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  • Title: Changes in cervical mucus that prevent penetration by spermatozoa.
    Author: Chantler E, Sharma R, Sharman D.
    Journal: Symp Soc Exp Biol; 1989; 43():325-36. PubMed ID: 2701482.
    Abstract:
    Two situations that result in the conversion of human mid-cycle cervical mucus from a sperm-receptive to a sperm-hostile form are described here: firstly, the addition of mucospissic agents, and secondly, the presence of antisperm antibodies. Two mucospissic biguanides were studied, chlorhexidine and Vantocil; both were totally spermicidal in the range 1-10 mg ml-1. Treatment of mucus with 1.5 microM to 1.65 mM Vantocil caused a dose-dependent increase in the dynamic storage modulus. The compatibility of the two biguanides with mucus was examined by measuring the rate of entry of diffusion of the [14C]biguanides into mucus. Chlorhexidine entered the mucus up to 0.53 mM, i.e. the highest concentration used, whilst Vantocil only entered at concentrations below 0.53 mM. This limited entry may be caused by the precipitation of mucus at the interface, producing a barrier of reduced permeability. The behaviour of purified mucin on ultracentrifugation was also altered after treatment with chlorhexidine. The s20 (at 2 mg ml-1 purified mucin) increased from 11.2 S to 19.3 S upon addition of 200 microM chlorhexidine. Further indication of structural alteration of biguanide-treated mucin was given by its loss of solubility in 0.22 M-sodium thiocyanate. The application of these biguanides to vaginal contraception is suggested. When antisperm antibodies are present in either the semen or cervical mucus, we suggest that an interaction can occur between galactose residues on the spermatozoa and galactose recognition sites on the antisperm antibody; in addition, binding can also occur between the Fc region of the antibody and cervical mucus. This process could therefore contribute to the binding of spermatozoa to the antibody and the immobilisation of this complex by the cervical mucus that is seen in immunological infertility. It was shown, by Immunobead binding, that immediate exposure of spermatozoa to D-galactose in the presence of chymotrypsin resulted in a considerable decrease or total loss of bound antisperm antibodies in males who had previously had a high titre of antibody. This reduction in the antibody level on the spermatozoa was accompanied by the appearance of the antibody level on the spermatozoa was accompanied by the appearance of the ability of the spermatozoa to penetrate cervical mucus in those couples examined. This pretreatment regimen for the ejaculate is suggested as a form of therapy for infertility related to the presence of antisperm antibodies. After a brief review of the molecular structure of cervical mucus, the data are presented on inhibition of sperm transport through cervical mucus by polyanions and on enhancement of sperm penetration in cases of infertility due to antisperm antibodies. Cervical mucus is a gel made up of large, unbranched, glycosylated glycoprotein with highly glycosylated domains separated by hydrophobic peptide chains. Spermatozoa probably traverse the unbound water phase rather than the water bound to the macromolecules. Since mucin is a polyanion, polycations were investigated as potential vaginal spermicides. The two biguanides studies, chlorhexidine and Vantocil were both spermicidal in concentrations of 1-10 mg/ml. Their rate of entry into mucin in capillary tubes differed. Vantocil penetrated superficially and set up a barrier of inspissated mucus. Chlorhexidine entered further, with dept inversely proportional to concentration. Both biguanides increased the thickness of cervical mucus in a dose-dependent manner, as judged by dynamic storage modules, by sedimentation in analytical ultracentrifugation, and by solubility in 0.22 M thiocyanate. It was speculated that these biguanides act by altering the molecular configuration of mucin. In the presence of anti-sperm antibodies, spermatozoa observed in cervical mucus in vitro may show non-progressive mobility or immobility. The presence of auto-antibodies can be shown with Immunobeads. Binding of secretory IgA to sperm can be cleaved with bacterial protease as can binding of IgG with trypsin. By assaying the blockage of sperm by antibodies with Immunobeads and measuring penetration of sperm in donor cervical mucus, displacement of sperm antibodies could be demonstrated in 9 infertile subjects. Therefore, it might be possible to treat the ejaculate with proteases, and achieve conception by either a gamete intrafallopian tube transfer or an in vitro fertilization procedure.
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