Determination of Intraprostatic and Intratesticular Androgens.

Androgens represent the main hormones responsible for maintaining hormonal balance and function in the prostate and testis. As they are involved in prostate and testicular carcinogenesis, more detailed information of their active concentration at the site of action is required. Since the introduction of the term intracrinology as the local formation of active steroid hormones from inactive precursors of the adrenal gland, mainly dehydroepiandrosterone (DHEA) and DHEA-S, it is evident that blood circulating levels of sex steroid hormones need not reflect their actual concentrations in the tissue. Here, we review and critically evaluate available methods for the analysis of human intraprostatic and intratesticular steroid concentrations. Since analytical approaches have much in common in both tissues, we discuss them together. Preanalytical steps, including various techniques for separation of the analytes, are compared, followed by the end-point measurement. Advantages and disadvantages of chromatography-mass spectrometry (LC-MS, GC-MS), immunoanalytical methods (IA), and hybrid (LC-IA) are discussed. Finally, the clinical information value of the determined steroid hormones is evaluated concerning differentiating between patients with cancer or benign hyperplasia and between patients with different degrees of infertility. Adrenal-derived 11-oxygenated androgens are mentioned as perspective prognostic markers for these purposes.

Long-Term Antitumor Activity and Safety of Enzalutamide Monotherapy in Hormone Naïve Prostate Cancer: 3-Year Open Label Followup Results.

PURPOSE: A phase 2 study of enzalutamide monotherapy in patients with hormone naïve prostate cancer demonstrated high prostate specific antigen response rates at 25 weeks, 1 year and 2 years with minimal effects on total body bone mineral density and favorable safety. In this followup analysis we evaluated enzalutamide antitumor activity and safety at 3 years. MATERIALS AND METHODS: In a single arm analysis 67 patients with hormone naïve prostate cancer and noncastrate testosterone (230 ng/dl or greater) received enzalutamide 160 mg per day orally until disease progression or unacceptable toxicity. The primary end point was the prostate specific antigen response (80% or greater decline from baseline). RESULTS: No patients discontinued treatment during year 3. Of 42 patients with prostate specific antigen assessments at 3 years 38 (90.5%, 95% CI 77.4-97.3) maintained a prostate specific antigen response. Of 26 patients with metastases at baseline 17 (65.4%) had a complete or partial response as the best overall response during 3 years. In patients who completed the 3-year visit minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1-L4 or forearm (range -2.7% to -0.1%). At 3 years total body fat had increased a mean of 16.5%, total lean body mass had decreased a mean of -6.5% and global health status had minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain. CONCLUSIONS: Enzalutamide antitumor activity was maintained in patients with hormone naïve prostate cancer at 3 years. Overall bone mineral density, global health status and safety results were similar to those at 2 years.

Enzalutamide monotherapy in hormone-naive prostate cancer: primary analysis of an open-label, single-arm, phase 2 study.

BACKGROUND: The androgen receptor inhibitor enzalutamide is approved for the treatment of metastatic castration-resistant prostate cancer that has progressed on docetaxel. Our aim was to assess the activity and safety of enzalutamide monotherapy in men with hormone-naive prostate cancer. METHODS: This trial is an ongoing open-label, single-arm, phase 2 study, done across 12 European sites. Men aged over 18 years, with hormone-naive prostate cancer for whom hormone therapy was indicated, and who had non-castration levels of testosterone and prostate-specific antigen (PSA) of 2 ng/mL or greater at screening, and an Eastern Cooperative Oncology Group score of 0, received oral enzalutamide 160 mg/day. The primary outcome was the proportion of patients with an 80% or greater decline in PSA at week 25. All analyses included all patients who had received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT01302041. FINDINGS: 67 men were enrolled into the study. 62 patients (92.5%, 95% CI 86.2-98.8) had a decline in PSA of 80% or greater at week 25. The most commonly reported treatment-emergent adverse events up to week 25 were gynaecomastia (n=24), fatigue (n=23), nipple pain (n=13), and hot flush (n=12), all of which were of mild to moderate severity. Nine patients had a treatment-emergent adverse event of grade 3 or higher, most of which were reported in one patient each, except for pneumonia (grade 3, two patients) and hypertension (grade 3, four patients). Five patients reported serious adverse events, none of which were deemed to be treatment related. INTERPRETATION: Our findings suggest that enzalutamide monotherapy in men with hormone-naive prostate cancer of varying severity provides a level of disease suppression, and was generally well tolerated. These findings provide a rationale for further investigation of clinical response and outcomes with enzalutamide in non-castrate men with prostate cancer.

