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In both adult human and canine, the cardiac right ventricle (RV) is known to exhibit a peristaltic-like motion, where RV sinus (inflow region) contracts first and the infundibulum (outflow region) later, in a wave-like contraction motion. The delay in contraction between the sinus and infundibulum averaged at 15% of the cardiac cycle and was estimated to produce an intra-ventricular pressure difference of 15 mmHg. However, whether such a contractile motion occurs in human fetuses as well, its effects on hemodynamics remains unknown, and are the subject of the current study. Hemodynamic studies of fetal hearts are important as previous works showed that healthy cardiac development is sensitive to fluid mechanical forces. We performed 4D clinical ultrasound imaging on eight 20-weeks old human fetuses. In five fetal RVs, peristaltic-like contractile motion from the sinus to infundibulum ("forward peristaltic-like motion") was observed, but in one RV, peristaltic-like motion was observed from the infundibulum to sinus ("reversed peristaltic-like motion"), and two RVs contraction delay could not be determined due to poor regression fit. Next, we performed dynamic-mesh computational fluid dynamics simulations with varying extents of peristaltic-like motions for three of the eight RVs. Results showed that the peristaltic-like motion did not affect flow patterns significantly, but had significant influence on energy dynamics: increasing extent of forward peristaltic-like motion reduced the energy required for movement of fluid out of the heart during systolic ejection, while increasing extent of reversed peristaltic-like motion increased the required energy. It is currently unclear whether the peristaltic-like motion is an adaptation to reduce physiological energy expenditure, or merely an artefact of the cardiac developmental process.

During gestation the developing human fetus is exposed to a diverse range of potentially immune-stimulatory molecules including semi-allogeneic antigens from maternal cells, substances from ingested amniotic fluid, food antigens, and microbes. Yet the capacity of the fetal immune system, including antigen-presenting cells, to detect and respond to such stimuli remains unclear. In particular, dendritic cells, which are crucial for effective immunity and tolerance, remain poorly characterized in the developing fetus. Here we show that subsets of antigen-presenting cells can be identified in fetal tissues and are related to adult populations of antigen-presenting cells. Similar to adult dendritic cells, fetal dendritic cells migrate to lymph nodes and respond to toll-like receptor ligation; however, they differ markedly in their response to allogeneic antigens, strongly promoting regulatory T-cell induction and inhibiting T-cell tumour-necrosis factor-α production through arginase-2 activity. Our results reveal a previously unappreciated role of dendritic cells within the developing fetus and indicate that they mediate homeostatic immune-suppressive responses during gestation.

The mechanics of intracardiac blood flow and the epigenetic influence it exerts over the heart function have been the subjects of intense research lately. Fetal intracardiac flows are especially useful for gaining insights into the development of congenital heart diseases, but have not received due attention thus far, most likely because of technical difficulties in collecting sufficient intracardiac flow data in a safe manner. Here, we circumvent such obstacles by employing 4D STIC ultrasound scans to quantify the fetal heart motion in three normal 20-week fetuses, subsequently performing 3D computational fluid dynamics simulations on the left ventricles based on these patient-specific heart movements. Analysis of the simulation results shows that there are significant differences between fetal and adult ventricular blood flows which arise because of dissimilar heart morphology, E/A ratio, diastolic-systolic duration ratio, and heart rate. The formations of ventricular vortex rings were observed for both E- and A-wave in the flow simulations. These vortices had sufficient momentum to last until the end of diastole and were responsible for generating significant wall shear stresses on the myocardial endothelium, as well as helicity in systolic outflow. Based on findings from previous studies, we hypothesized that these vortex-induced flow properties play an important role in sustaining the efficiency of diastolic filling, systolic pumping, and cardiovascular flow in normal fetal hearts.

The National Academies of Sciences and Medicine 2020 consensus statement advocates the reinstatement of research in preconception heritable human genome editing (HHGE), despite the ethical concerns that have been voiced about interventions in the germline, and outlines criteria for its eventual clinical application to address monogenic disorders. However, the statement does not give adequate consideration to alternative technologies. Importantly, it omits comparison to fetal gene therapy (FGT), which involves gene modification applied prenatally to the developing fetus and which is better researched and less ethically contentious. While both technologies are applicable to the same monogenic diseases causing significant prenatal or early childhood morbidity, the benefits and risks of HHGE are distinct from FGT though there are important overlaps. FGT has the current advantage of a wealth of robust preclinical data, while HHGE is nascent technology and its feasibility for specific diseases still requires scientific proof. The ethical concerns surrounding each are unique and deserving of further discussion, as there are compelling arguments supporting research and eventual clinical translation of both technologies. In this Opinion, we consider HHGE and FGT through technical and ethical lenses, applying common ethical principles to provide a sense of their feasibility and acceptability. Currently, FGT is in a more advanced position for clinical translation and may be less ethically contentious than HHGE, so it deserves to be considered as an alternative therapy in further discussions on HHGE implementation. [ABSTRACT FROM AUTHOR]