Sperm Antibodies Research Articles

Varicocele and testicular cord torsion: immune testicular microenvironment imbalance

The main functions of the testis, steroidogenesis and spermatogenesis, depend on the endocrine axis and systemic and local tolerance mechanisms. Infectious or non-infectious diseases may disturb testicular immune regulation causing infertility. Literature has illustrated that bacterial and viral infections lead to autoimmune infertility: either sperm antibodies or autoimmune epidydimo-orchitis. However, little is known about the association between non-infectious testicular pathologic diseases and autoimmunity. Here we review the novel aspect of varicocele and testicular cord torsion pathology linked to inflammation and discuss how immune factors could contribute to or modulate autoimmunity in ipsi- and contralateral testis.

Relationship between antisperm antibodies and seminogram characteristics

Background: Autoimmunity to spermatozoa could compromise male fertility in at least three fundamental areas: Interfering with the creation of normal amounts of spermatozoa, decreasing their ability to migrate, and impairing their ability to engage with ovum. Objective: This study's objective was to assess the association between infertile male individuals' seminogram features and the existence of antisperm antibodies. Material and Methods: In the present study semen analysis was done by sperm quality analyzer II CP and antisperm antibody by varelisa sperm antibodies enzyme immunoassay kit. Statistical Analysis: The data obtained was analyzed by using mean + standard deviation and chi-square test. Results: The presence of antisperm antibodies in the serum of infertile male was statistically not significant with their seminogram characteristics. Conclusion: Presence of antisperm antibodies in serum of subjects with different seminogram characteristics without any significant difference proved that ASA may not be involved directly in affecting seminogram parameters.

The impact of metalloestrogens on the physiology of male reproductive health as a current problem of the XXI century.

In the XXIst century in highly developed countries, progressively decreasing male reproductive potential is indicated. In recent years epidemiological studies indicate the deterioration of semen parameters: reduction of ejaculate volume, sperm count, and mobility, as well as abnormalities in their morphology. Male infertility can result from many different agents, such as: anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins and development of sperm antibodies and lifestyle (especially obesity, heat and tobacco smoking). It is well documented that adverse changes in male fertility also seem to be associated with environmental exposure to different substances, especially endocrine active factors, known as xenoestrogens, and among these metal ions, known as metalloestrogens, are very important. The role of some metalloestrogens in various diseases, both in women and men, is known and particularly well-proven in women, but still little is known about their role in the regulation of male reproductive potential. Thus we decided to analyse the available information exploring this problem. The review was carried out using the Medline and Google Scholar databases, using the keywords: xenoestrogens, metalloestrogens, male fertility, semen quality, male reproductive potential, mechanisms of metalloestrogen action, environmental pollution and the name of the particular metal. Articles published between 2000 - 2019 have been taken into account, including human and vertebrate animal studies and cell lines. The aim of this review is to discuss the role and mechanisms of action of fifteen metalloestrogens in the human organism, as well as in animal models, and cell cultures, paying special attention to their influence on the physiology of male reproductive health, according to the current state of knowledge. The role of certain metals in human reproduction is still poorly investigated and for some of them only single studies are available. Many factors in our daily lives have a significant impact on male fertility, therefore education is necessary on the threats and how they may be eliminated as far as possible.

Evolution of Sperm Testing-A Bright Future?

We began work on the development of a microfluidic sperm chip in the early 1990s as part of a larger project that developed chips for a wide range of diagnostic tests. Our rationale in developing the sperm chip was to provide an easy-to-use disposable test device for assessing semen quality (e.g., motility) at the point of care as part of the workup of male infertility (Fig. 1, A and B). A more ambitious goal was to provide a range of tests on a single microchip that would assess a series of factors relevant to male fertility testing (e.g., sperm motility and count, sperm–hyaluronic acid interaction, sperm antibodies) (1) (Fig. 1C). Although our sperm studies were targeted toward improving the understanding of fertility in humans, we also had a clear awareness of the implications of an effective sperm selection and testing technology in animal husbandry. Fig. 1. Sperm motility chips. (A) and (B), The silicon chip A enables testing in triplicate, and the scale (1–10) etched next to the channel provides for semiquantitative assessment of progression of sperm along the channel. In the glass chip B, the parallel grooves in the central semen application areas serve to direct sperm toward the curved analytical channels (4 per test), which prevent delay of sperm migration observed for 90° turns (compare with chip A). (C), Semen testing chip (motility, sperm–hyaluronic acid interaction, and 3 areas for other testing). (D), Lithographic mask for various designs of sperm chip and in vitro fertilization (IVF) chips. Mask location 1 …