Epigenetic regulation of transcription and splicing of syncytins, fusogenic glycoproteins of retroviral origin.

Syncytin-1 and -2, human fusogenic glycoproteins encoded by the env genes of the endogenous retroviral loci ERVWE1 and ERVFRDE1, respectively, contribute to the differentiation of multinucleated syncytiotrophoblast in chorionic villi. In non-trophoblastic cells, however, the expression of syncytins has to be suppressed to avoid potential pathogenic effects. We studied the epigenetic suppression of ERVWE1 and ERVFRDE1 5'-long terminal repeats by DNA methylation and chromatin modifications. Immunoprecipitation of the provirus-associated chromatin revealed the H3K9 trimethylation at transcriptionally inactivated syncytins in HeLa cells. qRT-PCR analysis of non-spliced ERVWE1 and ERVFRDE1 mRNAs and respective env mRNAs detected efficient splicing of endogenously expressed RNAs in trophoblastic but not in non-placental cells. Pointing to the pathogenic potential of aberrantly expressed syncytin-1, we have found deregulation of transcription and splicing of the ERVWE1 in biopsies of testicular seminomas. Finally, ectopic expression experiments suggest the importance of proper chromatin context for the ERVWE1 splicing. Our results thus demonstrate that cell-specific retroviral splicing represents an additional epigenetic level controling the expression of endogenous retroviruses.

Transperitoneal Laparoscopic and Robotic Partial Nephrectomy for Renal Cancer in Patients with Previous Abdominal Surgery: a Single Centre Experience.

Patients with previous abdominal surgery are at an increased risk of peritoneal adhesions, which may complicate transperitoneal surgery. The objective of this article is to report single centre experience with transperitoneal laparoscopic and robotic partial nephrectomy for renal cancer in patients with previous abdominal surgery. We evaluated data from 128 patients who underwent laparoscopic or robotic partial nephrectomy from January 2010 to May 2020. Patients were divided into three groups according to the localization of main previous surgery: in the upper contralateral abdominal quadrant, in the upper ipsilateral abdominal quadrant or in the middle line, in lower abdominal quadrants. Each group was divided into two subgroups (laparoscopic/robotic partial nephrectomy). We separately analysed data of indocyanine green-enhanced robotic partial nephrectomy. Our study did not find significant difference in the rate of intraoperative or postoperative complications between any of the groups. The type of partial nephrectomy (robotic or laparoscopic) affected the surgery time, blood loss, and length of stay in hospital, but did not significantly influence the frequency of complications. Partial nephrectomy in group of patients with prior renal surgery led to a higher rate of intraoperative low-grade complications. We did not observe more favourable results for indocyanine green-enhanced robotic partial nephrectomy. The location of previous abdominal surgery does not influence the rate of intraoperative or postoperative complications. The type of partial nephrectomy (robotic or laparoscopic) does not affect the frequency of complications.

Denosumab in men receiving androgen-deprivation therapy for prostate cancer.

