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Biomedical subjects

S Jager

Publications and source records attributed to S Jager.

At least 37 records · Page 2Linked to original sources

Immunological aspects of male infertility.

Some immunological aspects of male infertility are discussed, including the mechanism of induction of auto-antibodies to sperm-specific antigens. Tests to determine antispermatozoal antibodies in serum are discussed. Since there is no direct relation with infertility, more attention is focused on the presence of antispermatozoal antibodies in semen. These antibodies affect male fertility by reducing the capacity of the spermatozoa to penetrate cervical mucus. This penetration inhibition is caused by autoagglutination of the spermatozoa in the ejaculate and by the shaking phenomenon. The sperm-cervical mucus contact test, based on the shaking phenomenon is described. The use of the Mixed Antiglobulin Reaction tests, to detect IgG and IgA antibodies on spermatozoa is discussed. Finally, the effect of antispermatozoal antibodies on the fertilization process is reviewed.

Antigens↗

The tumor marker CA 125 is a common constituent of normal cervical mucus.

The presence of the tumor marker CA 125 was studied in the cervices of healthy women. Immunohistochemical staining of normal cervical tissue demonstrated the presence of CA 125 in the tall columnar cells of the endocervical epithelium but not in the ectocervical squamous epithelium. We measured very high levels of CA 125 in liquefied cervical mucus from women with regular menstrual cycles. At midcycle, levels ranged from 14,200 to 153,000 U/ml (n = 13) in cervical mucus, while normal levels less than 35 U/ml were found in the corresponding serum samples. Levels of CA 125 in cervical mucus are comparable to the high levels found in cyst fluids from ovarian tumors (median 24,600 U/ml, n = 25). When secretion of cervical mucus was stimulated by ethinyl estradiol, equally high levels were found (7900 to 138,000 U/ml, n = 10). We conclude that the tumor marker CA 125 is synthesized and secreted by normal endocervical cells. Apparently an effective barrier exists between the endocervical mucosa and the circulation.

Antigens, Neoplasm↗

Comparison of two supravital stains in examination of human semen and in tests for cytotoxic antibodies to human spermatozoa.

Supravital staining of human spermatozoa using trypan blue was compared with eosin Y staining. The dyes were applied for determination of the percentage of "dead" spermatozoa in semen samples and for determination of complement-dependent antisperm antibody activity in serum. Supravital staining percentages with trypan blue were significantly lower than with eosin Y.

Antibodies↗

Factors related to semen improvement and fertility after varicocele operation.

Factors related to semen improvements and fertility after high ligation of the left internal spermatic vein were investigated in 97 men from infertile couples. Changes in some semen characteristics after operation suggest a relationship between varicocele size and semen improvements and an inverse relationship between preoperative semen values and semen improvements. An inverse relationship seemed to exist between varicocele grades and deterioration of semen values. Fertility after operation was related to age and to semen improvements. Preoperative semen characteristics had no prognostic value for postoperative fertility.

Adult↗

Are sperm immobilizing antibodies in cervical mucus an explanation for a poor postcoital test?

Previous authors reported high incidences of complement dependent sperm immobilizing antibodies in cervical mucus (CM) and found a correlation with poor postcoital tests. In all those investigations the CM samples were tested after dilution with a salt solution. In the present study we investigated 50 CM samples from infertile couples who had during the routine fertility investigation poor postcoital tests. All CM samples were tested after dilution with an equal volume of normal human serum; only one sample was found positive. On the other hand, if the CM samples were diluted with an equal volume of a buffered salt solution, many positive results were obtained. With some guinea pig serum batches, however, all tests with buffer-diluted CM samples were negative, despite good reaction of the positive control serum. We concluded that the positive results with buffer-diluted CM samples were due to a factor in the animal serum used as complement preparation and that complement-dependent sperm immobilizing antibodies in CM are an unlikely cause of a poor postcoital test.

Antibodies↗

Triple staining of human sperm: technical aspects.

The triple-stain technique according to Talbot and Chacon was adapted for use in routine semen analysis. This staining technique allows evaluation of spermatozoal morphology and determination of the percentage of dead and "live" spermatozoa and of the percentages of spermatozoa with and without intact acrosome. Optimal results were obtained if centrifugation prior to fixation was avoided, the semen was diluted before fixation, and the spermatozoa were fixed in suspension. This modification of the triple-stain technique produces preparations with low background and excellent visibility of all spermatozoal structures. Use of Trypan Blue leads to underestimation of the percentage of dead spermatozoa, but use of other supravital stains was even less satisfactory. Round cells could not be evaluated in the triple-stain technique.

Acrosome↗

The effect of oral Kallikrein treatment on sperm motility in asthenozoospermia.

Nineteen men with asthenozoospermia were treated with oral Kallikrein (600 U daily for 12 weeks) and sperm motility evaluated in 16 of these patients. No quantitative or qualitative improvement motility or the duration of motility was found in semen samples examined 4, 12, and 24 weeks after starting the treatment. Two pregnancies occurred 11 and 40 weeks after discontinuation of the Kallikrein therapy.

