G mucus is present in the cervical canal in all phases of the menstrual cycle except during the fertile phase and menstruation. It acts as a natural barrier to sperm, while the presence of leucocytes, lymphocytes and gammaglobulins suggest that the G mucus is a protective substance. Its high viscosity and glue-like character make it also a mechanical plug, closing the cervical canal, which is also narrowed during the infertile phases by the fibromuscular action of the cervix.

The L mucus has an intermediate viscosity and is secreted during the whole of the fertile phase. During the process of secretion the L crypt gradually fills with L mucus, then being expelled as a "pearl" or "loaf' of transparent mucus, probably 30 or more such units are produced during the fertile phase in each L crypt, forming rows of "pearls". These arrays of L mucus form a flexible mechanical support for the S mucus, and is a dynamic "mosaic" (11). The S mucus appears from 1 to 3 days later than the L mucus. Another function of the L mucus is to capture sperm which deviate from the S mucus during sperm ascent. Having entered the L mucus the sperm have difficulty escaping, the L mucus in this way acting as a filter for imperfect sperm. Certain areas of the "loaves" known as micropockets seem more apt to perform this function. Recent research indicates, however, that also the glycoprotein structure itself (17) in the L mucus may play a part in selecting away "undesired" sperm cells in the advancing population of spermatozoa.

The S mucus, which contains long molecular filaments, is usually secreted in crypts adjacent to the L crypts. Usually there is a contact between the upper end of a filament of the S mucus and the L mucus while the lower end of the filament is free-floating (12). The filaments, also called micelles, are made up of glycoproteins and/or proteoglycans and are about 0.5m m thick, their lengths being approximately logarithmically normal, distributed around a mean of about 0.5mm (17) at the time of peak fertility. Normally the filaments may be a little branched at their lower portions. Excessive branching seems to reduce fertility. Rapidly swimming sperm appear to propagate between the filaments and may reach a crypt within 4 to 15 minutes. There may be a downward flow of about 15m m/sec within a string of S mucus. This flow is essential because it gives an upward orientation of the swimming sperm. So the cooperation of the L and S mucus establishes optimal sperm propagation to a crypt.

With better understanding of the mucus sub-types it became obvious that P2 could be present as early as at the beginning of the fertile phase 4-8 days before ovulation. It was also found that P2 often showed absorption of granules and mucolytic activity. Not only did it decay but it also induced mucolysis in other types of adjacent mucus. Its physiological role may be to liquefy the G mucus to give space for the L mucus, and the. to liquefy the L mucus to facilitate the S mucus flow which is necessary for sperm propagation to the crypts. After the sperm have resided in the S crypts, mucolysis may help to liquefy the L mucus, now blocking the crypt outlets, so that sperm can continue upwards.

P6 mucus is mostly confined to the uppermost part of the cervix, probably conveying sperm in the chinks between "plates" of mucus. Each such plate appears as a crystalline hexagonal star in the thinly spread dried mucus specimens. P6 is mainly present at and shortly after ovulation.

P2 and P6 are the most common varieties of P mucus.

Sperm Migration in the Cervix

Sperm invade the S mucus strings at the external mouth of the cervix and propagate along them, the majority being conveyed to the S crypts, although a few may find their way directly to the uterine cavity. In the S crypts they seem to reduce or lose their movements. Here they may "hibernate" for a few hours up to some days, the average time being about 16 hours. When the sperm enter the crypt the S mucus secretion rate seems to diminish or disappear. Some women attempting to achieve pregnancy have even noted a temporary decrease of the slippery sensation during the day after intercourse. The mechanisms governing sperm immobilisation and inhibition of secretion are not known. Some kind of neural factor can be expected. After a day or so sperm are released from the crypts and begin to propagate, finding their way to the uterine cavity between the disc shaped units of P6 mucus.

These have been described for the G-L-S- model (22) and for G-L-S-P2-P6-F- model (16). This last model is, in brief, for an average normal cycle as follows:

After menstruation mucus G- dominates and gives rise to the Basic Infertile Pattern (BIP). After some 4-6 days it becomes successively replaced by the L mucus, and the fertile phase begins with the sensation of a wet, tacky mucus. Some days later the S mucus appears with a transition to wet, slippery mucus culminating on the Peak day with an extremely wet, lubricative vulva sensation (S mucus about 25 %). This sensation then usually disappears quickly and within 1-2 days the G mucus dominates the mucus and remains during the whole second infertile period. Mucus types P2, P6 and F usually are all under 5%. P2 has its highest value in the beginning and P6 in the end of the fertile period. F mucus shows small variations within 1-3 %. Together with the mucolytic enzyme the P2 mucus gives way for the L mucus and later the S mucus, and P6 + mucolytic enzyme facilitates sperm migration at the end of the fertile phase and also brings about the Peak sensation.

This is an important principle (16) which seems to regulate, in general, the behaviour of all mucus types of the cervix. BRAMS is an acronym for the following:

B = biosynthesis of mucus within the epithelial cells.

R = release of mucus from the cell. Oestrogens seem to stimulate biosynthesis and noradrenalin release of S mucus.

A = activity or activation (e.g. biological activity such as sperm conduction or polymerisation of mucin molecules to mucus substance).

M = mucolysis (degradation, depolymerisation) partial or complete, with or without the cooperation of a mucolytic enzyme.

S = sensation of mucus and/or its degradation products, as perceived usually at the vulva.

The BRAMS principle stresses the importance of a balance between mucus production and degradation, a kind of homeostasis. When the BRAMS principle is applied to normal L mucus: it is biosynthesised in the L crypt, it polymerises and is released, forming the "loaves" or "pearls" which help to detach low-quality sperm from the main stream of swimming sperm in the S mucus. It begins to depolymerise when passing through the vagina, giving the typical wet, sticky sensation at the vulva.

Investigations at the Cellular Level

It has already been mentioned that the elementary P6 mucus, the Pt secretion, can most easily be identified in very thin specimens of spread out, dried (not fixed or stained) mucus. It requires high magnification to be clearly observed. It presents a remarkable pattern and seems to permit interesting possibilities for studies in the secretion mechanisms. A specialised cotton wool swab technique has been devised for removing Pt mucus and secreting epithelial cells without damaging them (21). Thus cells, apparently in different secretory phases, can be obtained for study with electron microscopy. It has already been possible to identify (probably) various stages of P6 secretion.

Another area of cellular studies is the apparently immunological (19) events which may occur in the cervix and cervical secretion which may be associated with the lymph node sign, a symptom which can help to indicate the optimum time for conception in some cases of infertility.

There exists a problem which has been subjected to much discussion and diverging opinions, the case for sex selection and recommending the time for coitus in relation to the Peak day. It has been suggested that the different weight or size of X and Y sperms might result in sex selection, but it could also be that different carbohydrate composition and arrangement in sperm surface glycoproteins may play a role by adhering differently to successively changing S+P mucus structure around ovulation. Future investigations may shed some light on these questions (17).

A very important field is also the cellular response to different steroid stimulation, both normal and synthetic steroids, their levels and time distributions, their influence on the various members of the steroid receptor family and the hsp-90 inactivate proteins and other factors involved in transcription, biosynthesis, cell growth and cell degeneration (apoptosis and necrosis). Such studies are intimately connected with the use of steroid contraceptives, given orally, by injection or via other routes.