PMID- 37115651
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20230702
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 194
IP  - 1
DP  - 2023 Jun 28
TI  - Fetal and neonatal dioxin exposure causes sex-specific metabolic alterations in 
      mice.
PG  - 70-83
LID - 10.1093/toxsci/kfad042 [doi]
AB  - Epidemiological studies report associations between early-life exposure to 
      persistent organic pollutants (POPs) and impaired metabolic homeostasis in 
      adulthood. We investigated the impact of early-life exposure to low-dose 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or 'dioxin') on the establishment of 
      beta-cell area during the perinatal period, as well as beta-cell health and glucose 
      homeostasis later in life. Adult female mice were injected with either corn oil 
      (CO; vehicle control) or TCDD (20 ng/kg/day) 2x/week throughout mating, 
      pregnancy, and lactation; offspring were thus indirectly exposed to maternal TCDD 
      in utero and during lactation, with pollutant exposure ending at weaning. All 
      offspring were maintained on chow diet from weaning until 12-17 weeks of age, 
      after which a subset of CO- and TCDD-exposed offspring were transferred to a 45% 
      high fat diet (HFD) as a metabolic stressor for an additional 10 weeks. TCDD 
      significantly upregulated cytochrome P450 1a1 (Cyp1a1) gene expression in 
      offspring pancreas at birth and weaning, indicating that maternal TCDD directly 
      reaches the developing pancreas. TCDD-exposed pups were transiently hypoglycemic 
      at birth and females were born with reduced % beta-cell area, which persisted into 
      adulthood. Early-life TCDD exposure had no persistent long-term effects on 
      glucose homeostasis in chow-fed offspring, but when transferred to HFD, 
      TCDD-exposed female offspring had a delayed onset of HFD-induced hyperglycemia, 
      more pronounced HFD-induced hyperinsulinemia, and increase % PCNA+ beta-cells 
      compared with CO-exposed female offspring. This study demonstrates that 
      early-life exposure of mice to TCDD has modest effects on metabolic health in 
      chow-fed offspring but alters metabolic adaptability to HFD feeding in females.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Society of Toxicology.
FAU - Hoyeck, Myriam P
AU  - Hoyeck MP
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
FAU - Merhi, Rayanna C
AU  - Merhi RC
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
FAU - Tulloch, Cameron
AU  - Tulloch C
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
FAU - McCormick, Kaitlyn
AU  - McCormick K
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
FAU - Mohammed Abu Hossain, Shahen
AU  - Mohammed Abu Hossain S
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
FAU - Hanson, Antonio A
AU  - Hanson AA
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
FAU - Bruin, Jennifer E
AU  - Bruin JE
AD  - Department of Biology, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
AD  - Institute of Biochemistry, Carleton University, Ottawa, Ontario K1S 5B6, Canada.
LA  - eng
GR  - PJT-2018-159590/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Dioxins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Pregnancy
MH  - Male
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Female
MH  - *Dioxins
MH  - *Prenatal Exposure Delayed Effects/chemically induced
MH  - *Polychlorinated Dibenzodioxins/toxicity
MH  - Reproduction
MH  - Glucose/pharmacology
PMC - PMC10306400
OTO - NOTNLM
OT  - diabetes
OT  - dioxin
OT  - early-life pollutant exposure
OT  - hypoglycemia
OT  - metabolic adaptability
OT  - beta-cell mass
EDAT- 2023/04/28 18:43
MHDA- 2023/06/30 06:42
PMCR- 2023/04/28
CRDT- 2023/04/28 12:12
PHST- 2023/06/30 06:42 [medline]
PHST- 2023/04/28 18:43 [pubmed]
PHST- 2023/04/28 12:12 [entrez]
PHST- 2023/04/28 00:00 [pmc-release]
AID - 7146505 [pii]
AID - kfad042 [pii]
AID - 10.1093/toxsci/kfad042 [doi]
PST - ppublish
SO  - Toxicol Sci. 2023 Jun 28;194(1):70-83. doi: 10.1093/toxsci/kfad042.