Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure. Toxicol Sci 2023 Jun 28;194(1):84-100
Date
05/16/2023Pubmed ID
37191987Pubmed Central ID
PMC10306406DOI
10.1093/toxsci/kfad046Scopus ID
2-s2.0-85164065947 (requires institutional sign-in at Scopus site) 1 CitationAbstract
Environmental bisphenol compounds like bisphenol F (BPF) are endocrine-disrupting chemicals (EDCs) 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 10 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 suggest 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.
Author List
Wagner VA, Holl KL, Clark KC, Reho JJ, Dwinell MR, Lehmler HJ, Raff H, Grobe JL, Kwitek AEAuthors
Karen C. Clark Research Scientist I in the Physiology department at Medical College of WisconsinMelinda R. Dwinell PhD Professor in the Physiology department at Medical College of Wisconsin
Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Anne E. Kwitek PhD Professor in the Physiology department at Medical College of Wisconsin
Hershel Raff PhD Professor in the Academic Affairs department at Medical College of Wisconsin
John J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
Valerie Wagner Research Scientist I in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBenzhydryl Compounds
Endocrine Disruptors
Female
Genetic Background
Humans
Male
Rats
Rats, Inbred ACI
Rats, Inbred BUF
Rats, Inbred F344
Rats, Inbred WKY
Thyroid Gland
