When Does the Human Embryonic Heart Start Beating? A Review of Contemporary and Historical Sources of Knowledge about the Onset of Blood Circulation in Man

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Abstract

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the first human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the fourth post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19th century, but did not receive much recognition by embryologists.

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Developmental stages in human embryos: revised and new measurements.

F Muller, R O'Rahilly (2009)

The staging of human embryos, as distinct from seriation, depends on a morphological scheme devised by Streeter and completed by O'Rahilly, who proposed the term Carnegie stages. To avoid misconceptions and errors, and to place new findings in perspective, it is necessary to summarize the essentials of the Carnegie system: (1) Twenty-three stages cover the embryonic period, i. e. the first 8 postfertilizational weeks of development. (2) The system is based on internal as well as external features, and the use of only external criteria is subject to serious limitations. For example, precise delineation of stages 19-23 and of the embryonic-fetal transition depends on histological examination. (3) Prenatal measurements are not an integral component of the staging system, and hence a stage should never be assigned merely on the basis of embryonic length. A 20-mm embryo, for example, could belong to any of three stages. Measurements, however, are important for the assessment of age, and very few measurements are available for staged embryos. Presented here and based on accurate staging are the maximum diameter of the chorionic sac, the crown-heel length, the greatest length exclusive of the lower limbs, the biparietal diameter, the head circumference, the length of the hindbrain, the total length of the brain, and the lengths of the limbs as well as of their segments, including the foot length. (4) Prenatal ages are also not an integral part of the staging system and hence a stage should never be assigned merely on the basis of prenatal age. Ages, however, are of clinical importance and their estimate has been rendered more precise by accurate timing of fertilization followed by ultrasonography. Prenatal age is postfertilizational and hence some 2 weeks less than the postmenstrual interval. The term gestational age is ambiguous and should be discarded. Presented here is a new graph showing proposed estimates of age in relation to stages and based on current information. Copyright 2010 S. Karger AG, Basel.

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Circulation is established in a stepwise pattern in the mammalian embryo.

A D Koniski, James Palis, Mary McGrath … (2003)

To better understand the relationship between the embryonic hematopoietic and vascular systems, we investigated the establishment of circulation in mouse embryos by examining the redistribution of yolk sac-derived primitive erythroblasts and definitive hematopoietic progenitors. Our studies revealed that small numbers of erythroblasts first enter the embryo proper at 4 to 8 somite pairs (sp) (embryonic day 8.25 [E8.25]), concomitant with the proposed onset of cardiac function. Hours later (E8.5), most red cells remained in the yolk sac. Although the number of red cells expanded rapidly in the embryo proper, a steady state of approximately 40% red cells was not reached until 26 to 30 sp (E10). Additionally, erythroblasts were unevenly distributed within the embryo's vasculature before 35 sp. These data suggest that fully functional circulation is established after E10. This timing correlated with vascular remodeling, suggesting that vessel arborization, smooth muscle recruitment, or both are required. We also examined the distribution of committed hematopoietic progenitors during early embryogenesis. Before E8.0, all progenitors were found in the yolk sac. When normalized to circulating erythroblasts, there was a significant enrichment (20- to 5-fold) of progenitors in the yolk sac compared with the embryo proper from E9.5 to E10.5. These results indicated that the yolk sac vascular network remains a site of progenitor production and preferential adhesion even as the fetal liver becomes a hematopoietic organ. We conclude that a functional vascular system develops gradually and that specialized vascular-hematopoietic environments exist after circulation becomes fully established.

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HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta

Graham J Burton, Tereza Cindrova-Davies, Hong wa Yung … (2021)

Development of the human placenta takes place in contrasting oxygen concentrations at different stages of gestation, from ~20 mmHg during the first trimester rising to ~60 mmHg at the start of the second trimester before gradually declining to ~40 mmHg at term. In view of these changes, the early placenta has been described as ‘hypoxic’. However, placental metabolism is heavily glycolytic, supported by the rich supply of glucose from the endometrial glands, and there is no evidence of energy compromise. On the contrary, the trophoblast is highly proliferative, with the physiological low-oxygen environment promoting maintenance of stemness in progenitor populations. These conditions favour the formation of the cytotrophoblastic shell that encapsulates the conceptus and interfaces with the endometrium. Extravillous trophoblast cells on the outer surface of the shell undergo an epithelial-mesenchymal transition and acquire invasive potential. Experimental evidence suggests that these changes may be mediated by the higher oxygen concentration present within the placental bed. Interpreting in vitro data is often difficult, however, due to the use of non-physiological oxygen concentrations and trophoblast-like cell lines or explant models. Trophoblast is more vulnerable to hyperoxia or fluctuating levels of oxygen than to hypoxia, and some degree of placental oxidative stress likely occurs in all pregnancies towards term. In complications of pregnancy, such as early-onset pre-eclampsia, malperfusion generates high levels of oxidative stress, causing release of factors that precipitate the maternal syndrome. Further experiments are required using genuine trophoblast progenitor cells and physiological concentrations to fully elucidate the pathways by which oxygen regulates placental development.

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Author and article information

Journal

Journal ID (publisher-id): JCDDB4

Title: Journal of Cardiovascular Development and Disease

Abbreviated Title: JCDD

Publisher: MDPI AG

ISSN (Electronic): 2308-3425

Publication date Created: June 2022

Publication date (Electronic): June 09 2022

Volume: 9

Issue: 6

Page: 187

Article

DOI: 10.3390/jcdd9060187

PubMed ID: 35735816

SO-VID: 00267fdc-dc74-42e7-9b6b-a29a4e4869a6

License:

https://creativecommons.org/licenses/by/4.0/

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