Bisphenol A exposure prenatally delays bone development and bone mass accumulation in female rat offspring via the ERβ/HDAC5/TGFβ signaling pathway.

Previous studies have suggested that bisphenol A (BPA) has a toxic effect on bone development; however, its pathological mechanism has not been fully elucidated. In the present study, pregnant Wistar rats were intragastrically administered BPA (10 μg/kg per day) during gestational days 14-21. Then, bone tissues were obtained from neonatal rats on postnatal day 1 for histological analysis, and the bone mass of adult rat offspring was analyzed by micro-CT at postnatal week 10. Furthermore, osteoprogenitors from neonatal rats were obtained and treated with various concentrations of BPA in vitro to clarify the associated mechanism. In vivo, we found that prenatal BPA exposure reduced body weight and body length in female neonatal rats but not in male neonatal rats. Meanwhile, BPA exposure during pregnancy delayed bone development and reduced bone mass only in female rat offspring. Moreover, BPA exposure during pregnancy inhibited osteogenic function and downregulated the transforming growth factor β (TGF β) signaling pathway in the bone tissue of female neonatal rats. Our in vitro findings further indicated that various concentrations of BPA suppressed the osteogenic function of osteoprogenitors by downregulating the TGFβ signaling pathway. Meanwhile, BPA downregulated H3K9ac and expression levels of TGFβ via the ERβ/HDAC5 signaling pathway. Collectively, this research revealed that prenatal BPA exposure impairs bone development and bone mass accumulation in female rat offspring, which was attributed to inhibitory osteogenic function via the ERβ/HDAC5/TGFβ signaling pathway.