Sarkar Anjali A, Sabatino Julia A, Sugrue Kelsey F, Zohn Irene E
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA; Institute for Biomedical Sciences, The George Washington University, Washington, DC 20052, USA.
Placenta. 2016 Feb;38:16-23. doi: 10.1016/j.placenta.2015.12.002. Epub 2015 Dec 13.
The labyrinthine zone of the placenta is where exchange of nutrients and waste occurs between maternal and fetal circulations. Proper development of the placental labyrinth is essential for successful growth of the developing fetus and abnormalities in placental development are associated with intrauterine growth restriction (IUGR), preeclampsia and fetal demise. Our previous studies demonstrate that Hectd1 is essential for development of the junctional and labyrinthine zones of the placenta. Here we further characterize labyrinthine zone defects in the Hectd1 mutant placenta.
The structure of the mutant placenta was compared to wildtype littermates using histological methods. The expression of cell type specific markers was examined by immunohistochemistry and in situ hybridization.
Hectd1 is expressed in the labyrinthine zone throughout development and the protein is enriched in syncytiotrophoblast layer type I cells (SynT-I) and Sinusoidal Trophoblast Giant cells (S-TGCs) in the mature placenta. Mutation of Hectd1 results in pale placentas with frequent hemorrhages along with gross abnormalities in the structure of the labyrinthine zone including a smaller overall volume and a poorly elaborated fetal vasculature that contain fewer fetal blood cells. Examination of molecular markers of labyrinthine trophoblast cell types reveals increased Dlx3 positive cells and Syna positive SynT-I cells, along with decreased Hand1 and Ctsq positive sinusoidal trophoblast giant cells (S-TGCs).
Together these defects indicate that Hectd1 is required for development of the labyrinthine zonethe mouse placenta.
胎盘的迷路区是母体和胎儿循环之间进行营养物质交换和废物排出的部位。胎盘迷路的正常发育对于发育中胎儿的成功生长至关重要，胎盘发育异常与宫内生长受限（IUGR）、先兆子痫和胎儿死亡有关。我们之前的研究表明，Hectd1对于胎盘绒毛叶和迷路区的发育至关重要。在此，我们进一步描述Hectd1突变胎盘迷路区的缺陷。
使用组织学方法将突变胎盘的结构与野生型同窝仔进行比较。通过免疫组织化学和原位杂交检测细胞类型特异性标志物的表达。
Hectd1在整个发育过程中均在迷路区表达，在成熟胎盘中，该蛋白在合体滋养层I型细胞（SynT-I）和窦状滋养层巨细胞（S-TGCs）中富集。Hectd1突变导致胎盘苍白，伴有频繁出血，同时迷路区结构出现明显异常，包括总体积较小以及胎儿血管系统发育不良，其中胎儿血细胞较少。对迷路滋养层细胞类型的分子标志物进行检测发现，Dlx3阳性细胞和Syna阳性的SynT-I细胞增加，而Hand1和Ctsq阳性的窦状滋养层巨细胞（S-TGCs）减少。
这些缺陷共同表明，Hectd1是小鼠胎盘迷路区发育所必需的。
