Antibody-Mediated Immobilization of Virions in Mucus.

Antibodies have been shown to hinder the movement of herpes simplex virus virions in cervicovaginal mucus, as well as other viruses in other mucus secretions. However, it has not been possible to directly observe the mechanisms underlying this phenomenon, so the nature of virion-antibody-mucin interactions remain poorly understood. In this work, we analyzed thousands of virion traces from single particle tracking experiments to explicate how antibodies must cooperate to immobilize virions for relatively long time periods. First, using a clustering analysis, we observed a clear separation between two classes of virion behavior: freely diffusing and immobilized. While the proportion of freely diffusing virions decreased with antibody concentration, the magnitude of their diffusivity did not, implying an all-or-nothing dichotomy in the pathwise effect of the antibodies. Proceeding under the assumption that all binding events are reversible, we used a novel switch-point detection method to conclude that there are very few, if any, state switches on the experimental timescale of 20 s. To understand this slow state switching, we analyzed a recently proposed continuous-time Markov chain model for binding kinetics and virion movement. Model analysis implied that virion immobilization requires cooperation by multiple antibodies that are simultaneously bound to the virion and mucin matrix and that there is an entanglement phenomenon that accelerates antibody-mucin binding when a virion is immobilized. In addition to developing a widely applicable framework for analyzing multistate particle behavior, this work substantially enhances our mechanistic understanding of how antibodies can reinforce a mucus barrier against passive invasive species.

Cervical Local Immune Response for High-Risk Human Papillomavirus Infection: Involvement With Cervical Mucus SLPI Proteins.

PURPOSE: To evaluate cervical mucus secretory leukocyte protease inhibitor (SLPI) concentrations in patients with high-risk human papillomavirus (hrHPV) 16 or 18 positive and low-grade squamous intraepithelial lesions (LGSIL) or high-grade squamous intraepithelial lesions (HGSIL). METHOD: Patients with HPV 16 or 18 positive from 30 to 45 years of age whose cervical cancer screening results reported cytologically LGSIL or HGSIL were included in the study. In the control group, we included participants in the same age with cytology negative and HPV-negative healthy women. All cytological LGSIL or HGSIL results were histopathologically confirmed with colposcopic biopsy specimens. Finally, the study consisted of a total of 3 groups each containing 25 participants as follows: (1) Pap smear and HPV-negative control group, (2) HPV 16 or HPV 18 and LGSIL-positive participants, and (3) HPV 16 or 18 and HGSIL-positive participants. Cervical mucus SLPI levels were analyzed using the enzyme-linked immunosorbent assay method. RESULTS: The mean cervical mucus SLPI levels were 32.94 ng/mL (range: 23-41.29 ng/mL) in the hrHPV + LGSIL group, 29.40 ng/mL (range: 21.03-38.95 ng/mL) in the hrHPV + HGSIL, and 18.75 ng/mL (range: 13.58-29.24 ng/mL) in the healthy control group. Cervical mucus SLPI levels were found to be significantly higher in the hrHPV + LGSIL and hrHPV + HGSIL groups compared to the control group ( P < .001). CONCLUSIONS: The data from the present study indicate that SLPI seems to be one of the important immunomodulatory proteins that provide local immune response in cervical mucosa.

The role of the cervix in fertility: is it time for a reappraisal?

Knowledge regarding the role of the cervix in fertility has expanded considerably over the past 20 years and in this article, we propose that it is now time for its function to be reappraised. First, we review the anatomy of the cervix and the vaginal ecosystem that it inhabits. Then, we examine the physiology and the role of the cervical mucus. The ongoing mystery of the exact mechanism of the sperm-cervical mucus interaction is reviewed and the key players that may unlock this mystery in the future are discussed. The soluble and cellular biomarkers of the lower female genital tract which are slowly being defined by contemporary research are reviewed. Attempts to standardize these markers, in this milieu, are hindered by the changes that may be attributed to endogenous or exogenous factors such as: age, hormonal changes during the menstrual cycle, ectropion, infection, smoking and exposure to semen during sexual intercourse. We review what is known about the immunology of the cervix. With the widespread use of large loop excision of the transformation zone (LLETZ) for treatment of cervical intraepithelial neoplasia, the anatomy of the cervix is changing for many women. While LLETZ surgery has had very positive effects in the fight against cervical cancer, we debate the impact it could have on a woman's fertility.

