Human placental oxygenation in late gestation: experimental and theoretical approaches

Abstract

The placenta is crucial for life. It is an ephemeral but complex organ acting as the barrier interface between maternal and fetal circulations, providing exchange of gases, nutrients, hormones, waste products and immunoglobulins. Many gaps exist in our understanding of the detailed placental structure and function, particularly in relation to oxygen handling and transfer in healthy and pathological states in utero. Measurements to understand oxygen transfer in vivo in the human are limited, with no general agreement on the most appropriate methods. An invasive method for measuring partial pressure of oxygen in the intervillous space through needle electrode insertion at the time of Caesarean sections has been reported. This allows for direct measurements in vivo whilst maintaining near normal placental conditions; however, there are practical and ethical implications in using this method for determination of placental oxygenation. Furthermore, oxygen levels are likely to be highly heterogeneous within the placenta. Emerging non-invasive techniques, such as MRI, and ex vivo research are capable of enhancing and improving current imaging methodology for placental villous structure and increase the precision of oxygen measurement within placental compartments. These techniques, in combination with mathematical modelling, have stimulated novel cross-disciplinary approaches that could advance our understanding of placental oxygenation and its metabolism in normal and pathological pregnancies, improving clinical treatment options and ultimately outcomes for the patient.

Keywords: FGR; MRI; intervillious space; modelling; oxygen; perfusion; placenta.

Figure 1. Simplified schematic diagram of the maternal and fetal placental circulations, showing the major compartments and published attributed in vivo oxygen values (see Table 1)

Figure 2. Measuring oxygen distribution in the human placenta

A, demonstrating a normal placenta imaged using oxygen‐enhanced (OE) MRI techniques. This shows an axial T2‐weighted structural MR image through maternal abdomen at the level of the uterine cavity (circled in blue) demonstrating: fetal abdominal cross‐section (circled in white) and placental region of interest (circled in red) with a superimposed delta R1 map. The colour gradient voxels in the dR1 map demonstrate the differing change in $P_{{\mathrm{O}}_2}$ across the placenta following maternal hyperoxia. B, soluble oxygen measurement of the perfusate in the maternal‐side arterial inflow line and the IVS in the ex vivo dually perfused placental lobule, measured via a pre‐IVS oxygen chamber (flow‐through cell) and via an optode needle inserted into the placental tissue, respectively. C, a close‐up image showing the insertion points of both the maternal cannula (i.d. = 2 mm, super‐glued into position to form a seal with the decidua) and the IVS oxygen optode needle inserted through the decidual surface of the placenta.

Figure 3. Evaluating imaging techniques for use in assessing placental structure

A, a transmission electron micrograph of terminal villi showing microvillous membrane (MVM), an underlying capillary (CAP), a syncytiotrophoblast (S), a trophoblast (T) and endothelium (E). B, projection of an imaged stack (wholemount confocal microscopy), stained with lectin FITC‐AAL for the endothelium (green), rhodamine‐PSA for the stroma (red) and biotin‐DSL for the trophoblast (violet); the DSL was detected with streptavidin 680 and imaging was on a Leica Sp5 confocal microscope, presented as an image stack. C, villous microcirculation of a term normal placenta perfused with a Ulex Europaeus Agglutinin (UEA) lectin linked to biotin and detected with streptavidin 800. D, microCT image of a vascular corrosion cast of a term placenta, infused through the umbilical artery with Batson's resin, which was then set, followed by tissue corrosion steps for several days in 20% (w/v) potassium hydroxide.

Figure 4. Mathematical modelling of human placental perfusion and oxygenation at different scales

A, variability of perfusion in a fetoplacental vascular network (colour scale shows pressure for chorionic vessels and relative capillary flow for terminal capillaries, plotted as spheres) (Clark et al. 2015). B, distribution of a passive solute in the intervillous space of a single placental lobule (Chernyavsky et al. 2010). C, oxygen flux distribution over the capillary and syncytiotrophoblast surfaces of a single terminal villus (Pearce et al. 2016). D, microscopic flow in the intervillous space (Perazzolo et al. 2017). Images are reproduced with permission, subject to the respective copyrights.