Genetic background in the rat affects endocrine and metabolic outcomes of Bisphenol F exposure

Valerie A Wagner; Katie L Holl; Karen C Clark; John J Reho; Melinda R Dwinell; Hans-Joachim Lehmler; Hershel Raff; Justin L Grobe; Anne E Kwitek

doi:10.1093/toxsci/kfad046

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Genetic background in the rat affects endocrine and metabolic outcomes of Bisphenol F exposure

Valerie A Wagner, Katie L Holl, Karen C Clark, John J Reho, Melinda R Dwinell, Hans-Joachim Lehmler, Hershel Raff, Justin L Grobe and Anne E Kwitek

Toxicological sciences, Vol.194(1), pp.84-100

07/2023

DOI: 10.1093/toxsci/kfad046

PMCID: PMC10306406

PMID: 37191987

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Abstract

Environmental bisphenol compounds like bisphenol F (BPF) are endocrine disrupting chemicals (EDC) affecting adipose and classical endocrine systems. Genetic factors that influence EDC exposure outcomes are poorly understood and are unaccounted variables that may contribute to the large range of reported outcomes in the human population. We previously demonstrated that BPF exposure increased body growth and adiposity in male N/NIH Heterogeneous Stock (HS) rats, a genetically heterogeneous outbred population. We hypothesize that the founder strains of the HS rat exhibit EDC effects that were strain- and sex-dependent. Weanling littermate pairs of male and female ACI, BN, BUF, F344, M520, and WKY rats randomly received either vehicle (0.1% EtOH) or 1.125 mg BPF/L in 0.1% EtOH for ten weeks in drinking water. Body weight and fluid intake were measured weekly, metabolic parameters were assessed, and blood and tissues were collected. BPF increased thyroid weight in ACI males, thymus and kidney weight in BUF females, adrenal weight in WKY males, and possibly increased pituitary weight in BN males. BUF females also developed a disruption in activity and metabolic rate with BPF exposure. These sex- and strain-specific exposure outcomes illustrate that HS rat founders possess diverse bisphenol-exposure risk alleles and suggests that BPF exposure may intensify inherent organ system dysfunction existing in the HS rat founders. We propose that the HS rat will be an invaluable model for dissecting gene EDC interactions on health.

metabolic rate

bisphenols

environmental exposure

genetic background

Rattus norvegicus

endocrine disruptors

Details

Title: Subtitle: Genetic background in the rat affects endocrine and metabolic outcomes of Bisphenol F exposure
Creators: Valerie A Wagner - Medical College of Wisconsin
Katie L Holl - Medical College of Wisconsin
Karen C Clark - Medical College of Wisconsin
John J Reho - Medical College of Wisconsin
Melinda R Dwinell - Medical College of Wisconsin
Hans-Joachim Lehmler - University of Iowa
Hershel Raff - Medical College of Wisconsin
Justin L Grobe - Medical College of Wisconsin
Anne E Kwitek - Medical College of Wisconsin
Resource Type: Journal article
Publication Details: Toxicological sciences, Vol.194(1), pp.84-100
DOI: 10.1093/toxsci/kfad046
PMID: 37191987
PMCID: PMC10306406
NLM abbreviation: Toxicol Sci
eISSN: 1096-0929
Grant note: R24 OD024617 / NIH HHS R01 HL064541 / NHLBI NIH HHS
Language: English
Electronic publication date: 05/16/2023
Date published: 07/2023
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9984410789702771

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