Outhwaite Jennifer E, Patel Jatin, Simmons David G
Faculty of Medicine, School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, Australia.
Translational Research Institute, UQ Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.
Front Physiol. 2019 May 29;10:622. doi: 10.3389/fphys.2019.00622. eCollection 2019.
The Coxsackie virus and adenovirus receptor (CXADR) is an adhesion molecule known for its role in virus-cell interactions, epithelial integrity, and organogenesis. Loss of causes numerous embryonic defects in mice, notably abnormal development of the cardiovascular system, and embryonic lethality. While CXADR expression has been reported in the placenta, the precise cellular localization and function within this tissue are unknown. Since impairments in placental development and function can cause secondary cardiovascular abnormalities, a phenomenon referred to as the placenta-heart axis, it is possible placental phenotypes in mutant embryos may underlie the reported cardiovascular defects and embryonic lethality. In the current study, we determine the cellular localization of placental expression and whether there are placental abnormalities in the absence of . In the placenta, CXADR is expressed specifically by trophoblast labyrinth progenitors as well as cells of the visceral yolk sac (YS). In the absence of , we observed altered expression of angiogenic factors coupled with poor expansion of trophoblast and fetal endothelial cell subpopulations, plus diminished placental transport. Unexpectedly, preserving endogenous trophoblast expression revealed the placental defects to be secondary to primary embryonic and/or YS phenotypes. Moreover, further tissue-restricted deletions of suggest that the secondary placental defects are likely influenced by embryonic lineages such as the fetal endothelium or those within the extraembryonic YS vascular plexus.
柯萨奇病毒和腺病毒受体（CXADR）是一种黏附分子，因其在病毒 - 细胞相互作用、上皮完整性和器官发生中的作用而闻名。CXADR缺失会在小鼠中导致众多胚胎缺陷，尤其是心血管系统发育异常以及胚胎致死。虽然已有报道称CXADR在胎盘中表达，但其在该组织内的确切细胞定位和功能尚不清楚。由于胎盘发育和功能受损可导致继发性心血管异常，即所谓的胎盘 - 心脏轴现象，因此CXADR突变胚胎中的胎盘表型可能是所报道的心血管缺陷和胚胎致死的基础。在本研究中，我们确定了胎盘CXADR表达的细胞定位以及在CXADR缺失时是否存在胎盘异常。在胎盘中，CXADR由滋养层迷路祖细胞以及脏壁卵黄囊（YS）细胞特异性表达。在CXADR缺失的情况下，我们观察到血管生成因子表达改变，并伴有滋养层和胎儿内皮细胞亚群的增殖不良以及胎盘转运减少。出乎意料的是，保留内源性滋养层CXADR表达显示胎盘缺陷继发于原发性胚胎和/或YS表型。此外，CXADR进一步的组织限制性缺失表明，继发性胎盘缺陷可能受胚胎谱系影响，如胎儿内皮或胚外YS血管丛内的谱系。
