The Discovery of Different Types of Cervical Mucus - Erik Odeblad

  Identification and Description of G, L and S Mucus

At the end of 1968 1 had identified and characterized two types of mucus, one with a high viscosity (G) the other with a low viscosity (E). E mucus was stimulated by oestrogens and G mucus by progesterone, G mucus being produced in G crypts, E mucus in E crypts. Also we isolated the liquid phase (aqueous, in the lattice structure) of mucus. This phase was named secretion B since it resembled blood serum (Odeblad and Rosenberg 1968). The B component is temporarily secreted in excess during an hour after mechanical stimulation of the cervix. Like the P mucus (as will be discussed below) it may carry enzymes from the isthmus region downwards in the cervical canal. The B secretion will be discussed in more detail in a forthcoming paper.

Research during the years 1970 to 1975 indicated that the progression of spermatozoa in E mucus was complicated and it was evident that E mucus was composed of two different types of mucus, named S (-sperm-transmission) mucus and L (- locking-in) mucus because of the capacity of that mucus to attract and enclose malformed sperm (Figure 5). These results were published (Odeblad 1977, 1978; Hglund and Odeblad 1977) and the G - L - S model was able to explain the major factors associated with the upward movement of sperm in the cervical canal.

The discovery of G, L and S mucus was presented for the first time at the University of Surrey, England, in 1976, and later at Rottach-Egern, Stockholm, New Delhi, Seattle, and in Sydney, Australia, in 1977. Most of the audiences did not understand how to apply this new knowledge. Dr Max Elstein of England readily accepted the G - L - S model but Dr Kevin Hume of Sydney, Australia, appreciated the significance of the discovery. Dr Hume was a member of the Billings group and he drew my attention to the fact that G mucus would be present in the infertile phase of the woman's menstrual cycle, and L and S types during the fertile phase, and also that S mucus would correspond with the Peak day. This was the beginning of my participation, collaboration and commitment to the Billings Ovulation Method. Following Dr Hume's recommendations, I showed for cycles of different lengths, and in women of different ages, that the agreement was statistically significant. This finding was presented at a number of conferences in several countries, towns and universities, for example in Acapulco in 1982 (published in 1983), in Melbourne in 1983 and in Paris in 1986 (Odeblad 1987).

Figure 5. Viscosities of micro-samples of different types of mucus.

Studies (Odeblad et al. 1984) showed that S mucus was very fluid (Figure 5) and that sperm cells moved along the canal very rapidly in S mucus, reaching the S crypts in 3-10 minutes. L mucus had a medium viscosity. Unit structures of L mucus attracted malformed sperm cells or those which moved slowly, and this "filtration" of sperm cells is efficacious (Odeblad 1985). G mucus has a high viscosity and forms a sort of impenetrable plug (Odeblad et al. 1983).

If we take a macrosample of cervical mucus and allow it to spread out on a glass slide we are able to see with the aid of a microscope some interesting patterns (Figure 6). L mucus shows very fine crystals in the shape of rectangular leaves. In S mucus one sees crystals of another configuration -- small, thin needles. G mucus does not exhibit any crystals, but epithelial cells, leucocytes and lymphocytes. The nuclei of these cells are very abundant (Figure 7). NMR studies indicate that the water of S mucus is associated with the mucus in such a way as to form a structure which facilitates the forward movement of sperm cells (Figure 8; Odeblad 1966a).

(a)

(b)

Figure 6. All mucus types present in one cervical sample obtained from a virgin woman 18 years old. Figure 6(a) shows types L (x 30), S (x 80), G- (x 80) and G+ (x 160). Note that the magnifications are all different for the different types. Figure 6(b) shows the secretions P6 (x 80), Pa (x 80), F (x 480), and Z (x 320). The F secretion contains a few leucocytes (rounded cells) among the epithelial cells (elongated) because some G secretion overlaps the F mucus. In the picture of the Z secretion one can see (to the bottom) the enzyme grains tend to aggregate into ring formed structures. To the top grains are absorbed on Pa mucus. Note that the magnifications are different for the various photos. The sample was taken the day after ovulation, approximately 17 hours after the ovulation had taken place. The woman was healthy and the large amount of leucocytes and lymphocytes in the G+ sample is a normal phenomenon.