Adult↗

In vitro swelling of the human sperm nucleus in the presence of sodium dodecyl sulphate.

The in vitro swelling of human sperm nuclei in the presence of sodium dodecyl sulphate (SDS) was studied by counting swollen sperm nuclei in a microscopic preparation and by measuring the decrease of optical density at 600 nm (OD600). At pH 8.0 or lower, OD600 showed a linear relationship to the sperm count. At higher pH values a fraction of the nuclei became swollen and OD600 decreased proportionally, although the sperm count did not change in the first 2 hr. The fraction of swollen sperm nuclei increased with time and by raising the pH or temperature. The swelling occurred only in the presence of SDS and was the consequence of a binding of SDS to the hydrophobic regions of the nuclear proteins.

Cell Nucleus↗

The treatment of ejaculation disorders after retroperitoneal lymph node dissection.

In 14 patients by bilateral retroperitoneal lymph node dissection for nonseminoma tumors of the testes, several sexual functions before and after node dissection were compared. All patients had normal sexual function before the operation. After the operation, antegrade ejaculation was found to have disappeared completely in 12 patients, retrograde ejaculation was demonstrable in ten of these patients. In ten patients, antegrade ejaculation was restored after treatment with 25 mg imipramine twice daily by mouth. In the two patients who still showed antegrade ejaculation, albeit diminished, imipramine medication led to an increased number of spermatoza. During imipramine medication, the partners of five patients became pregnant. The preliminary conclusion from these findings is that ejaculation disorders, which most males develop after bilateral retroperitoneal lymph node dissection, can be successfully treated with daily oral doses of 25-50 mg imipramine in the majority of patients who still desire children.

Adolescent↗

Immunoglobulin class of sperm antibodies in cervical mucus from infertile women.

By immunoaffinity chromatography using anti-IgG, anti-IgM, and anti-IgA coupled to CNBr-activated sepharose 4B, the immunoglobulin class of sperm-agglutinating antibodies was investigated in cervical mucus from four infertile women. In all patients, it was found that the sperm antibodies in cervical mucus belonged to the IgA class, whereas in serum, which was studied in two of the patients, IgG sperm antibodies were demonstrated. Absorption of the four cervical mucus samples with anti-secretory component sepharose 4B revealed that the IgA antibodies in at least two of the samples were SC-IgA antibodies. Investigation of a third sample by sucrose gradient ultracentrifugation revealed that the IgA sperm antibodies were characterized by a sedimentation coefficient between 9S and 13S, strongly suggesting the presence of SC-IgA antibodies. Accordingly, the sperm-agglutinating antibodies were SC-IgA antibodies in at least three of the four samples studied.

Absorption↗

Induction of the shaking phenomenon by pretreatment of spermatozoa with sera containing antispermatozoal antibodies.

Sera containing sperm-agglutinating and/or complement-dependent sperm-immobilizing activity were tested for their ability to induce a shaking phenomenon in the sperm-cervical mucus contact (SCMC) test. Donor spermatozoa were treated with the sera in a one-step incubation and washing procedure. The percentage of motile pretreated spermatozoa showing the shaking phenomenon (S%) was determined in the SCMC test. In addition, the immunoglobulin class of antibodies present on the pretreated spermatozoa was determined in mixed antiglobulin reaction tests for IgG, IgM, and IgA. An S% of at least 80 was always observed with spermatozoa pretreated in sera with a sperm agglutination titer of at least 32, provided that IgG was detected on more than 90% of the motile spermatozoa. The high S% was also obtained with spermatozoa pretreated in purified IgG from sera containing antispermatozoal antibody activity. It was concluded that the reduced cervical mucus penetration capacity of spermatozoa pretreated with sera containing antispermatozoal IgG could be ascribed, at least partially, to the occurrence of a shaking phenomenon.

Antibodies↗

The significance of the Fc part of antispermatozoal antibodies for the shaking phenomenon in the sperm-cervical mucus contact test.

Donor spermatozoa with good motility were pretreated with four sera containing high titers of sperm-agglutinating IgG, one serum without sperm-agglutinating activity, the IgG fractions from these five sera, F(ab)2 and Fragment antigen binding (Fab) fragments from these sera and from the IgG fractions, and one seminal plasma sample with a high titer of sperm-agglutinating IgA. With mixed antiglobulin reaction tests the percentage of motile pretreated spermatozoa sensitized with IgG Fab or IgG Fragment crystalline (Fc) parts was determined. Spermatozoa sensitized with intact antispermatozoal IgG showed a strong reduction in their capacity to penetrate cervical mucus. The reduction of the penetration capacity was determined by estimation of the percentage of motile spermatozoa rapidly shaking (S%) in the sperm-cervical mucus contact (SCMC) test. Removal of the Fc parts resulted in a decreased S%. Treatment of spermatozoa, on which Fab fragments were present, with intact antibodies to IgG Fab fragments, resulted in a recurrence of a high S%. A decrease of the S% was also found if Fab fragments from antibodies to IgG Fc fragments were added to spermatozoa sensitized with intact antispermatozoal IgG. Similarly, it was found that a decrease of the S% occurred when IgA sensitized spermatozoa were treated with Fab fragments from antibodies to human IgA. In the sperm penetration meter test the IgA sensitized spermatozoa treated with Fab fragments from anti-human IgA antibodies showed a better penetration than untreated IgA-sensitized spermatozoa.

