Sexually dimorphic gene expression that overlaps maturation of type II pneumonocytes in fetal mouse lungs.

Sexually dimorphic gene expression that overlaps maturation of type II pneumonocytes in fetal mouse lungs.
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DOI:
10.1186/1477-7827-4-25
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发表时间:
2006-05-04
期刊:
Reproductive biology and endocrinology : RB&E
影响因子:
--
通讯作者:
Tremblay Y
Tremblay Y
中科院分区:
其他
文献类型:
--
作者:
Simard M;Provost PR;Tremblay Y

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在人类中,早产儿发生的新生儿呼吸窘迫多见于男性。在妊娠晚期,男性胎儿的II型肺泡上皮细胞的成熟,以及随后的表面活性物质合成高峰比女性胎儿延迟。尽管男性胎儿体内较高水平的雄激素被认为可以解释这种性别差异,但参与肺成熟的基因是否根据胎儿性别进行了不同的调节,目前尚不清楚。我们通过基因图谱研究了在成熟的PTII细胞出现之前的三天妊娠窗口期内小鼠肺发育的性别差异(小鼠肺表面活性物质合成高峰出现在GD17.5)。从孕15.5天、16.5天和17.5天的雄性和雌性胎鼠肺中提取总RNA,转化为cRNA,生物素标记,与寡核苷酸芯片(Affymetrix MOE430A)杂交。使用MAS5.0、LFCM和Genesis软件进行数据分析。许多参与肺成熟的基因表达没有性别差异。在这些阵列覆盖的大约14000个转录本中,只有83个基因在GDS 15.5和17.5之间的一个或多个时间点出现了性别差异。它们包括与激素代谢和调节(即类固醇生成途径)、细胞凋亡、信号转导、转录调节和脂代谢有关的基因,其中包括四个载脂蛋白基因。涉及免疫功能和其他新陈代谢的基因也显示出性别差异。在这些性二态基因中,有些可能是参与肺成熟的候选基因。事实上,在GD17.5上,表面活性物质脂类的性别差异与参与脂质运输的载脂蛋白基因在肺内表达的性别差异相关。这表明这些基因在表面活性物质合成的激增中发挥了作用。我们的结果将有助于识别与新生儿呼吸窘迫的生理病理有关的新基因。
In human, respiratory distress of the neonates, which occurs in prematurity, is prevalent in male. Late in gestation, maturation of type II pneumonocytes, and consequently the surge of surfactant synthesis are delayed in male fetuses compared with female fetuses. Although the presence of higher levels of androgens in male fetuses is thought to explain this sex difference, the identity of genes involved in lung maturation that are differentially modulated according to fetal sex is unknown. We have studied the sex difference in developing mouse lung by gene profiling during a three-day gestational window preceding and including the emergence of mature PTII cells (the surge of surfactant synthesis in the mouse occurs on GD 17.5). Total RNA was extracted from lungs of male and female fetal mice (gestation days 15.5, 16.5, and 17.5), converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays (Affymetrix MOE430A). Analysis of data was performed using MAS5.0, LFCM and Genesis softwares. Many genes involved in lung maturation were expressed with no sex difference. Of the approximative 14 000 transcripts covered by the arrays, only 83 genes presented a sex difference at one or more time points between GDs 15.5 and 17.5. They include genes involved in hormone metabolism and regulation (i.e. steroidogenesis pathways), apoptosis, signal transduction, transcriptional regulation, and lipid metabolism with four apolipoprotein genes. Genes involved in immune functions and other metabolisms also displayed a sex difference. Among these sexually dimorphic genes, some may be candidates for a role in lung maturation. Indeed, on GD 17.5, the sex difference in surfactant lipids correlates with the sex difference in pulmonary expression of apolipoprotein genes, which are involved in lipid transport. This suggests a role for these genes in the surge of surfactant synthesis. Our results would help to identify novel genes involved in the physiopathology of the respiratory distress of the neonates.
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影响因子: 4.8
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发表时间: 1995-01-01
影响因子: 6.4
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影响因子: 14.2
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