Proctor L K, Dunk C, Baczyk D, Kingdom J C P, Adamson S Lee
Samuel Lunenfeld Research Institute, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, and Department of Physiology, University of Toronto, Toronto, Ontario, Canada.
Placenta. 2009 Jan;30(1):96-104. doi: 10.1016/j.placenta.2008.09.014. Epub 2008 Nov 12.
In mice the exchange of oxygen and nutrients between mother and fetus occurs in the chorioallantoic placenta where fetal capillaries come in close proximity with maternal blood perfusing trophoblast-lined sinusoids. Despite its critical importance, quantitative in vivo gene expression over the initial stages of chorioallantoic placental development has not been described, nor are there in vitro systems recapitulating the critical syncytiotrophoblast differentiation step in its formation. Here we describe molecular events that occur during the onset of chorioallantoic morphogenesis in mice in vivo, and in placental explant and whole conceptus cultures in vitro.
Chorioallantoic morphogenesis began immediately following allantoic fusion with the chorion in vivo, and was associated with significant upregulation of syncytiotrophoblast associated mRNA (Gcm1 and Syncytin A). However mouse placentas with chorioallantoic point attachment cultured with the allantois or as whole conceptuses did not upregulate Gcm1 and/or Syncytin A, suggesting that syncytiotrophoblast differentiation did not occur in vitro. Failure of morphogenesis appeared to be due to failure to sustain in vitro the chorionic trophoblast cells from which the syncytiotrophoblast cells are derived. In vitro culture conditions did support the upregulation of ectoplacental cone marker Tpbpalpha, maintenance of giant cell marker Pl1, and maintenance of Fgfr2 expression; all of which mimicked in vivo events observed over this developmental interval.
We conclude that chorionic trophoblast maintenance and the early events that occur in vivo between chorioallantoic point attachment and primary villous formation are dependent on undefined intrauterine factors that were not present in the in vitro culture system. Nevertheless, in vitro culture conditions were appropriate to reproduce in vivo expression levels of Fgfr2, Pl1, and Tpbpalpha in placental explants.
在小鼠中,母体与胎儿之间的氧气和营养物质交换发生在绒膜尿囊胎盘,胎儿毛细血管与灌注滋养层内衬血窦的母体血液紧密相邻。尽管其至关重要,但尚未描述绒膜尿囊胎盘发育初始阶段的体内定量基因表达情况,也没有体外系统能够重现其形成过程中关键的合体滋养层分化步骤。在此,我们描述了小鼠体内绒膜尿囊形态发生开始时以及体外胎盘外植体和整个胚胎培养过程中发生的分子事件。
在体内,尿囊与绒毛膜融合后立即开始绒膜尿囊形态发生,并与合体滋养层相关mRNA(Gcm1和Syncytin A)的显著上调相关。然而,将带有绒膜尿囊附着点的小鼠胎盘与尿囊一起培养或作为整个胚胎培养时,Gcm1和/或Syncytin A并未上调,这表明合体滋养层分化未在体外发生。形态发生失败似乎是由于未能在体外维持合体滋养层细胞所源自的绒毛膜滋养层细胞。体外培养条件确实支持上调外胎盘锥标志物Tpbpalpha、维持巨细胞标志物Pl1以及维持Fgfr2表达;所有这些都模拟了在此发育间隔期观察到的体内事件。
我们得出结论,绒毛膜滋养层的维持以及在体内绒膜尿囊附着点与初级绒毛形成之间发生的早期事件依赖于体外培养系统中不存在的未明确的子宫内因素。然而,体外培养条件适合在胎盘外植体中重现Fgfr2、Pl1和Tpbpalpha在体内的表达水平。