Male infertility problems of patients with strict sperm morphology between 5–14% may be missed with the current WHO guidelines

Objective: In 2010 W.H.O. changed the lower reference limit for strict sperm morphology from 15 to 4%. The change was based on 5th percentile cut points from a meta-analysis on a published series of fertile men. This study investigates if patients referred for evaluation with sperm morphologies between 5–14% have identifiable etiologies of male infertility.Materials and methods: I.R.B. approval was obtained to review records for patients referred to the University of Michigan Center of Reproductive Medicine between May 2012–May 2014 whom had a sperm morphology of 5–14%. Semen analysis, hormone levels, and information related to an infertility diagnosis, were recorded into a de-identified database. Patients were placed into the categories ‘Varicocele’, ‘Hypogonadism’, ‘Intercourse problems’, ‘Anti-sperm antibodies (A.S.A.)’, ‘Other’ or ‘No diagnosis’.Results: A total of 253 patients were included in the study. Of these, 96/253 (38%) had a clinical varicocele; 44/253 (17%) hypogonadism; 4/253 (2%) intercourse problems; 11/253 (4%) evidence of sperm antibodies; and 15/253 (6%) had various other problems deemed potentially contributing causes of infertility. In all, nearly 67% of the subjects were identified to have a potential contributing etiology of male infertility. Similar results were found for the men with isolated low morphology (n = 194).Conclusions: This study demonstrates that 67% of men in infertile couples, who have strict sperm morphology between 5 and 14%, are found to have a potential contributing male factor infertility diagnosis. This raises the possibility that the new lower reference value for sperm morphology may result in missed opportunities for proper infertility assessment.

Toxicity and Mutagenicity Evaluation Following RISUG Contraception Reversal in Rats.

Reestablishment of fertility, after a male contraceptive method, is of great concern. In this context, RISUG (Reversible Inhibition of Sperm Under Guidance) has been evaluated for its mutagenicity following reversibility with dimethyl sulfoxide (DMSO)/sodium bicarbonate (NaHCO3) in Wistar albino rats. Animals were divided into 7 groups, namely, sham-operated control, vas occlusion with RISUG for 90 and 360 days, reversal with DMSO and NaHCO3 after 90 and 360 days, respectively. The testis, cauda epididymis, cauda epididymal spermatozoa, and serum were evaluated for apoptosis and hormonal status through various assays. RISUG was subjected to Ames test at dose levels of 10, 50, and 100 µL. Results of terminal deoxynucleotidyl transferase nick end labeling and caspase-3 assays in testes and cauda epididymis revealed that the percentage of positive cells in the experimental groups was comparable to sham-operated control. Annexin V assay in cauda epididymal spermatozoa showed slight elevation in group II ( P < 0.05), whereas in the remaining groups, minimum numbers of positive sperms were found. Hormone profile, namely, testosterone, prolactin, cortisol, prostate-specific antigen, and sperm antibody concentration, remained unchanged. In Ames test, no significant increase was observed in the number of revertant colonies on plates containing RISUG in the presence and absence of S9 mix in all 3 strains. Therefore, the reversal of RISUG-induced contraception by solvent vehicle DMSO/NaHCO3 was successful without any toxicity at the cellular levels.

Infectious, inflammatory and 'autoimmune' male factor infertility: how do rodent models inform clinical practice?

