Effect of heme oxygenase-1 deficiency on placental development.
Effect of heme oxygenase-1 deficiency on placental development.
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DOI：
10.1016/j.placenta.2009.07.012
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发表时间：
2009-10
期刊：
影响因子：
3.8
通讯作者：
Stevenson, D. K.
中科院分区：
文献类型：
--
作者：
Zhao, H.;Wong, R. J.;Kalish, F. S.;Nayak, N. R.;Stevenson, D. K.
关键词：
血红素氧酶（HO）是血红素分解代谢途径中的限制酶，在plapiTA中高度表达HO-1中的缺乏症。和e宾氏症的目的。 HO-1 +/-）小鼠杂交，纯合子（MUT，HO-1 - / - ）后代（2.4％）的出生率极低，并且观察到小垃圾大小。相对较小，体重小于E12.5和E15.5的野生型（WT）杂交的体重。有趣的是，在HO-2上，构成性HO同工型以及iNOS和eNOS表达的差异显着更新。 wt plecetas并似乎是由于凋亡的增加。 HET胎盘，特别是在海绵素细胞层中。孕妇舒张压和血浆SFLT-1水平的变化以及HO-2表达的补偿性增加。
Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway and highly expressed in the placenta. Deficiencies in HO-1, the inducible isoform, have been associated with pregnancy disorders, such as recurrent miscarriages, intrauterine growth retardation, and pre-eclampsia. The aim of this study was to identify if a deficiency in HO-1 affects placental development using a mouse model. When HO-1 heterozygote (Het, HO-1+/−) mice were cross-bred, an extremely low birth rate in homozygote (Mut, HO-1−/−) offspring (2.4%) and small litter sizes were observed. Placentas and fetuses from Het cross-breedings were relatively smaller and weighed less than those from wild-type (WT) cross-breedings at E12.5 and E15.5. Furthermore, Het placentas had significantly less HO-1 mRNA and protein levels than WT placentas, but no significant differences in placental HO activity. Interestingly, HO-2, the constitutive HO isoform, as well as iNOS and eNOS expression were significantly upregulated in Het placentas. Histological examination showed that the junctional zone (JZ) of Het placentas were markedly thinner than those of WT placentas and appeared to be due to an increase in apoptosis. Immunohistochemistry revealed that HO-1-expressing cells were located primarily in the JZ of Het placentas, specifically in the spongiotrophoblast layer. In addition, diastolic blood pressures and plasma soluble VEGFR-1 (sFlt-1) levels were significantly elevated in pregnant Het mice. We conclude that a partial deficiency in HO-1 is associated with morphological changes in the placenta and elevations in maternal diastolic blood pressure and plasma sFlt-1 levels, despite a compensatory increase in HO-2 expression.
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