Environmental Endocrine Disruptor Affects Voluntary Physical Activity in Mice

Abstract

INTRODUCTION Voluntary physical activity levels are regulated by sex hormones. The purpose of this study was to determine the effect of the endocrine disruptor benzyl butyl phthalate (BBP) on the regulation of physical activity in mice. METHODS Mouse dams were treated with 500 mg·kg−1·day−1 of BBP or vehicle on gestation days 9–16. Pups were weaned and analyzed for voluntary physical activity levels, puberty development, sex hormone levels, and body composition over a 20 week period. RESULTS Seventy-three offspring from BBP treated dams were studied (n=43 males, n=30 females). Endocrine disruption was indicated by decreased anogenital distances in BBP-treated male offspring at 10 (p=0.001) and 20 weeks (p=0.038) and delayed vaginal openings in BBP-treated female offspring (p=0.001). Further, there was a significant decrease in serum testosterone concentration in male mice between control and BBP at 10 weeks (p=0.039) and at 20 weeks (p=0.022). In female mice there was a significant increase in serum testosterone concentration in BBP mice at 20 weeks (p=0.002), and a significant increase in estrogen (estradiol) concentrations at 20 weeks in the control female mice (p=0.015). Overall, BBP mice ran significantly less distance (males, p=0.008; females, p=0.042) than controls. Other than a significant increase in BBP-treated males in fat mass at 20 weeks (p=0.040), there was no significant decrease in weight, lean mass, or fat mass in either female or male mice, regardless of treatment. CONCLUSION Maternal endocrine disruption altered hormone response, but not body composition in either sex of offspring, with a corresponding decreased activity throughout early adulthood in all offspring. These results suggest that exposure to common environmental endocrine disruptors in utero, can reduce and alter physical activity levels in offspring.

High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

“…We hypothesized that chronic overfeeding would significantly reduce the sex hormone levels in male (testosterone) and female (17β-estradiol) mice, and that exogenous sex hormone supplementation would demonstrate the sex hormones and mediators between overfeeding and reduced wheel running activity. Determining whether a causal link between chronic overfeeding and physical inactivity exists would support the hypothesis that environmental factors can directly influence the biological mechanisms controlling daily activity as recently suggested by Schmitt et al ( 2016 ).…”

“…While the biological regulation of physical activity is strongly influenced by the primary sex hormones, few studies have tested whether a factor(s) known to disrupt the levels of the sex hormones could have a direct effect on activity levels. To date, the only study to our knowledge which has tested such a link, is a recent study from our lab by Schmitt et al ( 2016 ), which demonstrated that disruption to the levels of testosterone and 17β-estradiol by a common environmental endocrine disruptor benzylbutylphthalate (BBP), decreased wheel running in mice. Thus, physical activity can be inhibited by exposure(s) that disrupt the levels of the primary sex hormones.…”

Biological/Genetic Regulation of Physical Activity Level

“…serotonin pathways, 146), or simply due to alterations in substrate availability for activity (102). Additionally, early-life exposure to unique environmental toxicants, such as a common plasticizer (BBP), may inhibit lifelong activity in offspring through alterations in sex hormone levels or other biological mechanisms when their mothers are exposed to physiologically relevant doses during pregnancy (147). Also, it has been suggested that maternal diet (148) or exercise in and of itself may affect the activity level of the offspring (149, 150).…”

Urinary BPA and Phthalate Metabolite Concentrations and Plasma Vitamin D Levels in Pregnant Women: A Repeated Measures Analysis

“…It is also possible that certain lifestyle or physiological factors may partially mediate the associations observed in our study. For example, although studies investigating the relationships between phthalate and BPA exposure and physical activity are lacking, recent animal studies suggest that exposure to endocrine-disrupting chemicals such as phthalates and BPA may reduce or alter voluntary physical activity in mice ( Johnson et al 2015 ; Schmitt et al 2016 ). Because physical activity has been positively associated with 25(OH)D concentrations in pregnant women ( Moon et al 2015 ; Woolcott et al 2016 ), physical activity may be one possible mechanism through which maternal phthalate and/or BPA exposure might contribute to decreased concentrations of 25(OH)D. In the current study, we did not collect data on physical activity from our participants.…”