[Cytokine status of cervical mucus in women with transitory and persistent course of papillomavirus infection].

AIM: Study the levels of cytokines in cervical mucus of women with transitory and persistent course of papillomavirus infection (PVI). MATERIALS AND METHODS: Material from 122 women was studied: 32 patients in control group, 68 patients with transitory course of PVI and 52 women with persistent course of PVI. The presence or absence of high risk HPV DNA was confirmed by real time PCR. High risk HPV DNA was determined in scrapes of epithelial cells of cervical canal. Quantitative determination of cytokines (IFN-alpha, IFN-gamma, IL-1beta, receptor antagonist IL-1, IL-2, IL-4, IL-8 and IL-10, TNFalpha in cervical mucus was performed by enzyme immunoassay. RESULTS: Transitory course of PVI was characterized by an increase of IFN-alpha and IFN-gamma, persistent course of PIV--by a decrease of IFN-alpha, IL-2 level was increased in both groups of patients with PVI. CONCLUSION: The outcome of PVI is controlled by interferon component of the immunity. Because of this during observation of patients with PVI the determination of IFN-alpha, IFN-gamma content in cervical mucus is an appropriate diagnostic procedure in clinical practice for the prognosis of risk of development of high risk PIV persistency.

Immunomodulatory factors in cervicovaginal secretions from pregnant and non-pregnant women: a cross-sectional study.

BACKGROUND: Pregnant women are at an increased risk for HIV infection due to unknown biological causes. Given the strong effect of sex-hormones on the expression of immunomuodulatory factors, the central role of mucosal immunity in HIV pathogenesis and the lack of previous studies, we here tested for differences in immunomuodulatory factors in cervico-vaginal secretions between pregnant and non-pregnant women. METHODS: We compared concentrations of 39 immunomodulatory factors in cervicovaginal lavages (CVL) from 21 pregnant women to those of 24 non-pregnant healthy women from the US. We used Bonferroni correction to correct for multiple testing and linear regression modeling to adjust for possible confounding by plasma cytokine concentration, cervical ectopy, total protein concentration, and other possible confounders. Cervical ectopy was determined by planimetry. Concentration of immunomodulatory factors were measured by a multiplex assay, protein concentration by the Bradford Method. RESULTS: Twenty six (66%) of the 39 measured immunomodulatory factors were detectable in at least half of the CVL samples included in the study. Pregnant women had threefold lower CVL concentration of CCL22 (geometric mean: 29.6 pg/ml versus 89.7 pg/ml, p = 0.0011) than non-pregnant women. CVL CCL22 concentration additionally correlated negatively with gestational age (Spearman correlation coefficient [RS]: -0.49, p = 0.0006). These associations remained significant when corrected for multiple testing. CCL22 concentration in CVL was positively correlated with age and negatively correlated with time since last coitus and the size of cervical ectopy. However, none of these associations could explain the difference of CCL22 concentration between pregnant and non-pregnant women in this study, which remained significant in adjusted analysis. CONCLUSIONS: In this study population, pregnancy is associated with reduced concentrations of CCL22 in cervicovaginal secretions. The role of CCL22 on HIV transmission should now be investigated in prospective studies.

[Comparative evaluation of indicators of local, humoral immunity and nonspecific resistance in patients with different pathology of the cervix].

