Zika-Induced Male Infertility in Mice Is Potentially Reversible and Preventable by Deoxyribonucleic Acid Immunization.

Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice. Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J. Results: Although all mice challenged with ZIKV developed viremia, most of them were asymptomatic, showed no weight loss, and survived infection. On day 28 postinfection, none of the unvaccinated, infected mice (9 of 9) exhibited abnormal spermatozoa counts or motility. However, 33% (3 of 9) and 36% (4 of 11) of mated males from this group were infertile, from 2 independent studies. Contrarily, males from the noninfected and the vaccinated, infected groups were all fertile. On days 75 and 207 postinfection, partial recovery of fertility was observed in 66% (2 of 3) of the previously infertile males. Conclusions: This study reports the effects of ZIKV infection on male fertility in a sublethal, immunodeficient mouse model and the efficacy of GLS-5700 vaccination in preventing male infertility.

Daylily protein constituents of the pollen and stigma a proteomics approach.

This study was aimed at the identification and quantification of the protein components of the pollen grains in parallel with the distal stigmatic tissue of tetraploid cultivars. Proteomes were analyzed using iTRAQ 4plex labeling, peptides separation by online RP-nano-LC and analysis by ESI-MS/MS. Protein identification and quantification were made using the Asparagales database as a reference. A total of 524,037 MS/MS spectra were produced from pollen and stigma samples. From these, a total of 8368 peptides wereidentified corresponding to 994 unique peptides and 432 protein groups. Among them, 128 differentially expressed proteins were retained for further analysis. In absence of the daylily genome availability, we exploited numerous databases and bioinformatics resources to exploring the putative biological functions of these proteins. The profile of differentially expressed proteins suggests an important representation of functions associated to the signalling and response against endogenous and environmental stresses, including several enzymes implicated in the biosynthesis of antibiotics. The abundance in stigma of several structural proteins of the ribosomal sub-units as well as of the core histones suggest that the translation processes and the regulation of gene expression in stigma is a more active mechanism than in pollen. In addition, pollen prioritizes the synthesis of fructose and glucose as opposed to sucrose in stigma as a source of energy. Finally, the modulated proteins in Hemerocallis point to several pathways that give potential clues concerning the molecular mechanisms underlying the functions of the pollen and the stigmatic fluid in daylily reproduction.

Cysteine-rich secretory protein 1 in seminal plasma: potential biomarker for the distinction between obstructive and nonobstructive azoospermia.

OBJECTIVE: To investigate the presence of cysteine-rich secretory protein 1 (CRISP1) in seminal plasma as a means of distinguishing between obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). DESIGN: Seminal plasma from normospermic donors (n = 45) and azoospermic donors (n = 80) was examined to determine CRISP1 levels. Neutral alpha-glucosidase (NAG) enzymatic activity was measured for comparison with CRISP1 levels. SETTING: Research unit of an academic medical center. PATIENT(S): Normospermic and azoospermic donors from the clinical andrology laboratory of the centre hospitalier universitaire de Québec and from Mount Sinai Hospital. INTERVENTION(S): Seminal CRISP1 measurement by Western blot analysis. Neutral alpha-glucosidase activity was evaluated by a photometric method. MAIN OUTCOME MEASURE(S): Seminal plasma CRISP1 levels, NAG activity, cutoff value, sensitivity, and specificity. RESULT(S): All seminal plasma samples from normospermic and nonobstructive azoospermic donors were CRISP1 positive, whereas CRISP1 was absent or present at low levels in samples from patients with OA. A significant correlation between seminal CRISP1 levels and NAG activity was found in azoospermic semen samples. The cutoff point to distinguish between donors with NOA or OA was established at 0.655 (relative intensity). At this threshold, specificity was 85% and sensitivity was 92%. CONCLUSION(S): Seminal CRISP1 combined with NAG activity can potentially distinguish between OA and NOA.

Early detection of prostate cancer local recurrence by urinary prostate-specific antigen.

