The placenta: transcriptional, epigenetic, and physiological integration during development - PubMed (original) (raw)

Review

. 2010 Apr;120(4):1016-25.

doi: 10.1172/JCI41211. Epub 2010 Apr 1.

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Review

The placenta: transcriptional, epigenetic, and physiological integration during development

Emin Maltepe et al. J Clin Invest. 2010 Apr.

Abstract

The placenta provides critical transport functions between the maternal and fetal circulations during intrauterine development. Formation of this interface relies on coordinated interactions among transcriptional, epigenetic, and environmental factors. Here we describe these mechanisms in the context of the differentiation of placental cells (trophoblasts) and synthesize current knowledge about how they interact to generate a functional placenta. Developing an understanding of these pathways contributes to an improvement of our models for studying trophoblast biology and sheds light on the etiology of pregnancy complications and the in utero programming of adult diseases.

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Figures

Figure 1

Figure 1. Comparative anatomy of human and mouse placentas.

Placentation is categorized by the relationship between trophoblasts and the maternal cells/tissues with which they come into contact. In the hemochorial placentas of humans (A–C) and mice (D–F), the maternal vessels are invaded and colonized by invasive trophoblasts (not shown). (A) Consequently, in humans, decidual spiral arterioles perfuse the chorionic villi that line the intervillous space (adapted from PLoS Pathogens; ref. 158). (B) In floating villi (FV), a continuous layer of multinucleated SynT interfaces with maternal blood. Beneath lies a progenitor population of mononuclear vCTB. At the uterine wall, iCTBs differentiate along the invasive pathway to form anchoring villi (AV). A subset of iCTBs breaches spiral arterioles and differentiates into an endovascular subtype that replaces the resident maternal endothelium (not shown). (C) The cross-sectional anatomy of a floating villus shows that the apical surfaces of SynTs are covered with branched microvilli that maximize their surface areas for gas and nutrient/waste exchange. The blood vessels that ramify through the villous stroma carry embryonic/fetal blood. (D) In mice, maternal blood from decidual spiral arterioles flows through blood sinuses in the SpT layer to reach the labyrinth. (E) TGCs, like iCTBs, anchor the placenta to the uterus and invade the spiral arterioles (not shown). (F) In mice, maternal blood is in direct contact with a layer of mononuclear trophoblasts (MNTs, also known as S-TGCs) that is surrounded by a bilayer of SynTs, which are in close proximity to fetal capillaries.

Figure 2

Figure 2. Lineage segregation within the mouse blastocyst and early placenta.

(A) At day E3.5, the blastocyst comprises an outer TE destined to populate the placenta and an ICM destined to form the embryo. TE cells not in direct contact with the ICM form the mural TE, whereas those adjacent to the ICM form the polar TE. The polar TE gives rise to the ExE, from which TS cells can be derived in vitro. (B) Following implantation, mural TEs initiate the first wave of TGC differentiation to form 1° TGCs, which contribute directly to the P-TGC population. Cells within the polar TE continue to proliferate and populate the ExE. Some 2° TGCs arise directly from the ExE. Along with 1° TGCs, they compose the P-TGC population that lines the implantation site. Cells within the ExE then differentiate to form the chorionic plate and the EPC. The chorionic plate is responsible for populating the mouse labyrinth with SynTs and a subset of 2° TGCs called S-TGCs. Together, these cells are responsible for the transport functions of the placenta. Cells within the EPC can either differentiate into a population of lineage-committed progenitors known as SpTs, which then differentiate into 2° TGCs, or they can directly differentiate into various 2° TGCs subtypes.

Figure 3

Figure 3. Transcriptional and epigenetic regulation of trophoblast lineage restriction in the mouse.

Critical transcriptional regulators are highlighted in green, and epigenetic regulators are highlighted in blue. Undifferentiated ES cells are depicted on the left along with known transcriptional and epigenetic regulators responsible for the maintenance of stemness in mouse ES cells. TS cells are depicted on the right along with the differentiation pathways that give rise to lineage-committed progenitors (CTs and SpTs) as well as the terminally differentiated cells of the placenta (multinucleated SynTs and TGCs). The factors necessary for the derivation or maintenance of TS cells are indicated along with factors that operate in a lineage- and stage-specific manner.

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