Perinatal exposure to bisphenol a alters early adipogenesis in the rat

Abstract

Background: The causes of the current obesity pandemic have not been fully elucidated. Implication of environmental endocrine disruptors such as bisphenol A (BPA) on adipose tissue development has been poorly investigated.

Objectives: The aim of the present study was to evaluate the effects of perinatal exposure to BPA on early adipose storage at weaning.

Methods: Pregnant Sprague-Dawley rats had access to drinking water containing 1 mg/L BPA from day 6 of gestation through the end of lactation. Pups were weaned on postnatal day (PND) 21. At that time, we investigated perigonadal adipose tissue of pups (weight, histology, gene expression). For the remaining animals, we recorded body weight and food intake for animals on either standard chow or a high-fat diet.

Results: Gestational exposure to BPA did not alter the sex ratio or litter size at birth. On PND1, the weight of male and female BPA-exposed pups was increased. On PND21, body weight was increased only in females, in which parametrial white adipose tissue (pWAT) weight was increased about 3-fold. This excess of pWAT was associated with adipocyte hypertrophy and overexpression of lipogenic genes such as C/EBP-alpha (CAAT enhancer binding protein alpha), PPAR-gamma (peroxisome proliferator-activated receptor gamma), SREBP-1C (sterol regulatory element binding protein-1C), LPL (lipoprotein lipase), FAS (fatty acid synthase), and SCD-1 (stearoyl-CoA desaturase 1). In addition, gene expression of SREBP-1C, FAS, and ACC (acetyl-CoA carboxylase) was also increased in liver from BPA-exposed females at PND21, without a change in circulating lipids and glucose. After weaning, perinatal BPA exposure predisposed to overweight in a sex- and diet-dependent manner. We observed no change in food intake due to perinatal BPA exposure in rats on either standard chow or a high-fat diet.

Conclusions: Perinatal exposure to a low dose of BPA increased adipogenesis in females at weaning. Adult body weight may be programmed during early life, leading to changes dependent on the sex and the nutritional status. Although further studies are required to understand the mechanisms of BPA action in early life, these results are particularly important with regard to the increasing prevalence of childhood obesity and the context-dependent action of endocrine disruptors.

Keywords: adipocyte; adipose tissue; bisphenol A; food intake; obesity.

Figure 1

Effect of perinatal exposure to 1 mg/L BPA on body weight of rat pups at PND1 (A, males; B, females) and PND21 (C, males; D, females). Results are mean ± SEM. In (A), n = 45 BPA-exposed males from eight litters; n = 55 control males from eight litters. In (B), n = 50 BPA-exposed females from eight litters; n = 47 control females from eight litters. In (C), n = 32 BPA-exposed males from six litters; n = 40 control males from six litters; p = 0.59. In (D), n = 32 BPA-exposed females from six litters; n = 26 control females from six litters. *p < 0.05, and **p < 0.001, compared with controls.

Figure 2

Effect of perinatal exposure to BPA on adipogenesis at weaning (PND21). (A) Weight of eWAT and BAT in male rats. (B) Weight of pWAT and interscapular BAT in female rats; data represent 10 animals from three independent litters. (C) Correlation between pWAT and BAT weight in female rats (n = 10 animals per group; r² = 0.74; p < 0.001). (D) Representative histologic sections of pWAT from control (top) and BPA-exposed females (bottom). (E, F) Relative mRNA levels [in arbitrary units (AU)] in pWAT of female rats at weaning (n = 9–10 animals in each group from three litters). Results shown in A, B, E, and F are mean ± SEM. *p < 0.05, **p < 0.001, and ^#p < 0.002, compared with controls.

Figure 3

Effect of perinatal exposure to BPA on gene expression in liver and circulating metabolites in females at weaning (PND21). (A) Relative mRNA levels [in arbitrary units (AU)] in liver (n = 10 animals per group from three litters). Results are means ± SEM. (B–E) Circulating levels of TG (B), NEFA (C), total cholesterol (D), and glucose (E) in plasma (n = 10 animals per group from three litters). *p < 0.05, ^##p < 0.01, and ^†p < 0.02, compared with controls.

Figure 4

Effect of a high-fat diet on body weight of male (A, B) and female (C, D) rats perinatally exposed to BPA. . Animals were fed standard chow (A, C) or the high-fat diet (B, D) during weeks 4–14; n = 8–12 animals per group. Note the smallest curve of body weight in A and C (chow diet) compared with B and D (high-fat diet). *p < 0.05 compared with control,