The Biology of the Cervix

A Summary of Recent Advances from the Work of Erik Odeblad

in collaboration with

Erik Odeblad, Professor Emeritus, Dept. of Medical Biophysics, University of Umeå, Sweden

Ó Ovulation Method Research and Reference Centre of Australia

Professor Odeblad began investigating the biophysical properties of cervical mucus secretions by nuclear magnetic resonance (NMR) when this became available in 1957 (18). He found that there were two different types of hydrogels, a less viscous replacing a more viscous one as ovulation approached (8, 16).

Microscopic observations on wet mucus under the microscope (5,6) supported NMR and it was proposed that the cervical mucus is a mixture of "rods" of different composition, probably emanating fromn different crypts (clefts) in the wall of the cervical canal. Later (7) this was supported by direct observations of mucus aspirated from different crypts by means of micro-NMR.

The endocervix has a rather complicated anatomy (1, 21), with exophytic structures (folds and "grapes") and endophytic structures (clefts, crypts, "tunnels"). Secretory unit (SU) would perhaps be a better expression than crypt because an assembly of secretory cells producing a certain type of mucus is confined to an anatomical crypt in only about 70 per cent of cases (13). However, the word crypt is now in widespread use.

G, L, S and P, the Main Types of Cervical Mucus

Two distinctly different types of single-crypt mucus were characterised (1968), (8), G, from crypts reacting to gestagenic stimulation , and E, from crypts reacting to oestrogenic stimulation. The E-type was later (2, 9, 10) divided into L-type and S-type mucus, L for "loaf'-shaped rods and S for sting-shaped. S also stands for "sperm-conveying" mucus.

Further microscopic studies (13) showed that the G mucus always contained varying numbers of cells, usually more abundant after ovulation (G+) than before it (G-). Furthermore it was found that the L mucus was responsible for the typical rectangular "ferning" crystallising pattern (21, 22). S mucus showed many more tiny crystals, often long, thin, needle-like structures. Some of these tiny crystals, however, showed a branching of crystals usually about 60 degrees as against the 90 degree branching of L mucus crystals. This type of crystal showed a cyclic variation different from both L and S mucus crystals. It most often had a maximum appearance on days of peak fertility and was therefore named P mucus (13). It too was present in various subtypes with different crystal symmetry, often twofold (hence P2) or sixfold (P6) (13). These distinctions became possible by gently smearing cervical mucus thinly on a slide in all directions, thus separating the different types from each other. This "spread out technique" was used for many years before being published in 1994 (14).

The "spread out technique" enabled the identification of several previously undefined structures in cervical mucus. Small granules (13, 14, 15, 16) about 1m m in diameter have been defined, probably secreted by glands in the isthmus, between the upper cervical canal and the body of the uterus. These granules probably contain several enzymes, one of them having a mucolytic (mucus-dissolving) action. The granules have an affinity for P2 mucus and, to a smaller degree also for other mucus types, which become slowly degraded by their action. Because of this high affinity to P2 mucus this mucus was also denominated Pa ("a" for action or activity).

Another observation in these well-spread-out specimens is the presence of assemblies of non-ciliated epithelial cells without the presence of leucocytes or lymphocytes (14, 16). These assemblies are more common in early menarcheal and post-menopausal samples than in women of fertile age. Probably they do not have a direct fertility-promoting function. They may be cells of more fundamental importance, such as the stem cells from which G, L, S and P secretary cells develop. They have therefore been named F cells.

Another important advance was that these extremely thin samples allowed the observation of single cervical cells which are normally expelled in the mucus (16, 21). The first cells which received attention occurred in areas of P mucus ad wee surrounded by a secretion with triangular crystal formations, and were therefore called Pt cells. Recent studies indicate that the Pt secretion is identical with the P6 secretion and that several subtypes of Pt secretion depend on altered secretion coming from normally apoptotic or prenecrotic P cells.

The cells giving rise to P2 (=Pa) mucus have another appearance in the spread-out samples. Also they seem to have different cyclic appearance. P2 cells dominate in the beginning of the fertile period, P6 at the end of the fertile period (16).

It has been suspected for a long time that P mucus might have something to do with immunological processes in the cervix, because cell constellations resembling contacts between macrophages and lymphocytes have been observed (19) when P secreting mucus cells are present. Initially it was thought that there was a correlation between Pt cells and such immuno-processes, but after we leaned to identify P2 cells, a stronger correlation with the P2 cells was indicated.

In the development of the field of P cells and P mucus a collaboration with Spanish researchers has been very important, especially with Mikaela Menarguez in Murcia (3, 4) and Helvia Temprano in La Coruna (23). They have performed scanning electron microscopy, transmission electron microscopy and X-ray microanalysis on cells and crystals which has helped to clarify many of the problems involved in this research.