Changes in the Composition and Structure of Glycosaminoglycans in the Human Placenta during Development

摘要

Extract: Glycosaminoglycans (acid mucopolysaccharides) are ubiquitous in their distribution in the body, yet information as to their biologic function is scanty. Studies of their structure and physical properties in solution suggest that they could function as gel nitration and exchange resins in vivo, thereby playing an important role in regulation of the passage of molecules through the ground substance of connective tissue. The glycosaminoglycan(s) (GAG) composition of the human placenta and the molecular structure of specific GAG has been studied by chemical, enzymatic, and physical methods at 12–18 weeks and at 40 weeks gestational age to explore this postulated structure-function relation.The young placenta contained more GAG (222 mg/100 mg dry defatted tissue) than did the term placenta (155 mg/100 g dry defatted tissue). Sulfated GAG comprised 56% of the total GAG in the young placenta versus 74% in the term placenta due to increased concentrations of dermatan sulfate (25% term versus 13% young placenta) and heparan sulfate (22% term versus 15% young placenta). Ghondroitin was a major component in the young placenta and comprised 22% of the total GAG, whereas the term placenta contained only 9%. Both young and term placenta showed similar quantities of hyaluronic acid and chondroitin 4? and 6-sulfates. Ghondroitin sulfate from the young placenta differed from the polymer in the term placenta in that it contained a higher proportion of unsulfated dissaccharides. Differences were also found in the molecular structure of dermatan sulfate. Hyaluronidase digestion of purified dermatan sulfate from young placenta produced a 50% reduction in average molecular weight compared with a 30% reduction in the molecular weight of dermatan sulfate isolated from term placenta. The smaller molecular weight fragments of dermatan sulfate from young placenta indicate differences in molecular structure due either to the number of glucuronic acid substitutions or to their position in the polymer chain, or to changes in the concentration of hybrid molecules.Speculation: The age-related changes in the composition and molecular structure of placental glycosaminoglycans will result in ground substance gels of differing physical properties. This could alter the transport of molecules through placental connective tissue and affect the rate of fetal growth.