A comparative evaluation of some indicators of immune system and analysis of the dependence of these parameters (correlation) are carried out to identify interrelated mechanisms. The observed changes in the concentrations of indicators of immune system and the correlation between cytokines, humoral immunity and nonspecific resistance in cervical mucus in patients with cervical pathology demonstrate the complex, interrelated and changing interactions of the local immune system at various stages of development of the pathological process of the cervix.

Secretory leukocyte protease inhibitor and progranulin as possible regulators of cervical remodeling in pregnancy.

Secretory leukocyte protease inhibitor (SLPI) and progranulin (PGRN) are secretory proteins with an anti-inflammatory property. Their involvement in cervical remodeling in pregnant uterus is not yet elucidated. Thus, this study aimed to explore the significance of SLPI and PGRN in the maintenance of pregnancy by investigating the factors associated with their expression levels at the cervix. Concentrations of SLPI and PGRN proteins were measured in cervical mucus samples collected from asymptomatic pregnant women at 24-26 weeks of gestation (n = 166). The concentrations of those molecules were analyzed with clinical parameters related to risk for preterm delivery (PD). In pregnant mice, we evaluated the effect of lipopolysaccharide-induced inflammation and progesterone effect modulation on cervical mRNA expression of SLPI and PGRN. The cervical PGRN level was significantly lower in women with short cervix (<35 mm) and with a history of threatened PD. In women with short cervix, cervical SLPI concentrations were positively correlated with inflammatory cytokines, interleukin-6 (R2 = 0.75) and interleukin-8 (R2 = 0.71). In pregnant mice, cervical mRNA expressions of PGRN and SLPI were increased in response to progesterone supplementation and were suppressed by a progesterone antagonist, mifepristone. Lipopolysaccharide-induced inflammation caused remarkable upregulation in cervical SLPI mRNA level but not in PGRN. Progesterone and local inflammation are the factors controlling expression levels of PGRN and SLPI at the cervix. The observed relationship of PGRN and SLPI levels in the cervical mucus with PD-related clinical parameters supports that those anti-inflammatory molecules possibly play a significant role in appropriate regulation of cervical remodeling.

Antisperm antibodies and human reproduction.

PURPOSE: To present strategies in diagnosing and treating infertility related to antisperm antibodies. METHODS: Antisperm antibodies (ASA) were detected on sperm using the direct immunobead (IBD) test. Treatments included intrauterine insemination (IUI) with pretreatment with chymotrypsin/galactose vs. in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). RESULTS: Intrauterine insemination with protein digestive enzyme treatment was much more effective than IUI without enzymatic therapy. However IVF with ICSI provided three times the pregnancy rate for males with sperm coated with ASA than IUI with chymotrypsin treated sperm. CONCLUSIONS: It is advisable to include measurement for ASA on the initial semen analysis. However, another option is to perform it initially only with an abnormal post-coital test. The decision for IUI with chymotrypsin pretreatment of the sperm vs. IVF with ICSI may depend on insurance and financial issues.

[Local sperm antibodies and general levels of immunoglobulins in ovulatory cervical mucus]. / Lokální protilátky proti spermiím a celkové hladiny imunoglobulinu v ovulacním cervikálním hlenu.

OBJECTIVE: The aim of our preliminary study was to compare the levels of total local sIgA and IgG with activity of detected sperm antibodies in ovulatory cervical mucus (OCM). SETTING: Department of Gyneacology and Obstetrics, Medical School and Faculty Hospital, Charles University, Plzen. METHODS: We screened samples of OCM from 12 pacients aged 26-31 (29,6 years on average) by radial immunodifusion (RID) to determine s IgA and IgG. Indirect MAR test was used for detection of spermagglutinationg antibodies. RESULTS: We found out by RID the average concentration of sIgA in OCM 567,84 mg/l (0 -1250,47) and the average concentration of IgG in OCM 23,57 mg/l (8,74-47,99). Antibody activity against sperm cells dominates in IgA with 6 pacients, in IgA with 1 patient, in IgA and IgG together with 1 infertile woman and in IgA and IgM isotypes together with 1 patient. No local sperm antibodies were determined with 3 patients. CONCLUSION: We proved the hypothesis, that the levels of spermagglutinating antibodies do not correlate with findings of total sIgA and IgG in OCM with our patients.

