Reduced body weight at weaning followed by increased post-weaning growth rate interacts with part-per-trillion fetal serum concentrations of bisphenol A (BPA) to impair glucose tolerance in male mice

Abstract

There is evidence from longitudinal studies that being light at birth and weaning is associated with subsequent rapid weight gain in infants. This is referred to as "centile crossing", which can lead to increased risk of lifetime obesity, glucose dysregulation and type 2 diabetes. Here, pregnant CD-1 mice were hemi-ovariectomized so that the entire litter was contained in one uterine horn to increase variability in fetal growth rate. Pregnant females were implanted on gestation day (GD) 9 with a Silastic capsule containing 6, 60 or 600 μg bisphenol A (BPA). On GD 18 the mean fetal serum unconjugated BPA concentrations were 17, 177 and 1858 pg/ml, respectively. Capsules were not removed, to avoid maternal stress, and were predicted to release BPA for at least 3 weeks. Body weight at weaning was strongly negatively correlated with post-weaning weight gain in both control and BPAtreated male mice, consistent with human data; female offspring were excluded, avoiding complications associated with postpubertal estrogens. Within each treatment group, male offspring were sorted into tertiles based on relative weight gain during the two weeks after weaning, designated as having Rapid (R), Medium (M) or Slow (S) growth rate. BPA exposure was associated with altered growth rate between weaning and postnatal week 12 (young adulthood), when a low-dose (20 mg/kg, i.p.) glucose tolerance test (GTT) was performed. We found altered glucose regulation in response to all doses of BPA. However, glucose tolerance was only significantly impaired (blood glucose levels were elevated) compared to controls in males in the rapid post-weaning growth group exposed perinatally to BPA. We conclude that male mice that are light at weaning, but then experience rapid catch-up growth immediately after weaning, represent a sensitive sub-population that is vulnerable to the metabolic disrupting effects of very low pg/ml fetal serum concentrations of BPA.

Bisphenol A and Type 2 Diabetes Mellitus: A Review of Epidemiologic, Functional, and Early Life Factors

“…Furthermore, perinatal BPA exposure impacts on body weight at weaning as well as the rate of post-weaning growth. The findings from this study suggest that foetal exposure to low-dose BPA is more likely to affect a sensitive subpopulation characterised by early life growth restriction and rapid catchup growth post weaning, which could be at higher risk for the development of T2DM [ 94 ].…”

Composites of NiS2 Microblocks, MoS2 Nanosheets, and Reduced Graphene Oxide for Energy Storage and Electrochemical Detection of Bisphenol A

“…As a result, products containing BPA have penetrated people’s daily lives through reusable plastic bottles, tableware, food, beverage cans, etc. Some evidence points out that BPA can interfere with the normal secretion of hormones even at a dose of a few parts per trillion . Nevertheless, high-performance supercapacitors and ultrasensitive electrochemical sensors are inseparable from their electrode materials.…”

“…Some evidence points out that BPA can interfere with the normal secretion of hormones even at a dose of a few parts per trillion. 2 Nevertheless, highperformance supercapacitors and ultrasensitive electrochemical sensors are inseparable from their electrode materials. Thus, there is a critical need to develop novel electrode materials with high reactivity and catalytic activity used in both energy storage and electrochemical sensors.…”

Leaky Gut as a Potential Culprit for the Paradoxical Dysglycemic Response to Gastric Bypass-Associated Ileal Microbiota

“…This might be due to the different rat strains used between studies (diet-induced obese Wistar rats in the present study vs. Zucker Fatty fa/fa rats in our previous study [ 2 ]). However, when expressed as percentage change in blood glucose levels relative to baseline [ 16 ], two-way ANOVA revealed that glycemic control was worse for germ-free mice that received ileal content from RYGB-treated compared with sham-operated rats ( p = 0.023, main effect of treatment; Figure 1 b) in association with a trend toward increased plasma LPS levels (2.56 ± 0.65 EU/mL vs. 1.18 ± 0.19 EU/mL, respectively, p = 0.11; Figure 1 c). Importantly, body weight was similar between recipient groups (40.4 ± 1.1 g for sham-operated recipients vs. 40.9.56 ± 2.5 g for RYGB-treated recipients, p = 0.8; Figure 1 d) while epididymal white adipose tissue (eWAT) weight tended to be lower for germ-free mice that received ileal content from RYGB-treated compared with sham-operated rats (3.3 ± 0.38 g vs. 4.4 ± 0.71 g, respectively, p = 0.21; Figure 1 e).…”