Hyperglycosylated hCG: a Unique Human Implantation and Invasion Factor

Human chorionic gonadotropin (hCG), as one of the first embryonic products, has been extensively investigated for its role in implantation and placental development. Discovery of an over-glycosylated form of this hormone, hyperglycosylated hCG (hCG-H), has provided an additional level of complexity in our understanding of the implantation and placentation process; the structure, activity and functional implications of alterations in hCG isoforms throughout pregnancy are still being characterized. HCG-H comprises up to 90% of total hCG measurable in serum and urine during the first 2-3 weeks of pregnancy when invasive trophoblast activity is high, dropping to negligible proportions, less than 5%, of total hCG at the end of the first trimester. Functionally, hCG-H promotes trophoblast invasion during early pregnancy and has potential roles in immune cell modulation and endothelial function within the uterus at the time of pregnancy initiation. Altered levels of hCG-H are characteristics of pregnancy complications of altered trophoblast function and inadequate placentation, such as pre-eclampsia, and also over-abundance of invasive cytotrophoblasts, such as Down's syndrome. Improving our basic knowledge of the functional role-specific hCG isoforms plays in the complex cascade of events involved in implantation and placental development, and determining dynamic changes in the structure and activity of hCG isoforms throughout gestation will facilitate evidence-based decisions in assisted reproduction/in vitro fertilization based on the potential of embryos to implant, provide biomarkers for diagnosis of pregnancy complications associated with altered placental development and enhance understanding of how hCG isoforms may influence receptivity of the endometrium.