Development of the Human Placenta and Fetal Heart: Synergic or Independent?

Abstract

The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c.) give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12-14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces smooth muscle cells surrounding the placental arteries to dedifferentiate and adopt a proliferative phenotype. This change is associated with increased umbilical resistance measured by Doppler ultrasound, and is likely to exert a major effect on the developing heart through the afterload. Thus, both the umbilical and maternal placental circulations may impact on development of the heart.

Keywords: congenital heart disease; fetal heart; placenta; pregnancy; umbilical circulation; vascular resistance.

Figure 1

The extravillous circulations. The yolk sac is the first of the extraembryonic membranes to be vascularized, and likely plays a key role in maternal-fetal transport during the period of organogenesis before the chorionic circulation is fully established at ~12 weeks. Changes in the resistance offered by each circulation may affect gene expression and differentiation of the fetal cardiomyocytes. From Burton et al. (2016) with permission.

Figure 2

Development of the placental vasculature. (A) Placental villi of 6 weeks gestational age prior to onset of the chorionic circulation, showing the presence of nucleated erythrocytes in the developing fetal capillaries (arrowed). (B) Villi at 14 weeks gestational age showing the presence of non-nucleated erythrocytes in the larger vessels within the stromal core, indicative of onset of the chorionic circulation. (C) Villi of 27 weeks gestational age. By now the smaller peripheral villi are being elaborated. (D) Villi of 40 weeks gestational age showing well vascularized terminal villi. Scale bar for all images = 50 μm. Stain; haematoxylin and eosin for all.

Figure 3

Color Doppler mapping of the utero-placental circulation at 7 weeks 2 days of gestation showing the absence of circulation within the placenta (P). ECC, exocoleomic cavity; F, Fetus.

Figure 4

Flow velocity waveforms from the umbilical artery at 10 weeks and 6 days showing the absence of end-diastolic flow in all cardiac cycles.

Figure 5

Flow velocity waveforms from the umbilical artery at 13 weeks and 1 day showing partial end-diastolic flow. In some cardiac cycles there is flow throughout almost the entire diastolic phase, indicating a reduction in vascular resistance in the umbilico-placental vascular bed.