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Longitudinal Metabolic Impacts of Perinatal Exposure to Phthalates and Phthalate
Mixtures in Mice.
Authors Neier K, Cheatham D, Bedrosian LD, Gregg BE, Song PXK, Dolinoy DC
Submitted By Submitted Externally on 8/6/2019
Status Published
Journal Endocrinology
Year 2019
Date Published 7/1/2019
Volume : Pages 160 : 1613 - 1630
PubMed Reference 31125050
Abstract Developmental exposures to phthalates are suspected to contribute to risk of
metabolic syndrome. However, findings from human studies are inconsistent, and
long-term metabolic impacts of early-life phthalate and phthalate mixture
exposures are not fully understood. Furthermore, most animal studies
investigating metabolic impacts of developmental phthalate exposures have
focused on diethylhexyl phthalate (DEHP), whereas newer phthalates, such as
diisononyl phthalate (DINP), are understudied. We used a longitudinal mouse
model to evaluate long-term metabolic impacts of perinatal exposures to three
individual phthalates, DEHP, DINP, and dibutyl phthalate (DBP), as well as two
mixtures (DEHP+DINP and DEHP+DINP+DBP). Phthalates were administered to pregnant
and lactating females through phytoestrogen-free chow at the following exposure
levels: 25 mg of DEHP/kg of chow, 25 mg of DBP/kg of chow, and 75 mg of DINP/kg
of chow. One male and female per litter (n = 9 to 13 per sex per group) were
weaned onto control chow and followed until 10 months of age. They underwent
metabolic phenotyping at 2 and 8 months, and adipokines were measured in plasma
collected at 10 months. Longitudinally, females perinatally exposed to DEHP only
had increased body fat percentage and decreased lean mass percentage, whereas
females perinatally exposed to DINP only had impaired glucose tolerance.
Perinatal phthalate exposures also modified the relationship between body fat
percentage and plasma adipokine levels at 10 months in females.
Phthalate-exposed males did not exhibit statistically significant differences in
the measured longitudinal metabolic outcomes. Surprisingly, perinatal phthalate
mixture exposures were statistically significantly associated with few metabolic
effects and were not associated with larger effects than single exposures,
revealing complexities in metabolic effects of developmental phthalate mixture


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