The hCG, hyperglycosylated hCG and hCG free ß-subunit story does not stop at pregnancy, hydatidiform mole, GTN and choriocarcinoma, it stretches on to cancer. This is because these are such potent growth and invasion promoters. They were developed this way to drive evolution, to permit the development of the human brain. The importance of hCG to human evolution, and how humans came about is described here.
Most mammals use an inefficient form of fetal placentation called epitheliochorial placentation (see Table). Nutrients had to pass through multiple layers of maternal uterus to enter the multiple layers of placenta, not very efficinent. As a results, most mammals had a small brain, because of lack of fetal nutrient supplies, approximately 0.10% of body weight (see Table).
Table. Parallelisms between placental implantation, invasion characteristics, sugar structure on hCG or LH, and relative brain masses.
|Species||Implantationcharacteristics||Depth ofimplantation||Sugar structures of CG/LH||Brain mass% body weight||First AppearedYears ago|
|Humans||Hemochorial||40% uterus||CG 8 oligosaccharides||2.4%||0.1 million|
|Advanced.simian_||Hemochorial||10% uterus||CG 6 oligosaccharides||0.74%||20 million|
|Early simian||Hemochorial||only decidua||CG 5 oligosaccharides||0.17%||37 million|
|Prosimian.primate||Epitheliochorial-||No implantation||LH 3 oligosaccharides||0.07%||55 million|
|Horse||Epitheliochorial||No implantation||LH 3 oligosaccharides||0.10%||50 million|
|Elephant||Epitheliochorial||No implantation||LH 3 oligosaccharides||0.13%||60 million|
The earliest primates, prosimian primates (e.g. Lemur) used epitheliochorial placentation like other mammals, and had a small brain, just 0.07% of body weight. In the early simian primates (e.g. Marmoset monkey), the next level of evolution, evolved CG (not human so CG instead of hCG) as a genetic variant of luteinizing hormone (LH), with a genetically longer ß-subunit (145 vs. 121 amino acids). This gonadotropin was produced by the placenta. CG and its variant hyperglycosylated CG promoted placental growth and invasion, or implantation leading to hemochorial placentation. In hemochorial placentation just one cell separates the fetal and maternal circulation, the syncytiotrophoblast cell of villous placenta tissue. The first CG had 5 oligosaccharides or sugar side chains (see Table), so was not very acidic and not long circulating in the blood (blood ½-life ~2 hours) or very potent. As illustrated in the Table, this weak first form of CG promoted invasion of only the inside skin or decidua of uterus, it promoted the formation of villous placenta tissue, and not very efficient placental growth or hemochorial placentation. The end result is that these primates only developed a brain of 0.17% of body mass.
Then evolved advanced simian primates (e.g. orangutan and baboon), these evolved a CG with 6 oligosaccharides making it more acidic. This molecule now had a blood ½-life of ~6 hours. This more potent molecule was able to promote invasion to 10% of the uterine thickness and much greater placental growth and villous placental tissue formation. This led to more efficient hemochorial placentation. These primates developed a fetus with 0.74% brain mass. Then evolved humans with a much more acidic CG and hyperglycosylated CG with 8 oligosaccharides side chains, This molecule was much more acidic and had a blood circulating ½-life of 37 hours. This extreme potent molecule was able to take implantation to its extreme at 40% uterine thickness and promote extreme placental villous growth. This led to extremely efficient hemochorial placentation, such that it could support a fetus with 2.4% brain mass. Studies show that in humans 60% of glucose and oxygen transferred by placenta is used to support brain development.
Evolution scientist have questioned for years how did humans get around the mammal and primate placentation limitation and develop a large brain. The answer is CG and hyperglycosylated CG and their evolving acidity and efficiency at promoting placental growth and placental implantation.