BACKGROUND: Androgen-deprivation therapy is well-established for treating prostate cancer but is associated with bone loss and an increased risk of fracture. We investigated the effects of denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, on bone mineral density and fractures in men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. METHODS: In this double-blind, multicenter study, we randomly assigned patients to receive denosumab at a dose of 60 mg subcutaneously every 6 months or placebo (734 patients in each group). The primary end point was percent change in bone mineral density at the lumbar spine at 24 months. Key secondary end points included percent change in bone mineral densities at the femoral neck and total hip at 24 months and at all three sites at 36 months, as well as incidence of new vertebral fractures. RESULTS: At 24 months, bone mineral density of the lumbar spine had increased by 5.6% in the denosumab group as compared with a loss of 1.0% in the placebo group (P<0.001); significant differences between the two groups were seen at as early as 1 month and sustained through 36 months. Denosumab therapy was also associated with significant increases in bone mineral density at the total hip, femoral neck, and distal third of the radius at all time points. Patients who received denosumab had a decreased incidence of new vertebral fractures at 36 months (1.5%, vs. 3.9% with placebo) (relative risk, 0.38; 95% confidence interval, 0.19 to 0.78; P=0.006). Rates of adverse events were similar between the two groups. CONCLUSIONS: Denosumab was associated with increased bone mineral density at all sites and a reduction in the incidence of new vertebral fractures among men receiving androgen-deprivation therapy for nonmetastatic prostate cancer. (ClinicalTrials.gov number, NCT00089674.)

HPV persistence and its oncogenic role in prostate tumors.

HPV has carcinogenic effects at several anatomical sites in women and men. Whether the presence of HPV in the genitourinary tract of men is associated with a higher prostate cancer risk has been a matter of research for a long-time and the results are still not fully conclusive. Similarly, the question of the reservoir of HPV infection in men is not clearly resolved. HPV DNA presence and types were evaluated by means of polymerase chain reaction in the tissue of 146 patients with benign prostate hyperplasia and prostate cancer. HPV-specific antibodies were analyzed by enzyme-linked immunosorbent assay in the sera of all patients and 172 controls. In addition, 256 biopsies taken from non-tumorous tissues were analyzed. No statistically significant differences were observed in HPV DNA prevalence between patients with benign prostate hyperplasia (2%) and patients with prostatic cancer (2%; P = 1.000). The seropositivity rates did not differ significantly between groups of subjects except for antibodies against HPV 6 VLPs which were found more often in prostate cancer patients (adjusted P = 0.018). Similarly, no difference in the seroprevalence rates for HPV 16 E6 and/or E7 oncoproteins between groups of patients and healthy controls was detected. The overall HPV prevalence in 256 healthy tissue samples was 4%. The results indicate that HPV infection is not associated with prostate oncogenesis in men. However, they imply that multiple tissues of the male genitourinary tract may be important reservoirs for the transmission of some HPV types.

[The transrectal ultrasonography of prostate in men with congenital hypogonadism treated by long term testosterone replacement therapy]. / Transrektální sonografie prostaty u muzu s vrozeným hypogonadismem léceným dlouhodobou substitucní terapií testosteronem.

BACKGROUND: The aim of the study was to evaluate prostate transrectal ultrasonography findings in men with congenital hypogonadism treated by long term testosterone replacement therapy. METHODS: We have gradually included 31 men with congenital hypogonadism in period of 2001-2011. The average follow-up was 7.3 years (2 months - 10.8 years). We have used Sustanon® 250 i.m. every 3 weeks or Nebido® i.m. every 3 months for continual testosterone replacement therapy. We performed to all patients the transrectal ultrasonography of prostate and seminal vesicles by biplanar rectal probe every 6 months. RESULTS: During the transrectal ultrasonography we observed in 22 (71.0 %) patients changes in prostatic tissue. In case of 12 patients were diagnosed asymptomatic prostatic cysts, in 9 patients prostatolithiasis and in 5 patients changes in echogenity of prostatic tissue. In 2 patients was found simultaneous occurrence of prostatic cyst and prostolithiasis, in further 2 patients simultaneous occurrence of hyperechogenic prostatic lesion and prostatolithiasis. The above described findings were diagnosed in 5 patients in the treatment lasting from 3 to 5 years, for the other 17 men with hormone replacement therapy longer than 5 years. CONCLUSIONS: The study presents long term results of complex treatment in patients with disorders of sexual development, onset and progress of puberty. The long term treatment of these patients in interdisciplinary cooperation of endocrinologist and andrologist may significantly contribute to clarify an impact of testosterone replacement therapy on prostate development.

