The role of chorionic cytotrophoblasts in the smooth chorion fusion with parietal decidua

Abstract

Background/purpose: Human placenta and chorion are rapidly growing transient embryonic organs built from diverse cell populations that are of either, ectodermal [placenta and chorion specific trophoblast (TB) cells], or mesodermal origin [villous core and chorionic mesenchyme]. The development of placenta and chorion is synchronized from the earliest phase of implantation. Little is known about the formative stages of the human chorion, in particular the steps between the formation of a smooth chorion and its fusion with the parietal decidua.

Methods: We examined the available histological material using immunohistochemistry, and further analyzed in vitro the characteristics of the recently established and reported human self-renewing trophoblast progenitor cells (TBPC) derived from chorionic mesoderm.

Results: Here, we provided evidence that the mechanism by which smooth chorion fuses with parietal decidua is the invasion of smooth chorionic cytotrophoblasts (schCTBs) into the uterine wall opposite to the implantation side. This process, which partially replicates some of the mechanisms of the blastocyst implantation, leads to the formation of a new zone of contacts between fetal and maternal cells.

Conclusion: We propose the schCTBs invasion of the parietal decidua as a mechanism of 'fusion' of the membranes, and that schCTBs in vivo contribute to the pool of the invasive schCTB.

Keywords: Chorionic cytotrophoblast; Human pregnancy; Invasive CTBs; Smooth chorion; Trophoblast progenitor cells.

Figure 1. Early human embryo development

Hematoxylin and eosin staining of day 15 pc implantation site shows the embedded blastocyst. bd bilaminar disk, mc mesenchyme, ctbs cytotrophoblast, dec decidua, ue uterine epitethelium. Tissue sections graciously provided and printed with the permission of Dr. Jelena Lazic from the Clinic of Obstetrics and Gynecology, University of Belgrade, Serbia.

Figure 2. Schematic illustration of the pregnant uterus

Depiction of the developing fetus and associated membranes between 16–18 weeks of pregnancy (A) and at term (B). After chorionic fusion with parietal decidua the uterine epithelium lining that covers the capsular and parietal decidua is indistinguishable and schCTBs are embedded in the stroma of the parietal decidua. A 1 amniotic epithelium, 2 amniotic/chorionic mesoderm, 3 smooth chorion cytotrophoblasts, 4 capsular decidua, 5 uterine epithelium covering capsular decidua, 6 uterine cavity, 7 uterine epithelial lining of the paretial decidua, 8 parietal decidua B 1 amniotic epithelium, 2a amniotic mesoderm, 2b chorionic mesoderm, 3 smooth chorion CTBs, 4 parietal decidua

Figure 3. Smooth chorion cytotrophoblast share the same trophoblast fate determinants with invasive cytotrophoblasts from the placental bed

Immunostaining of 20.3 weeks of gestation smooth chorion (A, C) and the basal plate (B, D) tissue sections, demonstrates that, during the invasion into decidual stroma, schCTBs up-regulate HLA-G (A, B) and integrin α4 (C, D) markers of iCTBs. Nuclei are stained with DAPI in blue. ae amniotic epithelium, mc mesenchyme, iCTBs invasive cytotrophoblast, schCTBs smooth chorion cytotrophoblasts, dec decidua, ck7 cytokeratin 7.

Figure 4. Smooth chorion cytotrophoblast (schCTB) invasion

SchCTBs deeply invade the decidua stroma at 20 weeks of pregnancy. The arrow indicates invasion of schCTBs, identified by the expression of cytokeratin 7 (CK7), into parietal decidua. Nuclei are stained with DAPI in blue. ae amniotic epithelium, mc mesenchyme, schCTBs smooth chorion cytotrophoblasts, p.dec parietal decidua.

Figure 5. Trophoblast progenitor cell (TBPC) subpopulation reside in the mesoderm of the smooth chorion

Immunostaining of smooth chorion reveals, in the chorionic mesoderm, the presence of HMGA2, integrin α4 and HLA-G positive TBPCs (Fig A–D). A subpopulation of cytokeratin 7 (CK7) positive smooth chorion cytotrophoblasts co-express integrin α4 (A) and HLA-G (C). Panels B and D are enlarged images of the areas highlighted with rectangle in panels A and C respectively. Nuclei are stained with DAPI in blue.

Figure 6. Schematic representation of the model proposed for the in vivo role of trophoblast progenitor cells

Smooth chorion during first trimester of pregnancy (A) and second trimester of pregnancy (B). CSC chorionic stem cells, TBPC trophoblast progenitor cells, iCTB invasive cytotrophoblasts, schCTB smooth chorion cytotrophoblasts, ischCTB invasive smooth chorion cytotrophoblasts