BACKGROUNDInfection and inflammation of the reproductive tract are significant causes of male factor infertility. Ascending infections caused by sexually transmitted bacteria or urinary tract pathogens represent the most frequent aetiology of epididymo-orchitis, but viral, haematogenous dissemination is also a contributory factor. Limitations in adequate diagnosis and therapy reflect an obvious need for further understanding of human epididymal and testicular immunopathologies and their contribution to infertility. A major obstacle for advancing our knowledge is the limited access to suitable tissue samples. Similarly, the key events in the inflammatory or autoimmune pathologies affecting human male fertility are poorly amenable to close examination. Moreover, the disease processes generally have occurred long before the patient attends the clinic for fertility assessment. In this regard, data obtained from experimental animal models and respective comparative analyses have shown promise to overcome these restrictions in humans.OBJECTIVE AND RATIONALEThis narrative review will focus on male fertility disturbances caused by infection and inflammation, and the usefulness of the most frequently applied animal models to study these conditions.SEARCH METHODSAn extensive search in Medline database was performed without restrictions until January 2018 using the following search terms: ‘infection’ and/or ‘inflammation’ and ‘testis’ and/or ‘epididymis’, ‘infection’ and/or ‘inflammation’ and ‘male genital tract’, ‘male infertility’, ‘orchitis’, ‘epididymitis’, ‘experimental autoimmune’ and ‘orchitis’ or ‘epididymitis’ or ‘epididymo-orchitis’, antisperm antibodies’, ‘vasectomy’. In addition to that, reference lists of primary and review articles were reviewed for additional publications independently by each author. Selected articles were verified by each two separate authors and discrepancies discussed within the team.OUTCOMESThere is clear evidence that models mimicking testicular and/or epididymal inflammation and infection have been instructive in a better understanding of the mechanisms of disease initiation and progression. In this regard, rodent models of acute bacterial epididymitis best reflect the clinical situation in terms of mimicking the infection pathway, pathogens selected and the damage, such as fibrotic transformation, observed. Similarly, animal models of acute testicular and epididymal inflammation using lipopolysaccharides show impairment of reproduction, endocrine function and histological tissue architecture, also seen in men. Autoimmune responses can be studied in models of experimental autoimmune orchitis (EAO) and vasectomy. In particular, the early stages of EAO development showing inflammatory responses in the form of peritubular lymphocytic infiltrates, thickening of the lamina propria of affected tubules, production of autoantibodies against testicular antigens or secretion of pro-inflammatory mediators, replicate observations in testicular sperm extraction samples of patients with ‘mixed atrophy’ of spermatogenesis. Vasectomy, in the form of sperm antibodies and chronic inflammation, can also be studied in animal models, providing valuable insights into the human response.WIDER IMPLICATIONSThis is the first comprehensive review of rodent models of both infectious and autoimmune disease of testis/epididymis, and their clinical implications, i.e. their importance in understanding male infertility related to infectious and non-infectious/autoimmune disease of the reproductive organs.

ENDOCRINE PROFILE OF THE MALE POPULATION IN RUSSIA DEPENDING ON THE GEOGRAPHIC LATITUDE OF OCCUPATION

The goal of research is to examine the characteristics of the hormones of the pituitary-gonadal and pituitary-thyroid gland systems in the peripheral blood of the male population living in different areas of Russia, taking into account the population groups. The study involved 136 men aged 22 to 50 years old, who are permanently resident in the North no less than three generations. Among them there are 80 local residents of Arkhangelsk (64° 32' N), 19 local residents of Vologda (59° 13' N) and 37 local residents of Nes, Nenets Autonomous Okrug (66° 36' N). According to the basis of nationality group of men living in Nes was divided into: Russian - 23 people and settled aboriginal population (Nenets, Komi) - 14 people. We have shown that functional activity of the pituitary-thyroid axis (thyrotropin, thyroxine, free triiodothyronine) in the male Caucasoid and settled aboriginal population of the polar region exceeds its level in the inhabitants of the circumpolar area (Arkhangelsk). At the same time, men living in the mid-latitude area (Vologda) had minimal activity of the pituitary-thyroid axis (triiodothyronine, free thyroxine), compared with polar and circumpolar areas. It was shown that the functional activity of the pituitary-gonadal axis in men living in Vologda (luteinizing hormone, follicle-stimulating hormone, inhibin B, free testosterone, dehydroepiandrosterone sulfate) and in Nes (follicle-stimulating hormone, inhibin B, testosterone, free testosterone, sex-hormone-binding globuline) was higher compared with the inhabitants of the city of Arkhangelsk. The levels of sperm antibodies were minimal in men living in Nes. At the same time, changing the traditional way of life from nomadic to a settled one leads to the negative tendencies such as the decrease of the synthesis reserves of steroid hormones in the settled aboriginal population that is shown by the decreased serum levels of progesterone and dehydroepiandrosterone sulfate.

The Epidemiology of Anti-Sperm Antibodies Among Couples with Unexplained Infertility in North West Bank, Palestine.

