Abulehia Hala, Mohd Nor Noor Shafina, Sheikh Abdul Kadir Siti Hamimah
Institute of Medical Molecular Biotechnology (IMMB), Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Jalan Hospital, Sungai Buloh, Malaysia.
Department of Paediatrics, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Kampus Sungai Buloh, Jalan Hospital, Sungai Buloh, Malaysia.
Birth Defects Res. 2025 Feb;117(2):e2450. doi: 10.1002/bdr2.2450.
Bisphenol A (BPA) is a ubiquitous industrial compound found in an enormous variety of consumer goods such as plastics, epoxy resins, and thermal paper. Despite its widespread usage, the effects of BPA on the risk and development of metabolic syndrome are not fully understood. Prenatal exposure to BPA has been shown to disrupt the development of offspring's metabolically active tissues and increase their susceptibility to the adverse consequences of a trans-fat diet (TFD).
In this experiment, pregnant rats (n = 18) were randomly separated into three groups. These groups were treated from pregnancy day (PD) 2 to PD 21. Subsequently, the male offspring of these rats were provided either a normal-diet (ND) or a TFD from 3rd postnatal week (PNW) to 14th PNW. Then, protein expression of PPAR-γ and global DNA methylation were assessed in the adult rat offspring that were exposed to in utero BPA and subjected to postnatal TFD intake.
The study findings have shown that there was no association between prenatal exposure to BPA and/or TFD consumption and PPAR-γ protein expression within all the study groups in the liver tissue. On the other hand, changes at the molecular level, as reflected by the global DNA hypermethylation induced by prenatal BPA and postnatal TFD intake in adult male SD rat offspring (PNW 14).
This study underscores the potential impact of prenatal BPA exposure and postnatal TFD intake on epigenetic regulation, as evidenced by global DNA hypermethylation, despite no observable changes in PPAR-γ protein expression. These findings suggest that early-life environmental exposures may predispose individuals to metabolic disruptions, including diabetes and obesity, in adulthood or future generations.
双酚A(BPA)是一种普遍存在的工业化合物,存在于各种各样的消费品中,如塑料、环氧树脂和热敏纸。尽管其使用广泛,但BPA对代谢综合征风险和发展的影响尚未完全了解。已表明产前暴露于BPA会扰乱后代代谢活跃组织的发育,并增加其对反式脂肪饮食(TFD)不良后果的易感性。
在本实验中,将18只怀孕大鼠随机分为三组。这些组从妊娠第2天(PD)至第21天接受处理。随后,这些大鼠的雄性后代从出生后第3周(PNW)至第14周接受正常饮食(ND)或TFD。然后,在暴露于子宫内BPA并在出生后摄入TFD的成年大鼠后代中评估PPAR-γ的蛋白表达和整体DNA甲基化。
研究结果表明,在肝脏组织的所有研究组中,产前暴露于BPA和/或TFD消费与PPAR-γ蛋白表达之间没有关联。另一方面,成年雄性SD大鼠后代(PNW 14)中,产前BPA和出生后TFD摄入诱导的整体DNA高甲基化反映了分子水平的变化。
本研究强调了产前BPA暴露和出生后TFD摄入对表观遗传调控的潜在影响,整体DNA高甲基化证明了这一点,尽管PPAR-γ蛋白表达没有明显变化。这些发现表明,早期环境暴露可能使个体在成年期或后代易患包括糖尿病和肥胖在内的代谢紊乱。