Activation of the Complement System in the Lower Genital Tract During Pregnancy and Delivery.

Background: Human pregnancy alters profoundly the immune system. The local involvement and mechanisms of activation of the complement system in the cervicovaginal milieu during pregnancy and delivery remain unexplored. Objectives: To determine whether normal pregnancy and delivery are associated with local activation of complement or changes in the immunoglobulin profile in the cervix. Study Design: This study was designed to assess IgA, IgG, and complement activation in the cervicovaginal area in three groups of patients: i) 49 pregnant women (week 41+3-42+0) not in active labor, ii) 24 women in active labor (38+4-42+2), and iii) a control group of nonpregnant women (n=23) at child-bearing age. We collected mucosal samples from the lateral fornix of the vagina and external cervix during routine visits and delivery. The Western blot technique was used to detect complement C3 and its activation products. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and analyzed. IgA and IgG were analyzed by Western blotting and quantified by ELISA. One-way ANOVA and Tukey's Multiple Comparison tests were used for statistical comparisons. Results: A higher abundance but lower activation level of C3 in both the external cervix (P<0.001) and lateral fornix of the vagina (P<0.001) was observed during delivery (58 ± 22, n= 24) in comparison to the groups of nonpregnant (72 ± 13%; mean ± SD, n=23) and pregnant women (78 ± 22%, n=49). Complement activating IgG was detected in higher abundance than IgA in the cervicovaginal secretions of pregnant women. In a small proportion samples also C3-IgG complexes were detected. Conclusions: Our results reveal an unexpectedly strong activation of the complement system and the presence IgG immunoglobulins in the cervicovaginal area during pregnancy, active labor, and among nonpregnant women. In contrast to the higher amounts of C3 in the cervicovaginal secretions during labor, its activation level was lower. Complement activating IgG was detected in higher concentrations than IgA in the mucosal secretions during pregnancy and labor. Taken together our results imply the presence a locally operating humoral immune system in the cervicovaginal mucosa.

The cervical mucus plug: structured review of the literature.

The cervical mucus plug is a large, complex structure within the cervical canal that is shed shortly before or during labor. We propose that the cervical mucus plug fulfills critical 'gate-keeper' functions based on its physical and immunologic properties, which help prevent ascending infection and preterm labor. The viscoelastic properties of the cervical mucus plug are determined by mucins (large glycoproteins), which can inhibit viral replication and exclude larger molecules and bacteria by preventing their diffusion through the plug. Furthermore, the innate and adaptive immunological properties of the cervical mucus plug are well suited for arresting bacterial infection by stimulating a robust inflammatory response. A possible association between an impaired gate-keeper function of the cervical mucus plug and preterm birth is discussed.

Human sperm quality and lipid content after migration into normal ovulatory human cervical mucus containing low numbers of leukocytes.

The aim of this study was to investigate whether a relationship exists between the presence of low numbers of leukocytes in normal ovulatory cervical mucus and sperm quality and lipid content after migration. The percentages of live, motile and morphologically normal spermatozoa, movement parameters assessed by computer-aided sperm analysis (CASA), and ionophore-induced acrosome reaction measured by flow cytometry were determined before and after migration. High-performance liquid chromatography with ultraviolet detection was used to measure the sperm lipid content, including the various diacyl subspecies. The number of leukocytes found in solubilized mucus samples was counted using a haemocytometric method. Overall, the presence of leukocytes in the cervical mucus samples did not significantly influence sperm motility and morphology, sperm kinematic parameters, or the sperm content in sphingomyelin or cholesterol. In contrast, after migration, the decrease in various sperm diacyls and the level of induced acrosome reaction was significantly less pronounced in mucus samples containing>or=10(4) leukocytes than in mucus samples with no or rare leukocytes whereas the level of induced acrosome reaction was higher. The present data suggest that the low level of leukocytes found in normal ovulatory cervical mucus could influence the process of sperm lipid remodelling/capacitation.

