Receptor-mediated uptake and transport of macromolecules in the human placenta

Abstract

The human placenta is required to be the anchor, the conduit and the controller during pregnancy. The survival of the baby and its associated placenta is dependent upon the placenta shielding the embryo/fetus from harm, e.g., autoimmune disease -thrombophilia, antiphospholipid syndrome or infections, while simultaneously providing for the passage of critical nutrients (e.g., amino acids, vitamins) and beneficial immunoglobulins. In a number of instances, the movements of macromolecules into and through the placenta can result in the passage of the intact molecules into the fetal circulation or in the case of proteins -catabolism to amino acids which are utilized by the placenta and the fetus for continued growth and development. The transfer of two such macromolecules, immunoglobulin G (IgG) and vitamin B12 (cyanocobalamin or B12), are examined as to the unique receptor-mediated transfer capability of the human placenta, its transfer specificity as related to specific receptors and the role of endogeneous placental proteins (trancobalamins) in facilitating the recognition and transport of specifically B12. Brief comparisons will be made to other animal species and the differences in specific organ transfer capabilities. KEY WORDS: immunoglobulin IgG, transcobalamin, vitamin B12, placental transport, human Overview of macromolecule transport and catabolism by the placenta and extraembryonic membranes in different speciesThe development of the embryo and fetus is dependent upon the function of the placenta and its extraembryonic membranes in every mammalian species. Of significance is the interdependence of theses extraembryonic tissues in maintaining the conceptus and allowing for normal development.Across species, macromolecules play multiple roles in providing for this development. In particular, the transport physiologists and membrane biochemist focus on the transporters and the transcytosis that occurs for immuno-regulators and essential vitamins for normal development. Yet even the basic building blocks created by the degradation of these macromolecules provide for the growth of both fetus and placenta. The large contribution of amino acids from the metabolism of proteins, e.g., maternal albumin and other circulating proteins, provide the large Int.

Matrix metalloproteinases-2, -3 and tissue inhibitors of metalloproteinases-1, -2 in placentas from preterm pregnancies and their association with one-carbon metabolites

“…The human placenta has a specific receptor for binding transcobalamin (TC II-B 12 ) complex called transcobalamin II-vitamin B 12 receptor (TC II-B 12 R; Schneider & Miller 2010) which is a heavily glycosylated protein (Seetharam & Li 2000). It is known that MMP3 degrades a wide range of substrates including proteoglycans (Hulboy et al 1997).…”

Vitamin B-12 and Perinatal Health

“…Little is known about the pathway of vitamin B-12 transport from the maternal to the fetal circuits, but both vitamin B-12 carrier proteins are produced by the placenta and bind to vitamin B-12 in fetal circulation. Further, the placenta can regulate fetal B-12 uptake by adjusting its rate of TC synthesis (33,34). Impaired TC synthesis can also lead to vitamin B-12 deficiency in the neonate (33).…”

“…Further, the placenta can regulate fetal B-12 uptake by adjusting its rate of TC synthesis (33,34). Impaired TC synthesis can also lead to vitamin B-12 deficiency in the neonate (33).…”

Reduced Folate, Increased Vitamin B₁₂ and Homocysteine Concentrations in Women Delivering Preterm

“…The transcobalamin proteins are produced by the human placenta. In addition, the human placenta has specific receptors for binding transcobalamin [8]. …”