Gender‐dependent differences in the incidence of ochratoxin A‐induced neural tube defects in the Pdn/Pdn mouse
Gender‐dependent differences in the incidence of ochratoxin A‐induced neural tube defects in the Pdn/Pdn mouse
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Pdn/Pdn 小鼠赭曲霉毒素 A 诱导的神经管缺陷发生率存在性别差异
DOI：
10.1111/j.1741-4520.2009.00255.x
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发表时间：
2010
影响因子：
1.3
通讯作者：
I. Naruse
中科院分区：
文献类型：
--
作者：
E. Ueta;Mami Kodama;Y. Sumino;Maho Kurome;Ken;Ryu;I. Naruse
遗传性多指/无脑小鼠胚胎，Pdn/Pdn，表现出抑制Gli 3基因表达。赭曲霉毒素A（OTA）是一种致畸剂，可导致小鼠神经管缺陷（NTD）。我们研究了Pdn/Pdn小鼠中OTA诱导的NTD发生率的性别依赖性差异。在妊娠第7.5天，对与Pdn/+雄性交配的Pdn/+雌性小鼠给予2 mg/kg OTA后，我们在第18天检查了胎儿的基因型、性别和NTD。未治疗的Pdn/Pdn的NTD风险为15.8%，所有NTD胎儿均为雌性。当Pdn/Pdn胚胎暴露于OTA时，NTD的发生率增加到31个Pdn/Pdn胎儿中的16个（51.6%），并且14个雄性Pdn/Pdn胎儿中的10个（71.4%）表现出NTD。根据这些结果，推测OTA处理的雄性Pdn/Pdn中的NTD是由于OTA处理导致的Gli 3抑制和性别相关基因表达改变之间的协同效应。用OTA处理后，在第9天回收胚胎，并研究与Gli 3、端脑形态发生、性腺原基形成和性别依赖性分化相关的基因表达。根据真实的实时聚合酶链反应分析结果，提示OTA处理的雄性Pdn/Pdn中NTD的表现可能是由于Gli 3、Wnt 7 b、Wnt 8b、Fez 1、Barx 1、Lim 1、Dmrt 1、Igf 1、Fog 2、Dax 1和Sox 9之间复杂的基因表达改变，特别是，Barx 1的上调和性别依赖性差异以及Sox 9基因表达的性别依赖性差异可能是值得注意的发现。
Genetic polydactyly/arhinencephaly mouse embryo, Pdn/Pdn, exhibits suppression of Gli3 gene expression. Ochratoxin A (OTA) is a teratogen that causes neural tube defects (NTD) in mice. We investigated gender‐dependent differences in the incidence of NTD induced by OTA in the Pdn/Pdn mouse. After administering 2 mg/kg OTA to Pdn/+ female mice, mated with Pdn/+ males, on day 7.5 of gestation, we examined the genotypes, sex and NTD of fetuses on day 18. Non‐treated Pdn/Pdn had a 15.8% risk of NTD, and all NTD fetuses were female. When Pdn/Pdn embryos were exposed to OTA, the incidence of NTD increased to 16 (51.6%) of 31 Pdn/Pdn fetuses, and 10 (71.4%) of 14 male Pdn/Pdn fetuses exhibited NTD. From these results, it was speculated that NTD in OTA‐treated male Pdn/Pdn were due to the synergistic effect between depressed Gli3 and altered sex‐correlated gene expression from OTA treatment. After treatment with OTA, the embryos were recovered on day 9 and gene expressions, which were correlated with Gli3, telencephalic morphogenesis, formation of gonadal anlage, and gender‐dependent differentiation were investigated. From real‐time polymerase chain reaction analysis results, it was suggested that the manifestation of NTD in the male OTA‐treated Pdn/Pdn might be due to the complicated altered gene expressions among Gli3, Wnt7b, Wnt8b, Fez1, Barx1, Lim1, Dmrt1, Igf1, Fog2, Dax1 and Sox9, and in particular, upregulation and gender‐dependent difference in Barx1 and gender‐dependent difference in Sox9 gene expressions might be noteworthy findings.
DOI：
10.1002/bdra.20511
发表时间：
2008-10
影响因子：
--
作者：
Deak, Kristen L.;Siegel, Deborah G.;George, Timothy M.;Gregory, Simon;Ashley-Koch, Allison;Speer, Marcy C.
通讯作者：
Speer, Marcy C.
影响因子：
1.2
作者：
Kim, SS;Kettlewell, JR;Zarkower, D
通讯作者：
Zarkower, D