PMID- 28657538
OWN - NLM
STAT- MEDLINE
DCOM- 20171019
LR  - 20240327
IS  - 1552-9924 (Electronic)
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 125
IP  - 6
DP  - 2017 Jun 28
TI  - Effects of Low-Dose Developmental Bisphenol A Exposure on Metabolic Parameters 
      and Gene Expression in Male and Female Fischer 344 Rat Offspring.
PG  - 067018
LID - 10.1289/EHP505 [doi]
LID - 067018
AB  - BACKGROUND: Bisphenol A (BPA) is an endocrine-disrupting chemical that may 
      contribute to development of obesity and metabolic disorders. Humans are 
      constantly exposed to low concentrations of BPA, and studies support that the 
      developmental period is particularly sensitive. OBJECTIVES: The aim was to 
      investigate the effects of low-dose developmental BPA exposure on metabolic 
      parameters in male and female Fischer 344 (F344) rat offspring. METHODS: Pregnant 
      F344 rats were exposed to BPA via their drinking water, corresponding to 0.5 
      mug/kg BW/d (BPA0.5; <em>n</em>=21) or 50 mug/kg BW/d (BPA50; <em>n</em>=16), from 
      gestational day (GD) 3.5 until postnatal day (PND) 22, and controls were given 
      vehicle (<em>n</em>=26). Body weight (BW), adipose tissue, liver (weight, 
      histology, and gene expression), heart weight, and lipid profile were 
      investigated in the 5-wk-old offspring. RESULTS: Males and females exhibited 
      differential susceptibility to the different doses of BPA. Developmental BPA 
      exposure increased plasma triglyceride levels (0.81&plusmn;0.10 mmol/L compared 
      with 0.57&plusmn;0.03 mmol/L, females BPA50 <em>p</em>=0.04; 0.81&plusmn;0.05 
      mmol/L compared with 0.61&plusmn;0.04 mmol/L, males BPA0.5 <em>p</em>=0.005) in 
      F344 rat offspring compared with controls. BPA exposure also increased adipocyte 
      cell density by 122% in inguinal white adipose tissue (iWAT) of female offspring 
      exposed to BPA0.5 compared with controls (68.2&plusmn;4.4 number of 
      adipocytes/HPF compared with 55.9&plusmn;1.5 number of adipocytes/HPF; 
      <em>p</em>=0.03) and by 123% in BPA0.5 females compared with BPA50 animals 
      (68.2&plusmn;4.4 number of adipocytes/high power field (HPF) compared with 
      55.3&plusmn;2.9 number of adipocytes/HPF; <em>p</em>=0.04). In iWAT of male 
      offspring, adipocyte cell density was increased by 129% in BPA50-exposed animals 
      compared with BPA0.5-exposed animals (69.9&plusmn;5.1 number of adipocytes/HPF 
      compared with 54.0&plusmn;3.4 number of adipocytes/HPF; <em>p</em>=0.03). 
      Furthermore, the expression of genes involved in lipid and adipocyte homeostasis 
      was significantly different between exposed animals and controls depending on the 
      tissue, dose, and sex. CONCLUSIONS: Developmental exposure to 0.5 mug/kg BW/d of 
      BPA, which is 8-10 times lower than the current preliminary EFSA (European Food 
      Safety Authority) tolerable daily intake (TDI) of 4 mug/kg BW/d and is within the 
      range of environmentally relevant levels, was associated with sex-specific 
      differences in the expression of genes in adipose tissue plasma triglyceride 
      levels in males and adipocyte cell density in females when F344 rat offspring of 
      dams exposed to BPA at 0.5 mug/kg BW/d were compared with the offspring of 
      unexposed controls. https://doi.org/10.1289/EHP505.
FAU - Lejonklou, Margareta H
AU  - Lejonklou MH
AD  - Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala 
      University , Uppsala, Sweden.
FAU - Dunder, Linda
AU  - Dunder L
AD  - Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala 
      University , Uppsala, Sweden.
FAU - Bladin, Emelie
AU  - Bladin E
AD  - Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala 
      University , Uppsala, Sweden.
FAU - Pettersson, Vendela
AU  - Pettersson V
AD  - Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala 
      University , Uppsala, Sweden.
FAU - Ronn, Monika
AU  - Ronn M
AD  - Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala 
      University , Uppsala, Sweden.
FAU - Lind, Lars
AU  - Lind L
AD  - Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University , 
      Uppsala, Sweden.
FAU - Walden, Tomas B
AU  - Walden TB
AD  - Department of Medical Cell Biology, Uppsala University , Uppsala, Sweden.
FAU - Lind, P Monica
AU  - Lind PM
AD  - Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala 
      University , Uppsala, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170628
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Phenols)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Benzhydryl Compounds/metabolism/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Endocrine Disruptors/metabolism/*toxicity
MH  - Female
MH  - Gene Expression/drug effects
MH  - Liver/metabolism
MH  - Male
MH  - Phenols/metabolism/*toxicity
MH  - Rats
MH  - Rats, Inbred F344
PMC - PMC5743697
EDAT- 2017/06/29 06:00
MHDA- 2017/10/20 06:00
PMCR- 2017/06/28
CRDT- 2017/06/29 06:00
PHST- 2016/05/13 00:00 [received]
PHST- 2016/12/19 00:00 [revised]
PHST- 2016/12/20 00:00 [accepted]
PHST- 2017/06/29 06:00 [entrez]
PHST- 2017/06/29 06:00 [pubmed]
PHST- 2017/10/20 06:00 [medline]
PHST- 2017/06/28 00:00 [pmc-release]
AID - EHP505 [pii]
AID - 10.1289/EHP505 [doi]
PST - epublish
SO  - Environ Health Perspect. 2017 Jun 28;125(6):067018. doi: 10.1289/EHP505.