Cervix Mucus↗

Immunoglobulin class of antispermatozoal antibodies from infertile men and inhibition of in vitro sperm penetration into cervical mucus.

The presence of IgG and IgA on motile spermatozoa from normal semen donors and men from infertile couples was studied with mixed antiglobulin reaction (MAR) tests. The percentage of motile spermatozoa with IgG (IgG MAR %) was found to be related to the circulating antispermatozoal IgG. No direct relation could be detected between the IgG MAR % and the sperm agglutinating activity in seminal plasma (SP) or the percentage of motile spermatozoa showing the shaking phenomenon (S%) in the sperm cervical mucus contact (SCMC) test. The percentage of motile spermatozoa with IgA (IgA MAR %) showed no direct relation to the sperm agglutinating activity in serum and SP, but was roughly proportional with the S%. It was discerned that the shaking phenomenon in the SCMC test was probably due to presence of IgA on the motile spermatozoa. Previously it had been demonstrated that also the sperm agglutinating activity in SP is caused by IgA that is probably locally produced in the male genital tract. In conclusion it was thought that the reduced ability of penetration into cervical mucus by spermatozoa from infertile men is caused by locally produced IgA.

Cervix Mucus↗

Characteristics of anti-spermatozoal antibodies responsible for the shaking phenomenon with special regard to immunoglobulin class and antigen-reactive sites.

The interaction between spermatozoa and cervical mucus in the presence of antispermatozoal antibodies was studied in the SCMC-test and in the Miller-Kurzrok test. A high correlation was found between: 1. The "shaking phenomenon" in the SCMC-test; 2. sperm penetration into cervical mucus; 3. the sperm agglutination titre in seminal plasma and in cervical mucus. The authors performed investigations which indicate that antispermatozoal IgA in semen and in cervical mucus is probably responsible for the "Shaking phenomenon" in the SCMC-test and for the reduced penetration of spermatozoa into cervical mucus. Experiments with the Miller-Kurzrok test make it probable that antispermatozoal antibodies in semen, which are responsible for the "shaking phenomenon", are directed against the surface antigens of the sperm tails. Antispermatozoal antibodies in cervical mucus, which are responsible for the "shaking phenomenon", are probably directed against the surface antigens of the sperm acrosome.

Acrosome↗

A simple method of screening for antisperm antibodies in the human male. Detection of spermatozoal surface IgG with the direct mixed antiglobulin reaction carried out on untreated fresh human semen.

A simple and rapid test for the detection of antisperm antibodies of the IgG class on freely swimming spermatozoa in fresh human semen is described. The test is based on the formation of motile mixed agglutinates between erythrocytes sensitized with incomplete anti-Rh-antibodies and freely swimming spermatozoa with surface antisperm antibodies, after mixing both cell types together with anti-IgG antiserum. Agglutination of the red blood cells serves as an internal control. The test can be applied on ejaculates with spermatozoa concentrations down to one million per ml, provided the motility is sufficient. The percentage of motile spermatozoa found to be coated with antisperm antibodies of the IgG class, and the extent of the coating, proved to be correlated with the agglutination titer of circulating antisperm antibodies and with the inhibition of sperm penetration into cervical mucus. The test can be used as a screening for the presence of antisperm autoantibodies in serum and semen.

Agglutination↗

Treatment of infertility caused by antisperm antibodies.

Twenty infertile couples with antisperm antibodies in the male or in the female partner were scheduled for treatment. In 15 couples the male and in 5 couples the female partner was the antisperm antibody carrier. In all the couples the result of the in vivo and in vitro sperm-penetration test was negative or poor. The SCMC-test was strongly positive in each of the couples. In all the couples IgG and IgA antisperm antibodies could be demonstrated on the spermatozoa or in the cervical mucus. It was postulated that antisperm IgA and not antisperm IgG is responsible for the penetration reduction of spermatozoa in cervical mucus and for the "shaking phenomenon" in the SCMC-test. Intrauterine inseminations, performed in 20 couples, resulted in four pregnancies. Condom therapy in three couples, for at lest 6 months, had no result. Two men were treated with 96 mg methylprednisolone per day for 7 days; this resulted in a slight decrease of the sperm-agglutination titre, but no pregnancy occurred.

Adult↗