The lower genital tract microbiota in relation to cytokine-, SLPI- and endotoxin levels: application of checkerboard DNA-DNA hybridization (CDH).

In the present study the lower genital tract microbiota in asymptomatic fertile women (n=34) was identified and quantified by culturing vaginal secretions. Also, vaginal and cervical samples were analyzed by a semiquantitative checkerboard DNA-DNA hybridization technique (CDH) based on genomic probes prepared from 13 bacterial species (Bacteroides ureolyticus, Escherichia coli, Fusobacterium nucleatum, Gardnerella vaginalis, Mobiluncus curtisii ss curtisii, Prevotella bivia, Prevotella disiens, Prevotella melaninogenica, Atopobium vaginae, Lactobacillus iners, Staphylococcus aureus ss aureus, Streptococcus anginosus, and Streptococcus agalactiae). The bacterial species found by either culture or CDH were correlated with proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-8), secretory leukocyte protease inhibitor (SLPI), and endotoxin in the cervicovaginal samples. Grading the women into healthy, intermediate, or bacterial vaginosis (BV) as based on Gram staining of vaginal smears, the viable counts of lactobacilli (L. gasseri) and of streptococci-staphylococci combined were highest in the intermediate group. In BV, particularly the high concentrations of Actinomyces urogenitalis, Atopobium vaginae, and Peptoniphilus harei were noted (>or=10(11) per ml). The total viable counts correlated with both cervical IL-1 alpha and IL-1 beta. A strong negative correlation was observed between L. iners and total viable counts, G. vaginalis, or cervical IL-1 alpha, while it correlated positively with SLPI. Analysis of vaginal and cervical samples from 26 out of the 34 women by CDH showed that anaerobic bacteria were more frequently detected by CDH compared to culture. By this method, A. vaginae correlated with G. vaginalis, and L. iners with S. aureus. With regard to cytokines, B. ureolyticus correlated with both cervical and vaginal IL-1 alpha as well as with cervical IL-8, while F. nucleatum, S. agalactiae, S. anginosus, or S. aureus correlated with vaginal IL-1 alpha. Furthermore, all Gram-negative bacteria taken together, as measured by CDH, correlated with vaginal endotoxin and inversely with vaginal SLPI. The significance of the results is discussed. In summary, mapping of the identity and quantity of vaginal bacterial species and their association with locally produced host innate immune factors will help in defining various types of abnormal vaginal microbiota, developing new ways of assessing the risk of ascending subclinical infections, and in treating them. CDH appears to be a suitable tool for future analyses of large numbers of clinical samples with an extended number of bacterial probes.

The inhibition of the Human Immunodeficiency Virus type 1 activity by crude and purified human pregnancy plug mucus and mucins in an inhibition assay.

BACKGROUND: The female reproductive tract is amongst the main routes for Human Immunodeficiency Virus (HIV) transmission. Cervical mucus however is known to protect the female reproductive tract from bacterial invasion and fluid loss and regulates and facilitates sperm transport to the upper reproductive tract. The purpose of this study was to purify and characterize pregnancy plug mucins and determine their anti-HIV-1 activity in an HIV inhibition assay. METHODS: Pregnancy plug mucins were purified by caesium chloride density-gradient ultra-centrifugation and characterized by Western blotting analysis. The anti-HIV-1 activities of the crude pregnancy plug mucus and purified pregnancy plug mucins was determined by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells). RESULTS: The pregnancy plug mucus had MUC1, MUC2, MUC5AC and MUC5B. The HIV inhibition assay revealed that while the purified pregnancy plug mucins inhibit HIV-1 activity by approximately 97.5%, the crude pregnancy plug mucus failed to inhibit HIV-1 activity. CONCLUSION: Although it is not clear why the crude sample did not inhibit HIV-1 activity, it may be that the amount of mucins in the crude pregnancy plug mucus (which contains water, mucins, lipids, nucleic acids, lactoferrin, lysozyme, immunoglobulins and ions), is insufficient to cause viral inhibition or aggregation.

