Sex-dependent effects of developmental exposure to bisphenol A and ethinyl estradiol on metabolic parameters and voluntary physical activity

Abstract

Endocrine disrupting chemicals (EDC) have received considerable attention as potential obesogens. Past studies examining obesogenic potential of one widespread EDC, bisphenol A (BPA), have generally focused on metabolic and adipose tissue effects. However, physical inactivity has been proposed to be a leading cause of obesity. A paucity of studies has considered whether EDC, including BPA, affects this behavior. To test whether early exposure to BPA and ethinyl estradiol (EE, estrogen present in birth control pills) results in metabolic and such behavioral disruptions, California mice developmentally exposed to BPA and EE were tested as adults for energy expenditure (indirect calorimetry), body composition (echoMRI) and physical activity (measured by beam breaks and voluntary wheel running). Serum glucose and metabolic hormones were measured. No differences in body weight or food consumption were detected. BPA-exposed females exhibited greater variation in weight than females in control and EE groups. During the dark and light cycles, BPA females exhibited a higher average respiratory quotient than control females, indicative of metabolizing carbohydrates rather than fats. Various assessments of voluntary physical activity in the home cage confirmed that during the dark cycle, BPA and EE-exposed females were significantly less active in this setting than control females. Similar effects were not observed in BPA or EE-exposed males. No significant differences were detected in serum glucose, insulin, adiponectin and leptin concentrations. Results suggest that females developmentally exposed to BPA exhibit decreased motivation to engage in voluntary physical activity and altered metabolism of carbohydrates v. fats, which could have important health implications.

Sex‐dependent differences in voluntary physical activity

“…However, early exposure to varying environmental chemicals may suppress PA in one or both sexes. For instance, developmental exposure to BPA suppresses PA in female but not male California mice (Johnson et al 2015); whereas, early exposure to Mn and dichlorovos reduces PA levels in males (Betharia and Maher 2012; Lazarini et al 2004). Further studies in this area may reveal that there are complex interactions between genetic background and environmental factors, i.e.…”

“…2. The model might explain why developmental exposure to BPA suppressed voluntary PA in female but not male California mice (Johnson et al 2015). This plausible mechanism might also account for observed sex differences in general PA levels that can be influenced by stage of the estrous or menstrual cycle in females.…”

“…Females but not males developmentally exposed to BPA show less spontaneous activity, sleep more hours, and show disturbances in carbohydrate vs. fat metabolism (Fig. 1) (Johnson et al 2015). An early study testing behavioral performance in the elevated plus maze and hole board of Sprague-Dawley rats perinatally exposed to BPA suggests that motivation to explore is reduced in both adult males and females, but females also demonstrate reduced motor activity (Farabollini et al 1999).…”

Metabolism disrupting chemicals and metabolic disorders

“…A variety of stressors including high-fat, high-sugar diets, low protein diets and environmental chemicals can induce transgenerational inheritance of metabolic diseases [609]. Several recent papers have shown that the effects of MDC exposure in pregnant F0 animals were propagated until at least the F3 generation (reviewed in [309, 610, 611]).…”

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

“…However, it is also becoming apparent that exposure to BPA, especially during development, can result in neurobehavioral and other disorders [2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14]. Examples of neurobehavioral disorders that have been associated with BPA in rodent and other animal models include cognitive deficits, increased anxiety, socio-sexual deficiencies, compromised maternal and/or paternal care, and decreased voluntary physical activity [15; 16; 17; 18; 19; 20; 21; 22; 23]. Evidence also links exposure to this chemical to neurological disorders, such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) [2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 24; 25; 26; 27].…”