Reduction in valproic acid-induced neural tube defects by maternal immune stimulation: role of apoptosis.
Reduction in valproic acid-induced neural tube defects by maternal immune stimulation: role of apoptosis.
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DOI：
10.1002/bdrb.21018
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发表时间：
2012-08
期刊：
影响因子：
--
通讯作者：
Hrubec T
中科院分区：
文献类型：
--
作者：
Mallela M;Hrubec T
发育过程中致畸性的细胞凋亡失调可能是导致出生缺陷的机制。在妊娠早期服用丙戊酸（VA）会导致神经管缺陷（NTDs）。在啮齿类动物中，对母体免疫系统的非特异性刺激已被证明可以减少各种致畸源诱导的胎儿畸形，包括NTDs。本研究探讨了母体免疫刺激减少细胞凋亡在预防va诱导的CD-1小鼠NTDs中的作用。利用IFNγ非特异性母体免疫刺激预防va诱导的NTDs，以评估IFNγ减少细胞凋亡在这种保护机制中的作用。流式细胞术定量细胞凋亡。末端转移酶dUTP尼克末端标记法定位细胞凋亡。在VA暴露的正常和异常胚胎中，沿神经管观察到细胞凋亡增加，提示与VA致畸性有关。暴露于VA的正常胚胎中细胞凋亡增加表明，除了细胞凋亡外，VA还可能改变其他细胞过程，如细胞增殖和分化。在IFNγ + VA坝封闭神经管的胚胎中，凋亡水平与对照组相似，表明对VA诱导的细胞凋亡有抗性，并对VA的致畸性有保护作用。在IFNγ + VA暴露的神经管开放胚胎中，母体免疫刺激未能调节细胞凋亡，导致NTD。总的来说，这些结果表明，VA改变了发育中的胚胎的几个生物学过程，包括细胞凋亡，从而诱导胎儿畸形。母体免疫刺激对va诱导的胚胎细胞凋亡的抵抗可能与保护机制有关。
Teratogenic deregulation of apoptosis during development is a possible mechanism for birth defects. Administration of valproic acid (VA) during first trimester of pregnancy causes neural tube defects (NTDs). Nonspecific stimulation of the mother’s immune system has been shown to reduce various teratogen-induced fetal malformations including NTDs in rodents. This present study investigated the role of reduced apoptosis by maternal immune stimulation in prevention of VA-induced NTDs in CD-1 mice. Prevention of VA-induced NTDs by nonspecific maternal immune stimulation using IFNγ was employed to evaluate the role of reduced apoptosis by IFNγ in this protective mechanism. Apoptosis was quantified using flow cytometry. Terminal Transferase dUTP Nick End Labeling assay was used to localize the apoptosis. Increased apoptosis, suggesting involvement in VA teratogenicity, was observed along the neural tube in both normal and abnormal embryos from VA-exposed dams. Increased apoptosis in normal VA-exposed embryos suggests that VA may alter other cellular processes such as cell proliferation and differentiation in addition to apoptosis. Apoptotic levels in embryos with closed neural tubes from IFNγ + VA dams were similar to controls indicating resistance to VA-induced apoptosis and protection against teratogenicity of VA. In IFNγ + VA exposed embryos with open neural tubes, maternal immune stimulation failed to regulate apoptosis resulting in an NTD. Overall, these results suggest that VA alters several biological processes including apoptosis in the developing embryos to induce fetal malformations. Resistance to VA-induced apoptosis in embryos resulting from maternal immune stimulation may be involved in protective mechanism.
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影响因子：
1
作者：
Kisseberth, William C.;Murahari, Sridhar;Chen, Ching-Shih
通讯作者：
Chen, Ching-Shih
DOI：
10.1002/bdrb.20062
发表时间：
2006-02-01
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.3
作者：
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影响因子：
3.8
作者：
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影响因子：
3.6
作者：
Defoort, EN;Kim, PM;Winn, LM
通讯作者：
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