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Am J Obstet Gynecol. 2017 Mar;216(3):290.e1-290.e9. doi: 10.1016/j.ajog.2016.08.041. Epub 2016 Nov 9.

Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance.

Author information

1
Perinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA.
2
Perinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA.
3
Perinatal Research Laboratory, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Department of Obstetrics and Gynecology, Torrance, CA; Department of Biological Sciences, California State Polytechnic University, Pomona, CA. Electronic address: jkjellyman@cpp.edu.

Abstract

BACKGROUND:

The obesogenic and diabetogenic effects of the environmental toxin bisphenol A during critical windows of development are well recognized. Liver and skeletal muscle play a central role in the control of glucose production, utilization, and storage.

OBJECTIVES:

We hypothesized that maternal bisphenol A exposure disrupts insulin signaling in rat offspring liver and skeletal muscle. We determined the protein expression of hepatic and skeletal muscle insulin signaling molecules including insulin receptor beta, its downstream target insulin receptor substrate 1 and glucose transporters (glucose transporter 2, glucose transporter 4), and hepatic glucose-regulating enzymes phosphoenolpyruvate carboxykinase and glucokinase.

STUDY DESIGN:

Rat dams had ad libitum access to filtered drinking water (control) or drinking water with bisphenol A from 2 weeks prior to mating and through pregnancy and lactation. Offspring litters were standardized to 4 males and 4 females and nursed by the same dam. At weaning, bisphenol A exposure was removed from all offspring. Glucose tolerance was tested at 6 weeks and 6 months. Liver and skeletal muscle was collected from 3 week old and 10 month old offspring for protein expression (Western blot) of insulin receptor beta, insulin receptor substrate 1, glucose transporter 2, glucose transporter 4, phosphoenolpyruvate carboxykinase, and glucokinase.

RESULTS:

Male, but not female, bisphenol A offspring had impaired glucose tolerance at 6 weeks and 6 months. Both male and female adult offspring had higher glucose-stimulated insulin secretion as well as the ratio of stimulated insulin to glucose. Male bisphenol A offspring had higher liver protein abundance of the 200 kDa insulin receptor beta precursor (2-fold), and insulin receptor substrate 1 (1.5-fold), whereas glucose transporter 2 was 0.5-fold of the control at 3 weeks of age. In adult male bisphenol A offspring, the abundance of insulin receptor beta was higher (2-fold) and glucose transporter 4 was 0.8-fold of the control in skeletal muscle. In adult female bisphenol A offspring, the skeletal muscle protein abundance of glucose transporter 4 was 0.4-fold of the control.

CONCLUSION:

Maternal bisphenol A had sex- and tissue-specific effects on insulin signaling components, which may contribute to increased risk of glucose intolerance in offspring. Glucose transporters were consistently altered at both ages as well as in both sexes and may contribute to glucose intolerance. These data suggest that maternal bisphenol A exposure should be limited during pregnancy and lactation.

KEYWORDS:

bisphenol A; fetal programming; glucose transporter 4; insulin signaling; rat

PMID:
27836638
PMCID:
PMC5483456
DOI:
10.1016/j.ajog.2016.08.041
[Indexed for MEDLINE]
Free PMC Article

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