Exposure to PCB126 during the nursing period reversibly impacts early-life glucose tolerance

Abstract

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal days (PND) 3, 10, and 17 (n = 9 per group). Offspring body weight, lean and fat mass, and glucose tolerance were recorded every three weeks. PCB126 treatment did not alter dam nor offspring body weight (p > 0.05). PCB126-exposed male and female offspring displayed normal body composition (p > 0.05) relative to vehicle-exposed offspring. However, both male and female offspring that were exposed to PCB126 during the nursing period had significantly impaired glucose tolerance at 3 and 9 weeks of age (p < 0.05). At 6 and 12 weeks of age, no impairments in glucose tolerance existed in offspring (p > 0.05). Our current study demonstrates that exposure to PCB126 through the mother's milk does not affect short- or long-term body composition but impairs glucose tolerance in the short-term.

Keywords: DOHaD (development origins of health and disease); developmental programming of adult disease; diabetes; lactation; mice; obesity; polychlorinated biophenyls.

Figure 1

PCB126 exposure during the nursing period does not affect dam or offspring body weight. (A) The body weight of vehicle and PCB126-treated dams from parturition to weaning are shown. Dams received treatments respective to their experimental grouping 3, 10, and 17 days after delivery. Dam body weight values are representative of the mean ± SEM (n = 9 mice per group). The body weight of (B) 3-week-old (C) 6-week-old, (D) 9-week-old, and (E) 12-week-old offspring born to dams exposed to PCB126 or vehicle during the nursing period are shown. Offspring body weight values are provided as means of litter means ± SEM (n = 9 per group). Two-factor repeated measures ANOVA and two-factor ANOVA were respectively used to analyze dam and offspring body weight.

Figure 2

Maternal PCB126 exposure during the nursing period does not alter body composition. Body composition (lean and fat mass) of offspring was measured at 3, 6, 9, and 12 weeks of age via EchoMRI. Shown are the offspring data from 3 (A, B), 6 (C, D), 9 (E, F) and 12 (G, H) weeks of age. Fat mass and lean mass values are presented as the mean of litter means ± SEM (n = 9 per group). Data shown were analyzed using two-factor ANOVA.

Figure 3

Offspring born to PCB126-exposed dams exhibit short-term impairments in glucose tolerance. Measurements of glucose levels in offspring are shown in response to intraperitoneal glucose injection. The glucose tolerance testing of (A) 3-week-old, (C) 6-week-old, (E) 9-week-old, and (G) 12-week-old vehicle- and PCB-exposed offspring. Significant sex-specific differences and treatment differences in glucose tolerance were respectively observed in male offspring and PCB126-exposed offspring (A, E, and G; p < 0.05 for all). Total AUC of (B) 3-week-old and (D) 6-week-old, (F) 9-week-old, and (H) 12-week-old vehicle- and PCB-exposed offspring blood glucose levels are shown. Significant differences in treatment were observed in offspring at 3 weeks of age (B, p < 0.001) and 9 weeks of age (D, p = 0.049), while significant differences in sex was observed at 12 weeks of age (H, p < 0.001). Values are shown as the mean ± SEM (n = 9 per group). Two-factor ANOVA was used to analyze glucose tolerance and AUC data. Specifically, two-factor ANOVA was used at each time-point for glucose tolerance data analyses. The # sign designates a main effect of sex while the * designates a main effect of PCB treatment (P < 0.05). Significant interactions between treatment and sex are indicated by §.