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在植入过程中母亲对臭氧的暴露促进了男性青少年肝脏中的女性化转录基因特征

Janice A Dye¹, Erica J Stewart², Mette C Schladweiler¹

¹Cardiopulmonary Immunotoxicology Branch, Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, Research Triangle Park, Durham, NC 27711, USA.

|January 27, 2025

概括

孕妇在怀孕期间暴露于臭氧会导致小鼠幼的胎儿生长受限. 在子宫内暴露于臭氧的男性后代表现出类似女性的肝脏基因表达模式,这表明潜在的肝脏女性化.

科学领域:

环境毒理学环境毒理学
发展生物学发展生物学
基因组学就是基因组学.

背景情况:

母亲暴露于臭氧等环境毒素可能会影响胎儿的发育.
在关键妊娠期内暴露于臭氧会导致胎儿生长受限.
暴露于胎儿生长限制的后代在以后的生活中表现出改变的代谢风险.

研究的目的:

研究臭氧诱导的胎儿生长限制对雄性和雌性老鼠后代青少年肝转录组的影响.
在子宫内暴露于臭氧后,对肝脏的性别特异性转录基因变化进行表征.
探索胎儿生长受限后代肝脏代谢变化的潜在机制.

主要方法:

怀孕的Long-Evans大鼠在妊娠5日和6日期间暴露在过空气或0.8ppm臭氧中.
从男性和女性后代收集了肝脏组织,大约在出生后48天,用于RNA测序.
进行了差异基因表达分析和途径分析,以确定转录基因变异.

主要成果:

在植入过程中暴露在臭氧中,与雌性相比,男性后代的肝脏基因表达显著改变.
来自暴露于臭氧的水的男性后代表现出与女性后代相似的转录组图案.
受影响的男性的上调途径包括Sirtuin信号传递,Orexin信号传递,雌激素受体信号传递和能量代谢.

结论:

母亲在植入期间暴露于臭氧会导致男性后代肝转录组的"女性化".
由母亲暴露于臭氧引起的胎儿生长限制可能会增加男性后代肝脏女性化的风险.
需要进一步的研究来阐明发育性营养不良和男性肝脏女性化之间的联系.

关键词:

空气污染空气污染发展性重编程发展性重编程肝脏女性化肝脏女性化臭氧层中的臭氧.性别差异的性别差异.

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