PURPOSE: We assessed the role of urinary prostate-specific antigen (uPSA) in the follow-up of prostate cancer after retropubic radical prostatectomy (RRP) for the early detection of local recurrences. METHODS: We recruited 50 patients previously treated for prostate cancer with RRP and who had not experienced a prostate-specific antigen (PSA) recurrence within their first postoperative year into a cross-sectional laboratory assessment and prospective 6-year longitudinal follow-up study. We defined biochemical failure as a serum PSA (sPSA) of 0.3 µg/L or greater. Patients provided blood samples and a 50-mL sample of first-voided urine. We performed Wilcoxon rank-sum and Fisher exact tests for statistical analysis. RESULTS: The median sPSA was 0.13 µg/L. The median uPSA was 0.8 µg/L, and was not significantly different when comparing Gleason scores or pathological stages. Of the 50 patients, 27 initially had a nondetectable sPSA but a detectable uPSA, and 11 patients experienced sPSA failure after 6 years. Six patients had detectable sPSA and uPSA initially. Fifteen patients were negative for both sPSA and uPSA, and 13 remained sPSA-free after 6 years. The odds ratio (OR) of having sPSA failure given a positive uPSA test was 4.5 if sPSA was undetectable, but was reduced to 2.6 if sPSA was detectable. The pooled Mantel-Haenszel OR of 4.2 suggested that a detectable uPSA quadrupled the risk of recurrence, independent of whether sPSA was elevated or not. The sensitivity of uPSA for detecting future sPSA recurrences was 81% and specificity was 45%. CONCLUSION: Urinary PSA could contribute to an early detection of local recurrences of prostate cancer after a radical prostatectomy.

Urinary PSA: a potential useful marker when serum PSA is between 2.5 ng/mL and 10 ng/mL.

INTRODUCTION: Our objective was to evaluate the usefulness of urinary prostate specific antigen (PSA) in the differential diagnosis of benign prostatic hyperplasia (BPH) and prostate cancer. METHODS: We undertook a prospective study and obtained informed consent from 170 men. They provided blood samples to measure serum PSA and 50 mL of first-voided urine to measure urinary PSA. Seventy-seven men were diagnosed with BPH; 42 patients had newly diagnosed prostate cancer; and 51 were selected as age-matched control subjects. Data were analyzed using Wilcoxon signed rank tests, receiver operating characteristic (ROC) curves and logistic regression. RESULTS: Prostate volume was 35 cm(3) and 45 cm(3) (p < 0.05), serum PSA was 9.7 ng/mL and 4.5 ng/mL (p < 0.001) and PSA density was 0.28 and 0.11 (p < 0.01) for prostate cancer and BPH patients, respectively. Overall, urinary PSA was not significantly different, but PSA ratio (urinary:serum) was significantly different at 6.7 and 30.6 (p < 0.001) for prostate cancer and BPH patients, respectively. A subgroup with serum PSA between 2.5 ng/mL and 10.0 ng/mL was selected and urinary PSA was significant: 52.6 ng/mL (n = 29) and 123.2 ng/mL (n = 35) (p < 0.05) for prostate cancer and BPH patients, respectively. PSA ratios were also significant (p = 0.007). ROC curves identified a cutoff for urinary PSA at > 150 ng/mL, with a sensitivity of 92.5%. When comparing prostate cancer patients with age-matched control subjects, serum PSA, urinary PSA and PSA ratio were different (p = 0.004). CONCLUSION: Our study supports urinary PSA as a useful marker in the differential diagnosis of prostate cancer and BPH, especially when serum PSA is between 2.5 ng/mL and 10 ng/mL. Low urinary PSA and PSA ratios point toward prostate cancer. A urinary PSA threshold of > 150 ng/mL may be used to decrease the number of prostatic biopsies.

Can we get away from serum total testosterone in the diagnosis of andropause?