Anti sperm antibodies (ASA) can present in serum and semen and they may lead to impair the sperms function leading to infertility. The precise mechanism of generation of these antibodies is yet to be discovered. This study was performed to determine the prevalence of anti-sperm antibodies (ASA) in patients with unexplained infertility. The study was initiated also to explore the possible factors that may associate with ASA formation and how ASA status is associated with pregnancy rates after going with in vitro fertilization - intracytoplasmic sperm injection (IVF-ICSI). A cross-sectional study was conducted on 42 normal infertile couples consulting Razan Medical Center for Infertility & I.V.F. in Nablus, Palestine, from December 2012 - March 2013. Serum levels of immunoglobulins G (IgG) ASA were measured in participants (males and females) using enzyme-linked immunosorbent assay (ELISA). In addition, participants also filled a questionnaire about the presence of previous varicocele repair, inguinal hernia repair, orchitis, testicular trauma and vasectomy reversal among males and severe coitus bleeding and coitus during menses or puerperium among females. Couples were also asked about previous IVF-ICSI procedures and the outcome of the procedure in terms of either they got pregnant or not. Data was analysed using SPSS software. The prevalence of ASA was 14.3% (6/42) among all couples, 9.5% (4/42) among males and 4.8% (2/42) among females. There was no significant relationship between previous varicocele repair, previous inguinal hernia repair, or orchitis and formation of ASA (p value =0.64, 0.56, and 0.26 respectively). Previous trauma, vasovasostomy, severe coitus bleeding and coitus during menses or puerperium were not observed in any of the study sample. ASA did not seem to affect the outcome of IVF-ICSI (p-value =0.54). Prevalence of ASA in infertile couples in the north part of Palestine is similar to that obtained worldwide. ASA formation does not relate to any of the studied risk factors and does not seem to associate with pregnancy rate after IVF-ICSI. We recommend further studies using a larger sample size and including all parts of Palestine in order to generalize the obtained results.

Antisperm protein targets in azoospermia men.

BACKGROUND:The number of couples that meet the definition of infertility at reproductive ages is increasing worldwide. One of the most known conditions of infertility in males is azoospermia, defined as complete absence of spermatozoa in the semen. Azoospermia manifests in two forms, namely obstructive and non-obstructive azoospermia. Although the presence of antisperm antibody (ASA) has been reported in 88% of the patients with obstructive azoospermia (OA), interestingly, there is no data regarding ASA targets in OA individuals.AIM:The present study aimed to identify sperm antibody targets in a group of OA men.SETTINGS AND DESIGN:The present study was carried out on 27 OA infertile men and 27 healthy fertile age-matched males as cases and controls, respectively.SUBJECTS AND METHODS:The sperm proteome was separated using two-dimensional gel electrophoresis technique, transferred onto the polyvinylidene fluoride membrane, and blotted with the sera of a group of OA men. Then, it was compared with the membranes blotted with the sera of a group of healthy fertile men. Matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI TOF/TOF) mass spectrometry was used to identify the different blotted spots and finally the results of the mass analysis were confirmed using reverse transcriptase polymerase chain reaction method.RESULTS:The results indicated that OA patients might produce antibody against two sperm proteins, Tektin-2 and triose phosphate isomerase. Moreover, the expressions of the two targeted proteins were confirmed at RNA level.CONCLUSIONS:The findings of the present study revealed two functionally important sperm proteins as antibody targets in azoospermic men.

CLINICAL AND IMMUNOLOGICAL INTERACTIONS IN THE RECURRENT MISCARRIAGEAND THEIR CORRECTION METHODS

The review is devoted to the problem of reproductive losses associated with impairment of the immune mechanisms which ensure the normal pregnancy progression. Increased expression of cytokines by T-helper type 1 cells underlies the immune etiology of reproductive losses. Decrease in regulatory T- cells activity leads to the development of recurrent spontanious abortion . The most important mechanisms of pregnancy progression cytokine regulation are presented. The main autoimmune conditions leading to fetal death are: antiphospholipid syndrome, increased activity of natural killer cells, compatibility in the HLA system, the presence of antinuclear, antigiston, sperm antibodies and Human chorionic gonadotropin antibodies. The modern methods of pathogenetic therapy of recurrent spontanious abortion are reviewed.

Characterization and possible function of glyceraldehyde-3-phosphate dehydrogenase-spermatogenic protein GAPDHS in mammalian sperm.

