Effects of prenatal bisphenol A exposure on the hepatic transcriptome and proteome in rat offspring

Developmental exposure to bisphenol A (BPA) is associated with liver dysfunction and diseases in adulthood. The aims of this study were to assess the effects of prenatal BPA exposure on the hepatic transcriptome and proteome in female and male offspring and to understand adverse outcome pathways (AO...

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Published in:The Science of the total environment 2020-06, Vol.720, p.137568-137568, Article 137568
Main Authors: Nguyen, Hoa Thanh, Yamamoto, Kimika, Iida, Midori, Agusa, Tetsuro, Ochiai, Mari, Guo, Jiahua, Karthikraj, Rajendiran, Kannan, Kurunthachalam, Kim, Eun-Young, Iwata, Hisato
Format: Article
Language:English
Subjects:
Adverse outcome pathway
Animals
Benzhydryl Compounds
Bisphenol A
Female
Liver
Male
Phenols
Pregnancy
Prenatal exposure
Prenatal Exposure Delayed Effects
Proteome
Proteomics
Rats
Rats, Wistar
Transcriptome
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Summary:Developmental exposure to bisphenol A (BPA) is associated with liver dysfunction and diseases in adulthood. The aims of this study were to assess the effects of prenatal BPA exposure on the hepatic transcriptome and proteome in female and male offspring and to understand adverse outcome pathways (AOPs) to observed phenotypic effects. Pregnant Wistar rats were exposed to 50 or 5000 μg BPA/kg bw/day, or 17β-estradiol (E2, 50 μg/kg bw/day) from embryonic day 3 to 18. The liver transcriptome and proteome profiles were analyzed in the newborn (postnatal day 1; PND1) and weaning (PND21) rat offspring. Based on the differentially expressed genes/proteins derived from transcriptome and proteome profiles, we performed pathway, transcription factor, and disease enrichment analyses. A principal component analysis of transcriptome data demonstrated that prenatal BPA exposure caused masculinization of the hepatic transcriptome in females. Both of transcriptomic and proteomic data showed that prenatal BPA exposure led to the disruption of cell cycle, lipid homeostasis, and hormone balance in offspring. Most of the effects at the transcript level were extended from newborn to weaning in males, but were moderated until weaning in females. The alterations at the transcript and protein levels were accordant with the observation of increases in body weight and anogenital distance and changes in hepatosomatic index in the offspring. Collectively, we constructed AOPs with evidence of sex- and age-specific actions of prenatal BPA exposure in the offspring. [Display omitted] •We investigated hepatic transcriptome and proteome of rat offspring prenatally exposed to bisphenol A (BPA).•BPA exposure disrupted the cell cycle, lipid homeostasis, and steroid hormone metabolism.•Sex- and age-specific adverse outcome pathways of prenatal BPA exposure were developed.
ISSN:0048-9697
1879-1026
DOI:10.1016/j.scitotenv.2020.137568