Placental Sequestration of Heavy Metals he heavy metal-binding protein metallothionein-1 is expressed in human syncytiotrophoblast. his protein binds and sequesters a host of heavy metals, including zinc, copper, lead, and cadmium. Despite this, fetal exposure is variable (Caserta, 2013). For example, lead enters the fetal environment at a level 90 percent of maternal concentrations. In contrast, placental transfer of cadmium is limited (Kopp, 2012). he most common source of environmental cadmium is cigarette smoke.
Metallothionein also binds and sequesters copper (Cu2+) in placental tissue. This accounts for the low levels of Cu2+ in cord blood (Iyengar, 2001). It is possible that cadmium provokes metallothionein synthesis in the amnion. his may cause Cu2+ sequestration, a pseudo-copper deficiency, and in turn, diminished tensile strength of the amnion.
he concentration of vitamin A (retinol) is greater in fetal than in maternal plasma and is bound to retinol-binding protein and to prealbumin. Retinol-binding protein is transferred from the maternal compartment across the syncytiotrophoblast. The transport of vitamin C-ascorbic acid-from mother to fetus is accomplished by an energy-dependent, carrier-mediated process. Levels of principal vitamin D metabolites, including 1,25-dihydroxycholecalciferol, are greater in maternal plasma than in fetal plasma. The 1 3-hydroxylation of 25-hydroxyvitamin D3 is known to take place in placenta and in decidua.
The placenta is the organ of transfer between mother and fetus.
Within this maternal-fetal interface, oxygen and nutrients transfer from the mother to the fetus, whereas CO2 and meta bolic wastes are directed from fetus to mother. Fetal blood, which is contained in the fetal capillaries of the chorionic villi, has no direct contact with maternal blood, which remains in the intervillous space. Instead, bidirectional transfer depends on processes that allow or aid the transport through the syncy tiotrophoblast that lines chorionic villi.
Over the past few years, it has become apparent that breaks in the chorionic villi permit escape of fetal cells and other bloodborne material into the maternal circulation. This leakage is the mechanism by which some D-negative women become sensitized by the erythrocytes of their D-positive fetus (Chap. 15, p. 301). In fact, after 10 weeks, 10 to 15 percent of cell-free DNA (cDNA) in maternal plasma is placental in origin, that is, trophoblastic DNA (Norton, 2012). he escape of fetal cells can also lead to fetal microchimerism from entrance of allogeneic fetal cells, including trophoblast, into maternal blood and other organs (Rijnik, 2015). Volumes are estimated to range from 1 to 6 cells/ mL at midpregnancy. Some fetal cells become "immortal" in that they persist in the maternal circulation and organs following pregnancy. As discussed in Chapter 59 (p. 1139), the clinical corollary is that some maternal autoimmune diseases may be provoked by such microchimerism.
• The Intervillous Space vIaternal blood within the intervillous space is the primary source of maternal-fetal transfer. Blood from the maternal spiral arteries directly bathes the trophoblast layer that surrounds the villi. Substances transferred from mother to fetus irst enter the intervillous space and are then transported to the syncytiotrophoblast. As such, the chorionic villi and intervillous space function together as the fetal lung, gastrointestinal tract, and kidney.