Because of its multifactorial origin, andropause is usually considered as a clinical entity whose diagnosis is difficult. Practitioners sometimes distrust the symptoms and the diagnostic tools. The clinical manifestations are however the reflection of a lack of anabolism commonly associated with a decreased production of testosterone which is translated in decreased serum values of total testosterone, bioavailable testosterone and calculated values of testosterone. Because of the similarity between the age of the control group and of andropausal men in this study, the Sex Hormone Binding Globulin dogma postulating a modest increase of the glycoprotein with age is evacuated from the argument and therefore it is proposed to rely on total testosterone as a first line assay to support the diagnosis of andropause; however the presence of confounding factors to the diagnosis sometimes require an easy access to calculated values of free or bioavailable testosterone.

Catabolic/anabolic balance and muscle wasting in patients with COPD.

BACKGROUND: The mechanisms leading to muscle wasting in patients with COPD are still uncertain. This study was undertaken to evaluate the relationships among circulating levels of catabolic factors (ie, interleukin [IL]-6 and cortisol), anabolic factors (ie, bioavailable testosterone [Tbio], dehydroepiandrosterone sulfate [DHEAS], and insulin-like growth factor [IGF]-I), and mid-thigh muscle cross-sectional area (MTCSA) in patients with COPD. METHODS: Serum levels of the above factors were measured in 45 men with COPD (mean [+/- SEM] FEV(1), 43 +/- 3% predicted; mean age, 67 +/- 1 years) and 16 sedentary healthy men of similar age. MTCSA was quantified using CT scanning. Patients with COPD were subdivided into two groups according to the MTCSA (< 70 or >or= 70 cm(2)). RESULTS: There was a greater prevalence of hypogonadism (ie, Tbio, < 2 nmol/L) in patients with COPD compared to control subjects (22% vs 0%, respectively). Patients with an MTCSA of < 70 cm(2) had significantly reduced levels of DHEAS compared to those in healthy subjects (p < 0.01). IL-6 levels were significantly higher in both subgroups of COPD patients compared to those in control subjects (p < 0.005). The cortisol/DHEAS, IL-6/DHEAS, IL-6/Tbio, and IL-6/IGF-I ratios were significantly greater in COPD patients with an MTCSA of < 70 cm(2) compared to those in control subjects (p < 0.05). The cortisol/DHEAS and IL-6/DHEAS ratios were also significantly greater in COPD patients with an MTCSA of < 70 cm(2) than in COPD patients with an MTCSA of >or= 70 cm(2) (p < 0.05). In a stepwise multiple regression analysis, the IL-6/DHEAS ratio explained 20% of the variance in MTCSA (p < 0.005). CONCLUSION: Catabolic/anabolic disturbances were found in COPD patients leading to a shift toward catabolism and possibly to the development of peripheral muscle wasting.

Thermoreversible gel formulation containing sodium lauryl sulfate as a potential contraceptive device.

The contraceptive properties of a gel formulation containing sodium lauryl sulfate were investigated in both in vitro and in vivo models. Results showed that sodium lauryl sulfate inhibited, in a concentration-dependent manner, the activity of sheep testicular hyaluronidase. Sodium lauryl sulfate also completely inhibited human sperm motility as evaluated by the 30-sec Sander-Cramer test. The acid-buffering capacity of gel formulations containing sodium lauryl sulfate increased with the molarity of the citrate buffers used for their preparations. Furthermore, experiments in which semen was mixed with undiluted gel formulations in different proportions confirmed their physiologically relevant buffering capacity. Intravaginal application of the gel formulation containing sodium lauryl sulfate to rabbits before their artificial insemination with freshly ejaculated semen completely prevented egg fertilization. The gel formulation containing sodium lauryl sulfate was fully compatible with nonlubricated latex condoms. Taken together, these results suggest that the gel formulation containing sodium lauryl sulfate could represent a potential candidate for use as a topical vaginal spermicidal formulation to provide fertility control in women.