Figure 7. Comparison of G+ mucus with F mucus. G+ mucus has more leucocytes and lymphocytes. None of these cells are found in F mucus, only epithelial cells. (x 600)

In 1983 1 had the privilege of working with Drs John and Evelyn Billings in Melbourne and also with Professor James Brown and other research workers of the Ovulation Method. The hormonal response of G, L, and S mucus was studied. We found that L mucus was stimulated by medium and increasing levels, and S mucus by high levels, of oestrogen. Later I showed that S mucus was also stimulated by noradrenaline. G mucus was stimulated by progesterone. In the first infertile phase of the cycle the progesterone level is low, but sufficient to stimulate G crypts feebly (G-mucus). After ovulation, progesterone levels are high and stimulate G crypts strongly. This G mucus is very dense (G+ mucus).

Figure 8. Enlarged NMR spectra of S, L and G+ mucus compared with that of water. This investigation demonstrated hydrogen-bonding in the aqueous phases (A) of S, L, and G+ mucus. Waves H and M are reference signals which enable the position of the aqueous signals to be obtained with very high precision. The wave shifts indicate that the water of S mucus has a small resistance to sperm cells but that of G+ mucus presents a much greater resistance.

Usually no sensation is associated with G mucus, and the days are dry during the infertile phases. When oestrogen levels increase L mucus begins to be produced, and wetness is felt, firstly with a sticky sensation. Later, when oestrogen levels are high, and S mucus is also produced, there is a slippery or lubricative sensation (Figure 15), and this sensation remains until the Peak day. On that day oestrogen levels are already decreasing but the noradrenaline-like activity of the sympathetic nervous system causes stimulation of the S mucus. Figure 15 shows the temporal relations of the different secretions. After the Peak day G mucus is accompanied by a return to a dry sensation due to the abundant secretion of progesterone by the corpus luteum.

 

  G- and G+ Mucus

The two variants of G mucus are produced by: the same crypts, depending upon the levels of progesterone in the blood. My studies in Melbourne showed a positive correlation between the amount of progesterone and mucin content and also the number of cells in the mucus. G mucus, especially G+ mucus, probably contains antimicrobial globulins, probably the substance which occasioned the inactivation of mycoplasms in my microbiological investigations, whilst the mycoplasms were able to survive in L and S crypts which were inactive in the post-ovulatory phase.

It is important to recognize that the cells of G mucus are of three types: (i) epithelial cells; (ii) leucocytes; (iii) lymphocytes. Their proportions are variable, usually about 50% epithelial cells, 25% leucocytes and 25% Iymphocytes, but larger variations are possible, depending upon different factors. Certain women always have many lymphocytes, others have many leucocytes. Interleukins may play a role for the presence of lymphocytes and leucocytes (Cannon and Dinarello 1985). Local or general. inflammations are able to influence the proportions.

The viscosities of G- and of G+ mucus are given in Figure 5 and Table 2. The two types are impermeable to sperm cells. In non-ovulatory cycles the G+ mucus is not produced. During pregnancy, G+ is more viscous and is called Gp mucus (p - pregnancy).

 

  Age, Pregnancy, the Pill and Microsurgery

In young women around puberty S crypts are very numerous. Normally they are replaced by L crypts, and at premenopause the number of S crypts is considerably reduced. This transformation of L ® S crypts is a normal process. There is also a G ® L transformation. Also some columnar secretory cells on the portio are replaced by stratified epithelium which advances in a centripetal manner towards the cervical orifice. The L ® S and G ® L transformations are partially reversed by changes during pregnancy, but they are partially accelerated by the Pill. These circumstances may be simply stated by the expression: a pregnancy rejuvenates the cervix by 2-3 years, but for each year the Pill is taken, the cervix ages by an extra year.

If a woman takes the Pill for 10-15 years and then ceases taking it in order to achieve pregnancy, she may encounter some difficulties. Studies indicate that the number of S crypts are very few and, as well, the cervical canal will be very narrow. In such cases I have attempted to imitate, by microsurgery, the rejuvenation which normally occurs during pregnancy, that is to allow S cells to "take over" the L crypts. Sometimes, in about 40% of cases, this microsurgery was not successful.