后代
脂质体
转录组
内分泌学
生物
内科学
脂质代谢
代谢组
怀孕
医学
基因表达
代谢物
生物化学
遗传学
基因
作者
Hoa L. Nguyen,Lingyun Li,Akifumi Eguchi,Tetsuro Agusa,Kimika Yamamoto,Kurunthachalam Kannan,Eun Young Kim,Hisato Iwata
标识
DOI:10.1016/j.scitotenv.2022.153990
摘要
Our previous studies demonstrated that prenatal bisphenol A (BPA) exposure affected the hepatic transcriptome and lipidome in rat offspring in a sex- and age-dependent manner. In this study, we investigated the effects of gestational exposure to BPA on the rat dams, after weaning period, and compared them with those of their offspring. Our results showed alterations in hepatic transcriptome related to insulin signaling, circadian rhythm, and infectious disease pathways in BPA-treated dams even 4 weeks after the exposure, whereas slight modifications on the lipid profile were found. Alterations in lipid and transcriptome profiles were more prominent in the prenatally BPA-exposed offspring at postnatal day (PND) 1 and 21 than those in the dams, suggesting that in utero exposure to BPA is more serious than exposure in the adulthood. Cryptochrome-1 (Cry1) and peroxisome proliferator-activated receptor delta (Ppard) were commonly altered in both dams and offspring. Nevertheless, the results of DIABLO (Data Integration Analysis for Biomarker discovery using Latent cOmponents), showed that multi-omics data successfully distinguished the exposed dams from the corresponding controls and their offspring with a high level of accuracy. The accuracy rates in BPA50 models (including control and 50 μg BPA/kg bw/day exposed groups) were smaller than those in BPA5000 models (control and 5000 μg BPA/kg bw/day exposed groups), suggesting dose-dependent severity in BPA effects. Palmitic acid and genes related to circadian rhythm, insulin responses, and lipid metabolism (e.g., 1-acylglycerol-3-phosphate O-acyltransferase 2 (Agpat2), B-cell CLL/lymphoma 10 (Bcl10), Cry1, Harvey rat sarcoma virus oncogene (Hras), and NLR family member X1 (Nlrx1)) were identified through DIABLO models as novel biomarkers of effects of BPA across two generations.
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