesis that the AHR is required for PCB126-induced reproductive toxicity. Female Holzman-Sprague Dawley wild type (n = 14; WT) and Ahr knock out (n = 11; AHR−/−) rats received a single intraperitoneal injection of either corn oil vehicle (5 ml/kg: WT_O and AHR−/−_O) or PCB126 (1.63 mg/kg in corn oil: WT_PCB and AHR−/−_PCB) at four weeks of age. The estrous cycle was synchronized and ovary and uterus were collected 28 days after exposure. In WT rats, PCB126 exposure reduced (P < 0.05) body and ovary weight, uterine gland number, uterine area, progesterone, 17β-estradiol and anti-Müllerian hormone level, secondary and antral follicle and corpora lutea number but follicle stimulating hormone level increased (P < 0.05). In AHR−/− rats, PCB126 exposure increased (P ≤ 0.05) circulating luteinizing hormone level. Ovarian or uterine mRNA abundance of biotransformation, and inflammation genes were altered (P < 0.05) in WT rats due to PCB126 exposure. In AHR−/− rats, the transcriptional effects of PCB126 were restricted to reductions (P < 0.05) in three inflammatory genes. These findings support a functional role for AHR in the female reproductive tract, illustrate AHR's requirement in PCB126-induced reprotoxicity, and highlight the potential risk of dioxin-like compounds on female reproduction.
•PCB126 reduced body and ovarian weight and depleted follicles in wildtype rats.•PCB126 exposure disrupted the endocrine environment in wildtype rats.•PCB126 exposure altered chemical metabolism and inflammation mRNA level.•Lack of AHR in rats was protective against many PCB126 alterations.
Details
- Title: Subtitle
- The Aryl hydrocarbon receptor mediates reproductive toxicity of polychlorinated biphenyl congener 126 in rats
- Creators
- Violet Klenov - University of IowaSusanne Flor - University of IowaShanthi Ganesan - Iowa State UniversityMalavika Adur - Iowa State UniversityNazmin Eti - University of IowaKhursheed Iqbal - University of KansasMichael J Soares - University of KansasGabriele Ludewig - University of IowaJason W Ross - Iowa State UniversityLarry W Robertson - University of IowaAileen F Keating - Iowa State University
- Resource Type
- Journal article
- Publication Details
- Toxicology and applied pharmacology, Vol.426, pp.115639-115639
- DOI
- 10.1016/j.taap.2021.115639
- PMID
- 34256052
- PMCID
- PMC8500329
- NLM abbreviation
- Toxicol Appl Pharmacol
- ISSN
- 0041-008X
- eISSN
- 1096-0333
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 09/01/2021
- Academic Unit
- Occupational and Environmental Health; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984226820202771
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