Comparative histopathology and antibody responses of non-Tritrichomonas foetus trichomonad and Tritrichomonas foetus genital infections in virgin heifers.

The potential pathogenicity of non-Tritrichomonas foetus trichomonads (NTfTs) recently isolated from the prepuce of virgin bulls is not known. The purpose of this study was to determine the ability of these NTfTs to cause disease in the female reproductive tract relative to T. foetus. Forty-four virgin heifers were experimentally infected intravaginally with either one of two NTfTs (Pentatrichomonas hominis or Tetratrichomonas spp.), T. foetus, or sterile media and cultured weekly from 0 time until slaughter at 8 weeks. Serum and vaginal antibody responses during infection were assessed, and the reproductive tracts were histologically examined, scored, and compared based on numbers of neutrophils, eosinophils, lymphocytes, and plasma cells as well as the qualitative appearance of the reproductive tract. The NTfTs did not persist in the reproductive tract, while T. foetus persisted for at least 6-8 weeks. Further, no vaginal IgA response to infection was found in NTfT-infected and control heifers, but a vaginal IgA response was present in the T. foetus-infected group. Heifers infected with NTfT or controls showed little mucosal inflammatory response compared to T. foetus-infected heifers. Among the trichomonads studied, persistent infection by T. foetus alone seems responsible for uterine inflammatory lesions usually associated with pregnancy loss. The NTfTs studied in this work only transiently infected the vagina and were associated with strictly mild inflammatory changes, which probably do not cause significant disease, i.e., pregnancy loss.

Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition.

IgG possesses an important yet little recognized effector function in mucus. IgG bound to viral surface can immobilize otherwise readily diffusive viruses to the mucin matrix, excluding them from contacting target cells and facilitating their elimination by natural mucus clearance mechanisms. Cervicovaginal mucus (CVM) is populated by a microbial community, and its viscoelastic and barrier properties can vary substantially not only across the menstrual cycle, but also in women with distinct microbiota. How these variations impact the "muco-trapping" effector function of IgGs remains poorly understood. Here we obtained multiple fresh, undiluted CVM specimens (n = 82 unique specimens) from six women over time, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent Herpes Simplex Viruses (HSV-1) in CVM treated with different HSV-1-binding IgG. The IgG trapping potency was then correlated to the menstrual cycle, and the vaginal microbial composition was determined by 16 s rRNA. In the specimens studied, both polyclonal and monoclonal HSV-1-binding IgG appeared to consistently and effectively trap HSV-1 in CVM obtained at different times of the menstrual cycle and containing a diverse spectrum of commensals, including G. vaginalis-dominant microbiota. Our findings underscore the potential broad utility of this "muco-trapping" effector function of IgG to reinforce the vaginal mucosal defense, and motivates further investigation of passive immunization of the vagina as a strategy to protect against vaginally transmitted infections.

Cervico-vaginal mucus (CVM) - an accessible source of immunologically informative biomolecules.

Cervico-vaginal mucus (CVM), the product of epithelial cells lining the uterus, cervix and vagina, is secreted to facilitate uterine lubrication and microbial clearance. Predominantly composed of water and mucins, CVM also contains high levels of immuno-active proteins such as immunoglobulin A (IgA), lactoferrin and lysozyme which protect against infection by blocking adhesion and mediating microbial killing. The repertoire of cytokines, chemokines and antimicrobial peptides is predominantly generated by the secretions of endometrial epithelial cells into the uterine lumen and concentrated in the CVM. The quantity and relative proportions of these inflammatory biomarkers are affected by diverse factors including the estrus cycle and health status of the animal and therefore potentially provide important diagnostic and prognostic indicators. We propose that measuring molecular signatures in bovine CVM could be a useful approach to identifying and monitoring genital tract pathologies in beef and dairy cows.