BackgroundSperm proteins are important for the sperm cell function in fertilization. Some of them are involved in the binding of sperm to the egg. We characterized the acrosomal sperm protein detected by a monoclonal antibody (MoAb) (Hs-8) that was prepared in our laboratory by immunization of BALB/c mice with human ejaculated sperms and we tested the possible role of this protein in the binding assay.MethodsIndirect immunofluorescence and immunogold labelling, gel electrophoresis, Western blotting and protein sequencing were used for Hs-8 antigen characterization. Functional analysis of GAPDHS from the sperm acrosome was performed in the boar model using sperm/zona pellucida binding assay.ResultsMonoclonal antibody Hs-8 is an anti-human sperm antibody that cross-reacts with the Hs-8-related protein in spermatozoa of other mammalian species (boar, mouse). In the immunofluorescence test, Hs-8 antibody recognized the protein localized in the acrosomal part of the sperm head and in the principal piece of the sperm flagellum. In immunoblotting test, MoAb Hs-8 labelled a protein of 45 kDa in the extract of human sperm. Sequence analysis identified protein Hs-8 as GAPDHS (glyceraldehyde 3-phosphate dehydrohenase-spermatogenic). For this reason, commercial mouse anti-GAPDHS MoAb was applied in control tests. Both antibodies showed similar staining patterns in immunofluorescence tests, in electron microscopy and in immunoblot analysis. Moreover, both Hs-8 and anti-GAPDHS antibodies blocked sperm/zona pellucida binding.ConclusionGAPDHS is a sperm-specific glycolytic enzyme involved in energy production during spermatogenesis and sperm motility; its role in the sperm head is unknown. In this study, we identified the antigen with Hs8 antibody and confirmed its localization in the apical part of the sperm head in addition to the principal piece of the flagellum. In an indirect binding assay, we confirmed the potential role of GAPDHS as a binding protein that is involved in the secondary sperm/oocyte binding.

Immunodominant Semen Proteins III : IgG1 and IgG4 Linkage in Female Immune Infertility

Active immune mechanism in the female reproductive tract may produce high levels of anti-seminal/sperm antibodies. Generated antibodies in the process of isoimmunization seem to be associated with female immune infertility. The aim of our study consists in the profiling of specific serum immunoglobulin classes and subclasses in infertile women. We focus on the distribution of serum seminal/sperm-specific antibodies in order to find those apparently related to female isoimmunization. Immunoglobulins G1-4, A1,2, M and E were measured by ELISA in serum from 30 infertile and 10 fertile females. Anti-seminal/sperm IgG1 and IgG4 fractions were predominantly detected. Anti-seminal IgG1 and IgG4 were observed approximately in the 2:1 ratio, anti-sperm fraction in the 1:2 ratio. Strikingly, the approximate ratio between IgG1 and IgG2 was 3:1 in seminal specific and 2:1 in sperm specific antibodies. Surprisingly, IgG3 antibodies were nearly negative for both antigen fractions, seminal and sperm. Concerning our results, the proportionality does exist between seminal and sperm antibody fractions. Based on the poorly detectable levels of semen specific IgE, M, A1,2, G3, the markers of pathologic female isoimmunization appear to be the serum IgG1 and IgG4. These preliminary findings may contribute to a detailed patient diagnosis and an improved therapy.

