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怀孕和哺乳期对小鼠的双甲暴露:对寡细胞和髓化产生性别特异性影响

Vanessa Naffaa¹, Juliette Van Steenwinckel², Romain Magny¹

¹Université Paris Cité, CNRS, CiTCoM, Paris 75006, France.

|January 1, 2025

概括

在发育过程中接触双甲 (BPA) 会改变雌性小鼠的髓脂组成,这表明性别特异性,对大脑发育的转录后影响. 这些变化是暂时的,并没有影响与脂质代谢相关的基因表达.

科学领域:

神经科学是一个神经科学.
内分泌学在内分泌学.
发展生物学发展生物学

背景情况:

双A (BPA) 是一种内分泌干扰物,与不良的大脑发育结果有关.
寡细胞和髓化对于正确的大脑功能和发育至关重要.
在BPA神经发育作用的基础上,细胞和分子机制在很大程度上是未知的.

研究的目的:

研究孕期和哺乳期BPA暴露对小鼠大脑发育的影响.
阐明BPA对髓化影响的取决于性别的细胞和分子机制.

主要方法:

在怀孕和哺乳期间,小鼠暴露于BPA (25和250μg/L).
骨髓脂组成在产后日P15,P30和P60进行了分析.
转录基因和染色质可访问性分析在寡头质细胞上进行.

主要成果:

暴露于BPA以性别依赖的方式改变了髓脂质重塑,主要影响女性.
雌性髓脂组成的变化 (酸丁胆的减少,糖脂的增加) 类似于更成熟的髓,并且是短暂的 (仅P15).
转录组分析显示,女性脂质代谢基因没有变化,这表明后转录调节;男性基因表达与突触传输相关的变化.

结论:

在关键的发育窗口期间,BPA暴露会导致髓脂组成的性别特异性,短暂的变化.
转录后的机制,可能涉及伴侣介导的蛋白质折叠和RNA拼接,介导BPA对雌性髓的影响.
染色体可访问性变化取决于性别,并且与转录没有一致的相关性,除了Cwc22位点.

关键词:

双 A 是一种双.脂质组 (lipidome) 是一种脂质组 (lipidome) 的组成部分.骨髓蛋白是什么意思骨髓蛋白是什么意思骨髓化骨髓化氧基基细胞 (Oligodendrocytes) 是一种类型的细胞.转录组转录组就是一个转录组.

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