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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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE107198 | GEO | 2018/08/27

REPOSITORIES: GEO

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Project description:Compairsion of transcriptional profiles of heart and skeletal muscle tissue of fetal rhesus monkey exposed to maternal Bisphenol A or vehicle during early or late gestaion. Maternal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac and skeletal muscle development have not been assessed. Given that maternal BPA crosses placenta and reaches developing fetus, examining the physiological consequences of gestational exposure during development is of research significance. Therefore, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart and skeletal muscle transcriptome. Pregnant monkeys were administered daily oral doses (400 M-BM-5g/kg body weight) of BPA during early (50 M-bM-^@M-^S100 M-BM-1 2 days post conception, dpc) or late (100 M-BM-1 2 dpc - term), gestation. At the end of treatment, fetal heart tissues; left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA) and skeletal muscle; biceps femoris (BFM), were collected. Transcriptome expression was assessed using genome-wide microarray in each of the tissues and compared paired-wise between the BPA and matched control fetuses. Our results show that maternal BPA exposure alters transcriptional profile of several coding and non-coding genes in fetal heart and skeletal muscle. Pregnant rhesus monkey were administered a daily oral dose of 400 M-NM-<g/kg. body weight of Bisphenol A (BPA) or vehicle (CON) either during early (50M-bM-^@M-^S100 M-BM-1 2 days) or late (100 M-BM-1 2 daysM-bM-^@M-^Sterm) gestation. Gene expression profiles of each of the heart chambers (left ventricle, LV; right ventricle, RV; left atrium, LA; and right atrium, RA) and skeletal muscle (biceps femoris, BFM) were analyzed using microarrays and compared between the BPA exposed and matched control fetuses. A total of 12 samples were analyzed for each tissue; LV, RV, LA, RA and BFM. This includes 6 samples at each time period (early vs. late gestation) and 3 biological replicates for each treatment (BPA, n=3; control, n=3).

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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

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