Iqbal Khursheed, Nixon Brandon, Crnkovich Benjamin, Dominguez Esteban M, Moreno-Irusta Ayelen, Scott Regan L, Vu Ha T H, Tuteja Geetu, Vivian Jay L, Soares Michael J
bioRxiv. 2023 Aug 5:2023.08.02.551740. doi: 10.1101/2023.08.02.551740.
Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade into the uterus where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome editing techniques. In this investigation, we generated a conditional rat model targeting the invasive trophoblast cell lineage. Prolactin family 7, subfamily b, member 1 ( ) is uniquely and abundantly expressed in the rat invasive trophoblast cell lineage. Disruption of did not adversely affect placental development. We demonstrated that the locus could be effectively used to drive the expression of Cre recombinase in invasive trophoblast cells. Our rat model represents a new tool for investigating candidate genes contributing to the regulation of invasive trophoblast cells and their contributions to trophoblast-guided uterine spiral artery remodeling.
胎盘发育涉及具有特定功能的滋养层细胞谱系的协调扩张和分化。分化的滋养层细胞谱系中包括侵入性滋养层细胞,这些细胞离开胎盘并侵入子宫,在那里它们重塑子宫实质并促进子宫螺旋动脉的重塑。大鼠表现出深度的子宫内滋养层细胞侵袭,这是与人类胎盘形成共有的特征,并且也适用于使用基因组编辑技术进行基因操作。在本研究中,我们生成了一个针对侵入性滋养层细胞谱系的条件性大鼠模型。催乳素家族7,亚家族b,成员1( )在大鼠侵入性滋养层细胞谱系中独特且大量表达。对 的破坏并未对胎盘发育产生不利影响。我们证明 基因座可有效地用于驱动Cre重组酶在侵入性滋养层细胞中的表达。我们的大鼠模型代表了一种新工具,用于研究有助于调节侵入性滋养层细胞的候选基因及其对滋养层引导的子宫螺旋动脉重塑的贡献。