[HIV and male infertility disorders]. / HIV a poruchy muzske plodnosti.

This review article provides information on the impact of HIV-1 on male reproductive functions. HIV-positive patients of reproductive age with now a long-term prognosis may wish to have children. If only one partner is infected, natural conception brings the risk of virus transmission. The article reviews the reproduction possibilities for HIV-positive couples and explains the ways to reduce the risk of transmitting the virus to the healthy partner or a child. Assisted reproduction techniques, especially intrauterine insemination, in vitro fertilization and intracytoplasmic sperm injection in combination with sperm washing can successfully reduce the risk of HIV transmission. Current trends and dilemmas of infertility treatment in HIV-positive couples are discussed.

Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: a case-control study.

BACKGROUND: Infection plays a role in the pathogenesis of many human malignancies. Whether prostate cancer (PCa) - an important health issue in the aging male population in the Western world - belongs to these conditions has been a matter of research since the 1970 s. Persistent serum antibodies are a proof of present or past infection. The aim of this study was to compare serum antibodies against genitourinary infectious agents between PCa patients and controls with benign prostate hyperplasia (BPH). We hypothesized that elevated serum antibody levels or higher seroprevalence in PCa patients would suggest an association of genitourinary infection in patient history and elevated PCa risk. METHODS: A total of 434 males who had undergone open prostate surgery in a single institution were included in the study: 329 PCa patients and 105 controls with BPH. The subjects' serum samples were analysed by means of enzyme-linked immunosorbent assay, complement fixation test and indirect immunofluorescence for the presence of antibodies against common genitourinary infectious agents: human papillomavirus (HPV) 6, 11, 16, 18, 31 and 33, herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (CMV), Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Neisseria gonorrhoeae and Treponema pallidum. Antibody seroprevalence and mean serum antibody levels were compared between cases and controls. Tumour grade and stage were correlated with serological findings. RESULTS: PCa patients were more likely to harbour antibodies against Ureaplasma urealyticum (odds ratio (OR) 2.06; 95% confidence interval (CI) 1.08-4.28). Men with BPH were more often seropositive for HPV 18 and Chlamydia trachomatis (OR 0.23; 95% CI 0.09-0.61 and OR 0.45; 95% CI 0.21-0.99, respectively) and had higher mean serum CMV antibody levels than PCa patients (p = 0.0004). Among PCa patients, antibodies against HPV 6 were associated with a higher Gleason score (p = 0.0305). CONCLUSIONS: Antibody seropositivity against the analyzed pathogens with the exception of Ureaplasma does not seem to be a risk factor for PCa pathogenesis. The presence or higher levels of serum antibodies against the genitourinary pathogens studied were not consistently associated with PCa. Serostatus was not a predictor of disease stage in the studied population.

[Male fertility and cancer treatment]. / Muzská plodnost a onkologická lécba.

Approximately 15% of men with newly diagnosed cancer are younger than 55 years, and about 26% of them are younger than 20 years. However the most common cause of fertility disorders is oncological treatment itself, the oncological diseases, changes in anatomy, and primary or secondary hormonal insufficiency are also significant factors. The chemotherapy, radiation, or their combination reduce sperm count, impair sperm motility and cause disorders in morphology and DNA integrity. Prognosis of sperm production recovery depends on the type of cancer, stage of the disease, patient age, drug treatment, treatment route and dosage, and pre-treatment male fertility.

[Urologic complications of HIV infection]. / Urologické komplikace HIV/AIDS.

As life expectancy of patients infected by Human Immunodeficiency Virus (HIV) has prolonged, they are treated by physicians of different specialities. This article focuses on urologic complications of HIV infection. Urinary tract infections in HIV positive patients are more frequent than in otherwise healthy individuals and less common microorganisms can be involved. Sexually transmitted diseases are a commonplace. Certain malignancies of the genitourinary tract are more often diagnosed in HIV positive than in HIV negative population. Impairment of kidney function is usually caused by HIV-associated nephropathy. Acute renal failure can also occur. Indinavir causes urinary stones formation. Male circumcision is an effective method of HIV transmission prevention.

