Structure and macromolecular properties of cervical mucus glycoproteins

The endocervical canal is filled with a mucus gel, the properties of which vary during the ovulatory cycle. At mid-cycle the amount of mucus increases, mainly owing to an oestrogen-induced increased hydration of the gel, mucus becomes less visco-elastic and the penetration of the spermatozoa is facilitated. In contrast, under the influence of progesterone during the luteal phase, mucus turns into a less hydrated, highly visco-elastic structure which acts as a barrier to sperm. The mucus gel is formed by very large and structurally complex glycoproteins perfected by evolution to tease and disunite the scientists engaged in unravelling their secrets. The macromolecules are referred to as the mucus glycoproteins or the mucins. Hydrodynamic studies show that cervical mucus glycoproteins (Mr 10-15 x 10(6] behave as random coils, which occupy large spheroidal domains in dilute solution. The predicted 'linear' structure is supported by evidence obtained with electron microscopy. By this technique, the macromolecules are visualized as 'threads' with a skewed and polydisperse distribution of contour lengths (number-average length, 1.5 microns; range 0.5-5 microns). The macromolecules may be cleaved into subunits (Mr 2-3 x 10(6] by reduction of disulphine bonds and these fragments can be divided into large glycopeptides (T-domains; Mr 300,000-400,000) by trypsin. Most of the carbohydrate, which accounts for approximately 80% by weight of the macromolecule and occurs as a heterogeneous population of oligosaccharides, is enriched within the T-domains. The high-Mr glycopeptides thus correspond to long (of the order 100 nm) stretches of protein covered with 100-300 oligosaccharides which protect the core from proteolysis. These regions of the macromolecule are referred to as oligosaccharide 'clusters' and subunits of cervical mucins contain, on average, 3-5 of these 'clusters'. Each 'cluster' is flanked by stretches of protein which are less substituted with carbohydrate and, consequently, more sensitive to proteolysis. There is evidence that these parts of the core, referred to as the 'naked' regins, are folded and stabilized by disulphide bonds. Cervical mucus glycoproteins may thus be viewed as a linear array of oligosaccharide-rich 'clusters' alternating with structures reminiscent of a globular protein. Little is known about how the mucus glycoproteins interact to form the gel. The classical 'Odeblad concept' postulates that the mucins form bundles ('micelles') which are then interconnected in a hormone-dependent way. In contrast, light-scattering studies suggest that cervical mucus is an entangled net-work of long and flexible macromolecules.(ABSTRACT TRUNCATED AT 400 WORDS)