STUDY OF THE INFLUENCE OF SPERM ANTOBODIES ON SPERM CHARACTERISTICS

Event Abstract Back to Event STUDY OF THE INFLUENCE OF SPERM ANTOBODIES ON SPERM CHARACTERISTICS Anatoliy P. Godovalov1*, Tatyana Y. Danielyan2, Liliya P. Bykova3 and Mikhail V. Smirnov1 1 Acad. E.A. Wagner Perm State Medical University, immunology, Russia 2 Ltd. Medical Studio, Russia 3 Acad. E.A. Wagner Perm State Medical University, microbiology and virology, Russia It is known that about 15% of couples suffer from infertility, with a third of cases due to male infertility (Carr, 2013). According to the observations of several authors, the quality of sperm is changing in the last decade, that is due to reduction of sperm concentration and motility (Carr, 2013). One of the factors affecting the sperm may be immune effector molecules, such as antibodies. It is shown that sperm antibodies can affect sperm parameters (Cui et al., 2015). Unfortunately, it was not possible to identify the leading antigen to which the sperm antibodies are formed, and the animal experiments showed the role of complex antigens in stimulation of antibody formation (Carr, 2013; Cui et al., 2015). Causes of these antibodies formation, as well as the mechanisms of their negative impact on sperm are understudied (Cui et al., 2015). The purpose of the research was to study the characteristics of sperm in case of sperm antibodies detection in the semen. Materials and methods. Semen samples from 71 men, mean age was 37.7±0.7 years, were analyzed. Term from onset of sexual activity without protection until the study averaged 42 months. Taking material and study of sperm was performed according standardized procedures suggested by WHO experts (2010). Determination of the concentration of sperm antibodies in semen was performed by ELISA according to the manufacturer's instructions. All the men were divided into two groups, the first one consisted of men with the presence of sperm antibodies in semen, the second one (control group) - men who had no sperm antibodies detected in semen. Statistical analysis was performed using the Student t-test. Results and discussion. In the course of studies it was found that men with sperm antibodies had reduced number of sperm. Thus, the number of cells in the control group of men was 91.41±12.53 million/ml, and men with the presence of sperm antibodies had 47.93±9.17 million/ml (p<0.05) sperm. In addition, there was a reduction of living sperm number up to 43.89±8.60 million/ml (in the control group 75.76±9.43 million/ml; p=0.05). During the study of the motility characteristics of sperm it was found that the first group had significantly fewer cells with rapid progressive motion activity, 9.91±5.67 million/ml (the control group had 30.15±4.08 million/ml; p<0.05). The number of slow-moving sperm and cells with disordered progressive activity was not significantly different in two groups. The number of fixed cells in group of men with sperm antibodies was 19.87±1.08 million/ml, and in the control group – 4.85±1.24 million/ml (p<0.05). The first group had sperm with reduced average linear velocity to 10.67±1.20 μm/s (in the control group 13.57±0.53 μm/s; p<0.05). The presence of sperm antibodies in semen does not significantly affect sperm morphology. The number of sperm with defects in the first group of men was 21.96±3.57 million/ml, and in the control group 30.92±4.10 million/ml (p>0.05). The number of leukocytes in two groups was not significantly different. Men of the first group had significantly more cells of spermatogenesis - (0.75±0.06)%, and men of the control group had (0.47±0.07)% (p<0.05). One of the factors of reproductive failure is contamination of semen by microorganisms (Weng et al., 2014). So, total bacterial count of semen in the first group of men surveyed was 5.33±0.32 log10 CFU/ml, and in the control group – 3.96±0.36 log10 CFU/ml (p<0.05). The first group predominantly had members of Enterobacteriaceae family (69.3% samples), while the control group had Gram-positive cocci (88.8% of samples). Men in the first group had no clinical symptoms associated with infectious and inflammatory diseases. However, the ultrasound examination revealed diffuse changes of the prostate by type of chronic prostatitis in more than half of the cases. It is known that microorganisms have the unique ability to adhere, including sperm cells, which promotes their penetration into the egg cell (Prabha et al., 2010). At this, microorganisms violate the fertilization process and division of the zygote. When placing the microorganisms in human cells, the antibodies form to bacterial antigens, as well as to antigens of human cells. Thus, a massive infection of sperm by opportunistic pathogens probably contributes to the increase in the number of sperm antibodies that destroy the activity of sperm. Conclusion. Studies have shown that sperm antibodies violate some quantitative characteristics of sperm, their motion activity. One possible reason for the formation of a large number of sperm antibodies is probably a massive infection of sperm by opportunistic pathogens.

Detection of the dietary xenoglycan N-glycolylneuraminic acid (Neu5Gc) and anti-Neu5Gc antibodies within reproductive tracts of male and female infertility subjects

Objective: To assess the frequency of dietary xenoglycanNeu5Gc and antibodies in males and females and its impact on fertility. Design: Prospective study of semen, uterine lavage, and follicular fluid from subjects undergoing infertility evaluation or in vitro fertilization (IVF) and fertile controls. Setting: University based infertility program. Participants: Males (n=23) and females (n=27) undergoing semen analysis and saline infusion sonography as part of their diagnostic evaluation and 37 women undergoing IVF were compared to fertile male (n=15) and female (n=14) controls. Intervention: Neu5Gc was measured by affinity purified antibody staining on Western blots, flow cytometry, and by high performance liquid chromatography. Anti- Neu5Gc antibodies were determined by ELISA. Main parameters measured: Frequency and levels of Neu5Gc antigen within sperm and endometrial cells and antibodies in semen, uterine lavage, and follicular fluid. Semen quality and IVF outcomes were assessed between antigen and antibody positive and negative subjects. Results: In infertile subjects,Neu5Gc was detected in 26% of sperm and 54% of endometrial cells compared to 0% in male and 0% female controls. Anti-Neu5Gc antibodies were identified in 54% of seminal fluid, 41% in uterine lavage and 43% of follicular fluid samples. There were no differences in semen parameters, oocyte quality, and embryo development in the presence or absence of Neu5Gc antigen or antibody. However, clinical pregnancy rate was significantly lower in the presence of anti-Neu5Gc antibodies intrauterine lavage (0% vs. 54.5.0%, p<0.05). Conclusions: Neu5Gc and directed antibodies are present in reproductive tracts of both male and female infertility subjects. Our results suggest their presence may interfere with fertility within the uterine environment.