Robotic Partial Nephrectomy with Indocyanine Green Fluorescence Navigation.

Partial nephrectomy (PN) is a recommended type of treatment of localised renal tumors. Real-time intraoperative imaging technique, such as fluorescence imaging with indocyanine green (ICG) administration helps to improve intraoperative and postoperative outcomes in patients who underwent PN. Our work presents results of patients who underwent robotic PN with ICG navigation. A total of 37 patients underwent robotic PN with application of ICG between April 2015 and May 2019. A total amount of 5 mg of ICG was applied intravenously, and then robotic PN was performed with fluorescent imaging. ICG was used by the surgeon's decision according to unfavourable anatomical properties of tumor or to high R.E.N.A.L. nephrometry score. An exact border between perfused and nonperfused tissue was detected, and exact tumor's branch of the renal artery was clamped. Robotic PN with ICG-fluorescence imaging navigation was performed in 37 cases with a preoperative average diameter of tumor of 31 mm. The mean surgery time was 133 minutes, and the mean estimated blood loss was 190 mL. Arterial clamping was performed in 35 cases. The mean duration of warm ischemia was 14 minutes. Application of ICG enabled specific tumor-supplying vessel clamping in 25 cases. Two complications of grade II according to the Clavien-Dindo classification occurred intraoperatively, and one complication of grade III was observed. Renal function changes showed favourable results for the cases with superselective clamping. Finally, an administration of ICG eases superselective clamping of tumor-specific branch of renal artery and helps to preserve normal renal function with acceptable oncological results.

Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancer.

AIM: The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D-PDS) for diagnostics of extraprostatic extension of prostate cancer. PATIENTS AND METHODS: In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D-PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis. RESULTS: The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D-PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D-PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D-PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension. CONCLUSION: Our data suggest that the 3D-PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension.

Tissue and serum levels of principal androgens in benign prostatic hyperplasia and prostate cancer.

Androgens are considered to play a substantial role in pathogenesis of both benign prostatic hyperplasia (BPH) and prostate cancer. The importance of determination of androgen levels in tissue and serum for cancer progression and prognosis has been poorly understood. The aim of study was to find out hormonal differences in both diseases, their correlations between intraprostatic and serum levels and predicted value of their investigation. Testosterone, dihydrotestosterone, androstenedione and also epitestosterone were determined in prostate tissue from 57 patients who underwent transvesical prostatectomy for BPH and 121 patients after radical prostatectomy for prostate cancer. In 75 subjects with cancer and 51 with BPH the serum samples were analyzed for testosterone, dihydrotestosterone and SHBG. Significantly higher intraprostatic androgen concentrations, i.e. 8.85+/-6.77 versus 6.44+/-6.43 pmol/g, p<0.01 for dihydrotestosterone, and 4.61+/-7.02 versus 3.44+/-4.53 pmol/g, p<0.05 for testosterone, respectively, were found in patients with prostate cancer than in BPH. Higher levels in cancer tissue were found also for epitestosterone. However, no differences were found in serum levels. Highly significant correlations occurred between all pairs of intraprostatic androgens and also epitestosterone as well as between serum testosterone and dihydrotestosterone (p<0.001) in both BPH and cancer groups. Correlation was not found between corresponding tissue and serum testosterone and dihydrotestosterone, either in benign or cancer samples. The results point to importance of intraprostatic hormone levels for evaluation of androgen status of patients, contrasting to a low value of serum hormone measurement.

The endocrine profiles in men with localized and locally advanced prostate cancer treated with radical prostatectomy.