Detection of autoantibodies to survivin in cervical mucus from patients with human papillomavirus-associated cervical cancer and precursor lesions.

OBJECTIVES: To investigate the prevalence of mucosal autoantibodies to survivin in patients with human papillomavirus (HPV)-associated cervical cancer and precursor lesions. METHODS: Cervical mucus from 117 HPV-associated cervical cancer, 102 high-grade squamous intraepithelial lesion (HSIL), 107 low-grade SIL (LSIL), and 80 normal controls were tested by ELISA using either full length recombinant survivin or survivin-derived peptides. Survivin expression in cervical tissue biopsies was studied by Western Blotting. RESULTS: Cervical mucus from 33 cervical cancer (28.2%), 17 HSIL (16.6%), and 8 LSIL (7.4%) patients reacted with recombinant survivin. The IgA-class antibody response was significantly higher than that observed in the normal controls. The level of mucosal anti-survivin response was associated to the level and intensity of survivin expression in the different lesions. Finally, reactivity against a survivin Nt-derived peptide was found more frequently than reactivity against a Ct-derived peptide. CONCLUSIONS: IgA-class autoantibodies against survivin are present in a substantial proportion of cervical mucus from patients with HPV-associated cervical cancer, and precursor lesions. Mucosal anti-survivin response is positively associated with the level of survivin expression and the grade of cervical lesion.

[Are the antibodies against laminin-1 the signifikant marker of decreased fertility in women?]. / Jsou protilátky proti lamininu-1 významným markerem snízené plodnosti u zen?

OBJECTIVE: Study of antibodies against laminin-1 in IgG in patients with habitual abortion. DESIGN: Prospective study. METHODS: Commercial ELISA method for detection of IgG antibodies against laminin-1 in ovulatory cervical mucus, in sera in women with repeated spontaneous abortions, in sera in patients during spontaneous miscarriages. RESULTS: Positive levels of antibodies against laminine-1 in IgG in sera were found in patients during spontaneous abortions, as to ovulatory mucus of infertile women in time out of pregnancy, we did not find any positivity, only in one serum sample in patient with three pregnancy losses in her history. CONCLUSION: Antibodies against adhesive molecule as laminin-1 presents, can participate during diagnosis of repated spontaneous miscarriages in context of neuro-endocrinne-immune dysregulation, which is not seen during physiological pregnancy.

Cervical mucus and contraception: what we know and what we don't.

OBJECTIVES: Cervical mucus varies in response to both natural and artificial hormonal changes. It is commonly believed that cervical mucus thinning is associated with normal fertility and that progestogen-induced thickening is an essential contraceptive mechanism. This review aims to broadly summarize our current knowledge about cervical mucus from both a clinical and basic research perspective. STUDY DESIGN: We reviewed published literature pertinent to cervical mucus and contraception across scientific disciplines. We first present the most current understanding of the composition of cervical mucus, how it is hormonally regulated, and examine the role of mucus as an immune barrier. We then critically assess the current clinical tests used as surrogate markers for a contraceptive effect. Finally, we review contraceptive studies that have specifically focused on cervical mucus changes. RESULTS: Existing research suggests that cervical mucus has potential to be a contraceptive target with unique, multipurpose characteristics. However, methodologic limitations associated with clinical assessments of cervical mucus complicate our understanding of contraceptive treatment effects. Key pathways involved in cervical mucus production with potential as novel nonhormonal contraceptive targets have been identified. CONCLUSIONS: More research is needed to clarify the role of cervical mucus in current hormonal contraceptives and to support the development of novel nonhormonal cervix-based methods.