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PLoS One. 2013 May 10;8(5):e64143. doi: 10.1371/journal.pone.0064143. Print 2013.

Perinatal bisphenol A exposure and adult glucose homeostasis: identifying critical windows of exposure.

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Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.


Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day) at different time of perinatal stage: 1) on days 1-6 of pregnancy (P1-P6, preimplantation exposure); 2) from day 6 of pregnancy until postnatal day (PND) 0 (P6-PND0, fetal exposure); 3) from lactation until weaning (PND0-PND21, neonatal exposure); and 4) from day 6 of gestation until weaning (P6-PND21, fetal and neonatal exposure). At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure.

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