Perinatal bisphenol A exposure promotes hyperactivity, lean body composition, and hormonal responses across the murine life course

Abstract

The development of adult-onset diseases is influenced by perinatal exposure to altered environmental conditions. One such exposure, bisphenol A (BPA), has been associated with obesity and diabetes, and consequently labeled an obesogen. Using an isogenic murine model, we examined the effects of perinatal exposure through maternal diet to 50 ng (n=20), 50 μg (n=21), or 50 mg (n=18) BPA/kg diet, as well as controls (n=20) on offspring energy expenditure, spontaneous activity, and body composition at 3, 6, and 9 mo of age, and hormone levels at 9 and 10 mo of age. Overall, exposed females and males exhibited increased energy expenditure (P<0.001 and 0.001, respectively) throughout the life course. In females, horizontal and vertical activity increased (P=0.07 and 0.06, respectively) throughout the life course. Generally, body composition measures were not different throughout the life course in exposed females or males (all P>0.44), although body fat and weight decreased in exposed females at particular ages (all P<0.08). Milligram-exposed females had improved glucose, insulin, adiponectin, and leptin profiles (all P<0.10). Thus, life-course analysis illustrates that BPA is associated with hyperactive and lean phenotypes. Variability across studies may be attributable to differential exposure duration and timing, dietary fat and phytoestrogen content, or lack of sophisticated phenotyping across the life course.

Figure 1.

Energy expenditure (ml/kg/h) measured by indirect calorimetry over a 72-h period. Oxygen consumption (A) and carbon dioxide production (B) across the life course, stratified by offspring sex. P values represent nanogram (n=10 female, 10 male), microgram (n=10 female, 11 male), or milligram (n=9 female, 9 male) BPA-exposed offspring compared to control offspring (n=10 female, 10 male).

Figure 2.

Spontaneous activity (counts/h) measured via IR photobeam detection average over a 72-h period. Horizontal (A) and vertical (B) activity across the life course, stratified by offspring sex. P values represent nanogram (n=10 female, 10 male), microgram (n=10 female, 11 male), or milligram (n=9 female, 9 male) BPA-exposed offspring compared to control offspring (n=10 female, 10 male).

Figure 3.

Food intake (g) across the life course, measured by powdered food on a precision scale over a 72-h period, stratified by offspring sex. P values represent nanogram (n=10 female, 10 male), microgram (n=10 female, 11 male), or milligram (n=9 female, 9 male) BPA-exposed offspring compared to control offspring (n=10 female, 10 male).

Figure 4.

Body composition (g) measured via nuclear magnetic resonance. Body weight (A) and body fat (B) across the life course, stratified by offspring sex. P values represent nanogram (n=10 female, 10 male), microgram (n=10 female, 11 male), or milligram (n=9 female, 9 male) BPA-exposed offspring compared to control offspring (n=10 female, 10 male).

Figure 5.

Hormones measured at 9 or 10 mo of age. A) Glucose (mg/dl) and insulin (ng/ml), measured via a fasting OGTT at baseline and at 15, 30, 60, and 120 min at 9 mo of age. P values represent nanogram (n=9 female), micrograms (n=10 female), or milligrams (n=9 female) BPA-exposed offspring compared to control offspring (n=9 female); nanogram and control offspring sample sizes were altered due to early decease. B) Glucose (mg/dl) and insulin (ng/ml), measured via a fasting OGTT at baseline and at 15, 30, 60, and 120 min at 9 mo of age. P values represent nanogram (n=10 male), microgram (n=11 male), or milligram (n=9 male) BPA-exposed offspring compared to control offspring (n=10 male). C) HOMA-IR calculated from fasting OGTT scores. D, E) Adiponectin (μg/ml; D) and leptin (ng/ml; E) measured via ELISA at 10 mo of age. P values represent nanogram (n=9 female, 10 male), microgram (n=10 female, 11 male), or milligram (n=9 female, 9 male) BPA-exposed offspring compared to control offspring (n=9 female, 10 male); nanogram and control offspring sample sizes were altered due to early decease. *P < 0.10, **P < 0.05.