在小鼠中,dolutegravir诱导的神经管缺陷是叶酸反应敏感的
Gabriel L Tukeman1, Hui Wei1, Ying L Lin1
1Baylor College of Medicine, Department of Molecular and Cellular Biology.
AIDS (London, England)
|June 29, 2023
概括
孕产妇的叶酸水平显著影响暴露于多卢特格拉维尔 (DTG) 的小鼠的出生缺陷. 怀孕期间足够的叶酸摄入量可以预防神经管缺陷 (NTD) 和与DTG相关的其他发育问题.
科学领域:
- 生殖毒理学 生殖毒理学
- 发育生物学是发展生物学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 博茨瓦纳特塞帕莫研究表明,在怀孕期间暴露于多卢特格拉维尔 (DTG) 的婴儿中,神经管缺陷 (NTD) 增加了9倍.
- 母亲的叶酸状况是影响NTD风险的已知因素.
研究的目的:
- 为了研究叶酸水平对怀孕期间用DTG治疗的小鼠出生结果的影响.
- 为了评估DTG的发育毒性与母亲的叶酸状况相关.
主要方法:
- 怀孕的CD-1小鼠被食正常或低叶酸水平的饮食.
- 小鼠从胚胎日E6.5到E12.5.5接受了治疗剂量或超治疗剂量的DTG.
- 胎儿发育在预产期 (E18.5) 评估了严重,内部和骨异常.
主要成果:
- 脑外症是一种NTD,观察到来自低叶酸饮食的母胎的胎儿暴露于DTG.
- 在DTG暴露的正常和低叶酸饮食组的胎儿中发生了口腔裂.
- 在低叶酸饮食的小鼠中,DTG暴露导致NTD增加.
结论:
- 在怀孕期间摄入足够的食叶酸可以减轻小鼠中DTG诱导的发育缺陷.
- 低母乳叶酸状况可能导致怀孕个体中DTG暴露时观察到的NTD风险升高.
- 叶酸状况应在未来对DTG相关NTD风险的研究中被视为关键因素.
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