OBJECTIVE: Prostate cancer is now recognized as one of the principal medical problems facing male population and the commonest cancer in males in delevoped countries. The aim of this study was to find out whether serum hormone levels differ significantly in localized (pT2) and locally advanced (pT3-pT4 or N1) prostate cancer. METHODS: In 250 men (mean age+/-SEM: 63.8+/-0.4) who underwent radical retropubic prostatectomy for histologically confirmed prostate cancer were analyzed serum samples for total testosterone, dehydroepiandrosterone sulfate, estradiol, progesterone, prolactin, cortisol, sex hormone-binding globulin, luteinizing hormone and follicle stimulating hormone. Free testosterone content was calculated from total testosterone and SHBG concentrations. RESULTS: Significantly lower serum level of FSH, i.e. 5.63+/-0.31 vs. 7.07+/-0.65 U/L was found in patients with localized prostate cancer than in locally advanced (p<0.05). Significant correlation was found between serum levels of DHEAS and cortisol in both groups (p<0.02), estradiol and prolactin in patients with locally advanced prostate cancer, as well between LH and prolactin (p<0.05). No differences were found in other observed hormones. CONCLUSION: The results point to importance of hormone status as possible additional prognostic marker for patients with prostate cancer. Considerable research is needed to further understand influence of hormones on prostate cancer.

Determination of selected bisphenols, parabens and estrogens in human plasma using LC-MS/MS.

In this study, a novel liquid chromatography - tandem mass spectrometry method for the simultaneous determination of bisphenols (BPA, BPS, BPF, BPAF), parabens (methyl-, ethyl-, propyl-, butyl-, benzyl-paraben) and estrogens (estrone, estradiol, estriol) in human plasma is presented. Since all analytes possess the phenolic group, dansyl chloride derivatization was applied in order to gain high sensitivity. The method was validated according to FDA guidelines, and all validation requirements were satisfactory. The lower limits of quantifications were 41.6, 54.9, 43.5 and 150.8pg/mL for BPA, BPS, BPF and BPAF; 172, 149, 171, 134 and 202pg/mL for methyl-, ethyl-, propyl-, butyl- and benzyl-paraben; 10.5, 6.7 and 9.4pg/mL for estrone, estradiol and estriol, respectively. This is the first method allowing the determination of plasma bisphenols, parabens and estrogens in one run, and also the first determination of BPF levels in human plasma. The method was used to examine the plasma levels of healthy normospermic men, where three times higher plasma levels of BPF than BPA were found.

Endocrine disruptors and other inhibitors of 11ß-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition.

Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11ß-hydroxysteroid dehydrogenase (11ßHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11ßHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11ßHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11ßHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.

Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic.

BACKGROUND: In the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. OBJECTIVES: To shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. METHODS: We determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. RESULTS: Seminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=-0.198; p=0.009), sperm count (r=-0.178; p=0.018) and morphology (r=-0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. CONCLUSION: BPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality.

A rare Robertsonian translocation rob(14;22) carrier with azoospermia, meiotic defects, and testicular sperm aneuploidy.

Male infertility is a serious problem in an increasing number of couples. We report an infertile man with non-obstructive azoospermia and karyotype 45,XY,rob(14;22). The immunofluorescence analysis of his testicular tissue using antibodies to SYCP1, SYCP3, HORMAD2, MLH1, and centromeres showed delayed synapsis of the chromosomes involved in the translocation, a varying extent of trivalent asynapsis and its association with sex chromosomes. The mean frequency of meiotic recombination per cell was within the range of normal values. Fluorescence in situ hybridization (FISH) with probes for chromosomes 14 and 22 revealed 5.83% of chromosomally abnormal testicular spermatozoa. FISH with probes for chromosomes X, Y, and 21 showed frequencies of disomic and diploid testicular spermatozoa increased when compared to ejaculated sperm of healthy donors, but comparable with published results for azoospermic patients. PGD by FISH for the translocation and aneuploidy of chromosomes X, Y, 13, 18, and 21 showed a normal chromosomal complement in one out of three analyzed embryos. A healthy carrier girl was born after the embryo transfer. This study shows the benefits of preimplantation genetic diagnosis in a case of a rare Robertsonian translocation carrier with azoospermia and a relatively low frequency of chromosomally unbalanced testicular spermatozoa.