Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome.
Sex-Specific Effects of Early-Life Iron Deficiency and Prenatal Choline Treatment on Adult Rat Hippocampal Transcriptome.
复制标题
DOI：
10.3390/nu15061316
复制
发表时间：
2023-03-07
期刊：
影响因子：
5.9
通讯作者：
Tran PV
中科院分区：
文献类型：
--
作者：
Liu SX;Fredrickson TK;Calixto Mancipe N;Georgieff MK;Tran PV
背景：胎儿-新生儿缺铁（ID）会导致长期的神经认知和情感功能障碍。临床和临床前研究表明，生命早期的智力缺陷会产生性别特异性的影响。然而，人们对生命早期 ID 诱导的性别特异性对神经基因调控的影响的分子机制知之甚少。目的：阐明胎儿-新生儿 ID 和产前胆碱治疗诱导的成年大鼠海马性别特异性转录组变化。方法：从妊娠第 2 天（G）到产后第 7 天（P），给怀孕大鼠喂食缺铁（4 mg/kg Fe）或铁充足（200 mg/kg Fe）饮食，并从 G11-18 补充或不补充胆碱（5 g/kg 胆碱）。从 P65 两性后代中收集海马并分析基因表达的变化。结果：生命早期 ID 和胆碱治疗均诱导成年雌性和雄性大鼠海马体的转录变化。两性都表现出 ID 诱导的基因网络改变，导致神经炎症增强。在雌性中，ID诱导的变化表明氧化磷酸化和脂肪酸代谢活性增强，这与雄性中的ID效应相反。产前补充胆碱引起了最强烈的基因表达变化，特别是在缺铁动物中，它部分缓解了 ID 引起的失调。补充胆碱还改变了铁充足大鼠的海马转录组，显示出有益和不利的影响。结论：这项研究以性别特异性方式对铁和胆碱调节的基因表达进行了公正的整体评估，对雌性大鼠的影响大于雄性大鼠。我们的新发现强调了受铁和胆碱调节的潜在性别特异性基因网络，有待进一步研究。
Background: Fetal-neonatal iron deficiency (ID) causes long-term neurocognitive and affective dysfunctions. Clinical and preclinical studies have shown that early-life ID produces sex-specific effects. However, little is known about the molecular mechanisms underlying these early-life ID-induced sex-specific effects on neural gene regulation. Objective: To illustrate sex-specific transcriptome alterations in adult rat hippocampus induced by fetal-neonatal ID and prenatal choline treatment. Methods: Pregnant rats were fed an iron-deficient (4 mg/kg Fe) or iron-sufficient (200 mg/kg Fe) diet from gestational day (G) 2 to postnatal day (P) 7 with or without choline supplementation (5 g/kg choline) from G11–18. Hippocampi were collected from P65 offspring of both sexes and analyzed for changes in gene expression. Results: Both early-life ID and choline treatment induced transcriptional changes in adult female and male rat hippocampi. Both sexes showed ID-induced alterations in gene networks leading to enhanced neuroinflammation. In females, ID-induced changes indicated enhanced activity of oxidative phosphorylation and fatty acid metabolism, which were contrary to the ID effects in males. Prenatal choline supplementation induced the most robust changes in gene expression, particularly in iron-deficient animals where it partially rescued ID-induced dysregulation. Choline supplementation also altered hippocampal transcriptome in iron-sufficient rats with indications for both beneficial and adverse effects. Conclusions: This study provided unbiased global assessments of gene expression regulated by iron and choline in a sex-specific manner, with greater effects in female than male rats. Our new findings highlight potential sex-specific gene networks regulated by iron and choline for further investigation.
登录
查看更多内容
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
3
作者：
Albert PR;Vahid-Ansari F;Luckhart C
通讯作者：
Luckhart C
产前铁缺乏症和补充胆碱与大鼠海马中的jARID1b和BDNF相互作用。
影响因子：
5.9
作者：
Liu SX;Barks AK;Lunos S;Gewirtz JC;Georgieff MK;Tran PV
通讯作者：
Tran PV
影响因子：
4.2
作者：
Barks, Amanda;Fretham, Stephanie J. B.;Tran, Phu, V
通讯作者：
Tran, Phu, V
影响因子：
3.5
作者：
Duarte-Guterman, Paula;Yagi, Shunya;Galea, Liisa A. M.
通讯作者：
Galea, Liisa A. M.