Sperm antibodies, acrosome reaction and anti-Müllerian hormone (AMH) in human semen

The blood–testis barrier is a unique specific system between the Sertoli cells and the basal membrane of the tubuli seminiferi in the testicles that plays a major role in the immune aspects of male fertility. The first part of our presentation shows the basic structure of this intelligent system and the result of its destruction. Mainly inflammatory events, toxic agents, mechanic components, and iatrogenic factors influence the function of the blood–testis barrier, resulting in the formation of anti-sperm antibodies on the surface antigens of the human sperms, thus developing male immune infertility. Anti-sperm antibodies can influence the progressive motility and fertilizing capacity of sperm. It is still a debated issue as to the major role of anti-sperm antibodies in male infertility, especially against a background of repeated miscarriages. To examine this question we performed a prospective clinical trial to observe the suspected role of anti-sperm antibodies in repeated miscarriages. The second part of our paper demonstrates our results, showing no statistically significant impact of anti-sperm antibodies in repeated miscarriages.

To the question of spermatozoa mobility evaluation adjusted for MAR-test results

MAR-test (Mixed agglutination reaction) performs in order to determinate the sperm antibody - Ig G, A and/or M in ejaculate. We calculated the spermatozoa mobility adjusted for MAR- test results. Finally the new approach to the normal MAR- test criteria interpretation in case of spermatozoa mobility parameters between 32 % and 35 % was found out. Even if indicators of spermatozoa mobility are within the range of its normal values - 32, 33, 34 and 35%, the astenozoospermia takes place at values of MAR- test more or equal then 2, 5, 7 and 10% respectively. Finally the range of MAR-test parameters from 0 to 10 % cannot be estimated as a standard normal value if the number of progressively active forms of spermatozoa less than 35 %.

Male urogenital infections: impact of infection and inflammation on ejaculate parameters

Urogenital infections and inflammation may contribute significantly to ejaculate parameters essential for male infertility. For this review, data were acquired by a systematic search of the medical literature of the last 5 years. We address the andrological relevance of male urogenital infections and inflammation on ejaculate parameters. The different classification systems of the WHO and NIH are illustrated. In most cases, a separation of the different areas of the urogenital tract, for example, of the prostate, epididymis and testicles, is not possible. The significance of bacteriospermia with common bacteria is discussed. Furthermore, HIV, ascending chlamydial, mycoplasmal and gonococcal infections are relevant. Especially, the relevance of sexually transmitted microorganisms seems to be underestimated. Leukocytospermia is not well defined in its biological significance. Seminal plasma elastase and the cytokine expression reveal better insights into the inflammatory response of the seminal pathways. Sperm antibodies and reactive oxygen species are not usable as indicators for infection and inflammation. Different aspects for an impairment of ejaculate quality have been demonstrated although a direct ascension of microorganisms to the prostate has not been confirmed. Probably, lesions of the epididymis may sustain an ongoing disturbance of sperm parameters. A potential negative influence of urogenital infections and inflammation on sperm function is under discussion. However, the severity of impairment differs according to the underlying infections and the involved compartments. Signs of infections and inflammation in the ejaculate of infertile men are common, and the relevance is often doubtful in spite of microbiological, spermatological and immunological facilities.

AB0649 Morphofunctional penile alterations with severe sperm abnormalities in antiphospholipid syndrome associated with systemic lupus erythematosus

BackgroundWe identified severe sperm abnormalities associated with intravenous cyclophosphamide (IVCYC) use and reduced penile dimensions with no deleterious effect in erectile function in systemic lupus erythematosus (SLE) patients.1 In contrast,...

Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

Natural immunoglobulin M (IgM) is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC) that contains various elements, including apoptosis inhibitor of macrophage (AIM). Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM(-/-)) mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.