The sentence “…a small number of fetal red blood cells are seen in the maternal blood circulation.” in the text book P309 triggered my thinking weather that is one of the reasons vivipara do not have nucleated red blood cell in their circulatory system. If large amount of nucleated blood cell in the mother’s blood occasionally contact with fetus’ blood, strong immune response will kill the fetus, so under selection, only individuals with enucleated erythrocytes can survive, I guess.
In order to test my hypothesis, I started searching for information. Firstly, I found camel and giraffe’ erythrocytes have nuclear by Google. I thought if there is evidence showing their placenta structures are different from other mammals to have less possibility of maternal and fetal blood mixing, which should be a support of my hypothesis. But later, after searched for some academic articles, I found it is wrong. “All are unique among mammals, because camel’s erythrocytes are biscuit- or wafer-shaped ovals, with very little volume, and having little packed volume in whole blood (only 27-28 %). The hypothesis that they throw back to the ancestral reptiles and other lower vertebrates seemed superficially obvious, and perhaps led to the error often published that camel erythrocytes are nucleated. In fact, they are anucleate, but are unusual and novel in vertebrates.” (Long, 2007)
Furthermore, I found a credible source meaning that enucleated erythrocytes are dominant in blood in all mammal individuals including all marsupials, placental mammals, Prototheria and monotremes. Meanwhile all known non-mammalian vertebrates, including fish, amphibian, reptiles and birds, have nucleated erythrocytes (Baskurta and Meiselman, 2010). But in certain conditions, some animals will change the amount of nucleated erythrocytes or enucleated erythrocytes in their blood. Some marsupials have some circulating nucleated red blood cells as adults (Stonehouse, 1977). “Occasionally, reptilian RBC lacking nuclei are observed. These are called ‘erythroplastids,’ and their extruded nuclei found in the plasma are referred to as ‘hematogones’” (Mauro, 1997). In fetuses with intrauterine growth restriction, higher nucleated red blood cell counts at birth and longer persistence of nucleated red blood cell count are observed. Evidence shows that metabolic acidemia is in charge of causing that (Baschat, et al., 1999). These facts seem to be refutes to my hypothesis. So I decided to focus on the differences of erythropoiesis between mammal and non-mammals.
Then, I first realized, in early stage of human embryos, blood cells are not only generated by marrow. “In developing embryos, blood formation occurs in aggregates of blood cells in the yolk sac, called blood islands. As development progresses, blood formation occurs in the spleen, liver and lymph nodes. When bone marrow develops, it eventually assumes the task of forming most of the blood cells for the entire organism. ” (From Wikipedia)
What’s more, the hepatic erythropoiesis will occur in adults when excessive bleeding happened and a lot of blood cell is needed in emergency. What interested me is hepatic erythropoiesis will generate nucleated red blood cell (Baschat, et al., 1999), different from marrow. Will there be some similarities between non-mammals nucleated red blood cell? The answer seems to be no. Some net users said birds’ bones are empty inside, so they do not have marrow. They generate their blood cell by division of mature blood cells as the erythrocytes are nucleated. These net users must misunderstand something that some of the birds’ bones have marrow, and the red blood cells are produced in the bone marrow. This picture shows which bones of pigeon are empty inside and which are filled with marrow.
(Ornithology, Avian Circulatory System)
Finally, I found one explanation about why mammals’ erythrocytes are enucleated but non-mammalian vertebrates have nucleated erythrocytes in the aspect of evolution. But this explanation do not convince me: “Mammals, which had developed an aerobic metabolism, emerged in the Triassic, when the oxygen content in the atmosphere was by approximately 50% lower than the current level and even lower than in the Jurassic period. A drastic decrease in the total content and percentage of oxygen in the Triassic was connected with the prevalence of arid conditions on the continents. Under these conditions, mammals got rid of the nuclei in erythrocytes (having obtained enucleate and biconcave cells, where the surface area of the contained hemoglobin was larger), which led to thinner capillaries, while the biconcave shape provided a larger exchange area. Birds, which originated from more advanced reptiles, had established powerful respiratory and circulatory systems and, since they emerged at the time when the oxygen content in the Earth atmosphere approached the present level, had no need to eliminate the nuclei from their erythrocytes.” (Gavrilov, 2013)
I am wondering, in the Triassic, new coming mammals are suffering low oxygen content, why reptiles at that time are not? Why the ancestors of birds do not get rid of the nuclei in erythrocytes in Triassic? In other words, most of us have no doubt that enucleated erythrocytes are advanced than nucleated erythrocytes, but why this advanced feature only limited in mammals? I believe there should be some connection between other features of mammals and their enucleated erythrocytes. Viviparity seems not be the connection, as the evidences shown in the former part of this blog. But I will keep trying to find that. One point I am thinking is that there are two main stages of enucleated erythrocytes development in mammals; the first stage is called primitive erythropoiesis (Palis, 2014), which looks similar with the non-mammal’s erythropoiesis. Investigating their similarities and differences in molecular level, may give us some clue that how enucleated erythrocytes is evolved from nucleated erythrocytes.
Charles A. Long. Evolution of Function and Form in Camelid Erythrocytes. Conference on Cellular & Molecular Biology – Biophysics & Bioengineering, Athens, Greece, August 26-28 (2007) 18–24.
O.K. Baskurta, H.J. Meiselmanb. Lessons from comparative hemorheology studies. Clinical Hemorheology and Microcirculation 45 (2010) 101–108.
Nicholas A. Mauro, Russel E. Isaacks. Examination of Reptilian Erythrocytes as Models of the Progenitor of Mammalian Red Blood Cells. Comp. Biochem. Physiol. Vol. 116A, No. 4, pp (1997) 323–327.
Ahmet A. Baschat, Ulrich Gembruch, Irwin Reiss, Ludwig Gortner, Chris R. Harman, and Carl P. Weiner. Examination of Reptilian Erythrocytes as Models of the Progenitor of Mammalian Red Blood Cells. Am J Obstet Gynecol. Volume 181, Number 1 (1999) 190-195.
Valery M. Gavrilov. Origin and development of homoiothermy: A case study of avian energetics. Am J Obstet Gynecol. Advances in Bioscience and Biotechnology, 2013, 4, 1-17.
James Palis. Primitive and definitive erythropoiesis in mammals. Am J Obstet Gynecol. FrontiersinPhysiology. January (2014) Volume5, Article3. 1-9.