DNA methylomes and RNA transcriptomes in 19-weeks-old CD-1 male epididymal white adipose tissues with or without prenatal exposure to 500 ug/kg/day Bisphenol A

Exposure of mammalian fetuses to endocrine disruptors can increase the risk of adult-onset diseases. For example, we previously showed that exposure of mouse fetuses to bisphenol A (BPA) caused adult-onset obesity. To obtain insights into roles of epigenetic changes in the delayed toxic effects of endocrine disruption, we determined effects of fetal mouse exposure to BPA on genome-wide DNA methylation and mRNA expression in gonadal white adipose tissues by deep sequencing (MBD-seq and RNA-seq), bisulfite pyrosequencing, and real-time qPCR. Pregnant CD-1 mice (F0) were dosed daily with 0, 5, or 500 ug/kg/day BPA during 9-18 dpc, and the weaned F1 animals were fed ad libitum with standard chow until they were sacrificed at 19 weeks old. In the vehicle-exposed F1 animals, fggy promoter showed a clear bimodal pattern of very strong (55-95%) or very weak (5-30%) DNA methylation occurring at nearly equal incidence with no intermediate strength, and promoter hypermethylation completely suppressed mRNA expression. BPA exposure eliminated this naturally occurring dichotomy, shifting fggy promoter towards the hypomethylation state to release transcriptional suppression. Strength of Fggy mRNA expression significantly correlated with increased whole-body weight and gonadal fat weight of males but not females. Bioinformatics studies showed that expression of Fggy mRNA is stronger in mouse white adipose tissues than brown adipose tissues and enhanced in gonadal fat by diet-induced obesity. These observations suggest that prenatal exposure to BPA may disrupt the physiological bimodal nature of epigenetic regulation of fggy in mouse white adipose tissues, possibly contributing to the adult-onset obesity phenotype. Pregnant CD-1 females were exposed to 500 ug/kg/day Bisphenol A or vehicle (oil), and their male fetuses were grown until 19 weeks after birth, when epididymal fat was collected for deep sequencing determination of DNA methylomes (MBD-seq) and RNA transcriptomes (RNA-seq).