Preconceptional, Gestational, and Lactational Exposure to an Unconventional Oil and Gas Chemical Mixture Alters Energy Expenditure in Adult Female Mice

Abstract

Previous studies conducted in our laboratory have found altered adult health outcomes in animals with prenatal exposure to environmentally relevant levels of unconventional oil and gas (UOG) chemicals with endocrine-disrupting activity. This study aimed to examine potential metabolic health outcomes following a preconception, prenatal and postnatal exposure to a mixture of 23 UOG chemicals. Prior to mating and from gestation day 1 to postnatal day 21, C57BL/6J mice were developmentally exposed to a laboratory-created mixture of 23 UOG chemicals in maternal drinking water. Body composition, spontaneous activity, energy expenditure, and glucose tolerance were evaluated in 7-month-old female offspring. Neither body weight nor body composition differed in 7-month female mice. However, females exposed to 1.5 and 150 μg/kg/day UOG mix had lower total and resting energy expenditure within the dark cycle. In the light cycle, the 1,500 μg//kg/day group had lower total energy expenditure and the 1.5 μg/kg/day group had lower resting energy expenditure. Females exposed to the 150 μg/kg/day group had lower spontaneous activity in the dark cycle, and females exposed to the 1,500 μg/kg/day group had lower activity in the light cycle. This study reports for the first time that developmental exposure to a mixture of 23 UOG chemicals alters energy expenditure and spontaneous activity in adult female mice.

Keywords: developmental origins of health and disease; endocrine disrupting chemicals; energy expenditure; hydraulic fracturing; metabolic disruptors; metabolism; unconventional oil and gas.

Figure 1

Experimental timeline. Dams (n = 14, 9, 11, 8, and 10) that were exposed to the 23 UOG chemical mixture (at concentrations of 0, 0.01, 0.10, 1.0, or 10 μg/mL, respectively) for 5 weeks prior to mating. Chemical exposure was paused while females were mated in order to bypass the window of fertilization, and to avoid consumption of treatment chemicals by the males. Treatment was resumed at gestational day 1 (1 day after presence of copulatory plug) and continued through weaning of the F1 generation at PND 21. Body composition was measured at PND 7, PND 21, and at 7 months of age. Energy balance analyses including energy expenditure, activity, food intake, and glucose tolerance were measured at 7 months of age.

Figure 2

Body weights of offspring. Estimated marginal means (±) SEM of body weight at post-natal day 7 (A), post-natal day 21 (B), and at 7 months of age (C). *p < 0.05 relative to vehicle **p < 0.0125 relative to vehicle (n = 9, 11, 9, 10, 10 respectively for vehicle, 1.5, 15, 150, and 1,500 μg/kg/day treatment groups). Models included covariates: litter, date body weight was taken and litter size.

Figure 3

Energy Expenditure in Female Offspring at 7 months of age. Estimated marginal means (±) SEM in 12-h average increments of total energy expenditure (A), resting energy expenditure (B), non-resting expenditure (C) (n = 7, 4, 6, 6, 5 respectively for vehicle, 1.5, 15, 150, and 1,500 μg/kg/day treatment groups). *p < 0.05 relative to vehicle **p < 0.0125 relative to vehicle. Models included covariates: litter, date of recording, litter size, and body weight.

Figure 4

Activity of female offspring at 7 months of age. Estimated marginal means (±) SEM in 12-h average increments of total spontaneous activity (A), and meters travelled (B) (n = 7, 4, 6, 6, 5 respectively for vehicle, 1.5, 15, 150, and 1,500 μg/kg/day treatment groups). *p < 0.05 relative to vehicle. Models included covariates: litter and date of recording.

Figure 5

Food consumption in female offspring at 7 months of age. Estimated marginal means (±) SEM of food intake at 7 months of age in 12 h increments of both light and dark cycle (n = 7, 4, 6, 6, 5 respectively for vehicle, 1.5, 15, 150, and 1,500 μg/kg/day treatment groups). *p < 0.05 relative to vehicle. Models included date of recording as a covariate.