Synbiotic (FamiLact) administration in idiopathic male infertility enhances sperm quality, DNA integrity, and chromatin status: A triple-blinded randomized clinical trial

Background: Idiopathic male infertility is often treated empirically. A recent body of evidence has indicated the association between pro ± prebiotics administration and improvement in semen parameters. Objective: To assess the effect of FamiLact (probiotic + prebiotic) administration on male subjects with idiopathic infertility. Materials and Methods: Fifty-six men with idiopathic male infertility were randomly/equally divided into two groups. Men in the case and control groups received 500 mg of FamiLact and an identical placebo for 80 days, respectively. A semen sample was obtained from each of the participants before initiation and after the termination of the treatment course. Samples underwent regular semen analysis and were further analyzed to assess the level of DNA damage (sperm chromatin structure assay), oxidative stress (BODIPY C11 staining), and protamine deficiency (chromomycin-A3 staining) in spermatozoa. Results: No significant difference was observed between the baseline values of both groups. After intervention, mean sperm concentration, motility, and normal morphology were significantly higher in the FamiLact group compared to the placebo group (p < 0.05). In the FamiLact receivers, we detected improvement regarding the following parameters: concentration, motility, abnormal morphology, sperm lipid peroxidation, and DNA fragmentation (p ≤ 0.02). Likewise, in the placebo group, we noticed a decrease in the post-medication mean value of DNA fragmentation (p = 0.03) while observing no significant difference regarding other parameters. Conclusion: FamiLact administration improves sperm concentration, motility, and abnormal morphology and decrease sperm DNA damage, possibly through alleviating oxidative stress in the seminal fluid. Key words: Male infertility, DNA fragmentation, Sperm, Synbiotics, Probiotics, Fertility agents.

The Effect of lead exposure of mice during pregnancy on the morphology of epididymal and testicular spermatozoa of their offspring

Introduction: The aims of this study were to assess the differences in the percentages of abnormal morphology between the epididymal and testicular spermatozoa of mature male offspring mice whose mothers were injected with various doses of lead acetate during gestation. Materials and Methods: Seventy two healthy female mice were divided into three major groups according to the number of injections involving 1, 2 or 3 injections at 8th day; 8th and 13th days; and 8th, 13th and 18th days of gestation period, respectively. Each major group was subdivided into four minor groups according to the dosage of lead administered (0, 25, 50 and 100) mg/Kg. Results: The percentages of abnormal morphology of epididymal and testicular spermatozoa were studied and the data were statistically analyzed. The results of this study proved that an increased number of injections and/or dose of lead acetate injected to the mothers during gestation cause an elevation in the percentage of abnormal morphology of both epididymal and testicular spermatozoa of the male mice offspring. Conclusion: In conclusion this study demonstrated that lead acetate when exposed prenatally have toxic effects on the sperm in the offspring male mice resulting in abnormal morphology of spermatozoa. The most likely causative factor is disturbances in the phase(s) of spermatogenesis and/or spermiogenesis.

Abstract 17250: Quantitative T Wave Morphology Analysis in Rett Syndrome Patients

Introduction: Rett syndrome (RTT) is a genetic neurologic disorder associated with a high incidence of sudden death. Abnormal cardiac repolarization is a potential risk factor for sudden death in this population. RTT patients may have prolonged corrected QT (QTc) on electrocardiogram (ECG) that is a sensitive marker of torsades des pointes. However, other repolarization markers such as T wave morphology, the time it takes the T wave to return to baseline from peak amplitude (Tpeak - Tend), and heart rate corrected JTpeak have not been studied. Hypothesis: Rett syndrome patients have abnormal cardiac repolarization. Methods: Retrospective T wave analysis was performed using QT Guard software. T wave morphology and heterogeneity parameters of RTT patients were compared to ECGs of age and sex matched healthy controls. A composite T wave morphology score was calculated from individual feature of flatness, notching, and asymmetry; a higher score means more abnormal morphology. Heterogeneity of repolarization was represented by the principal component analysis ratio 2 (PCA-2). Results: 57 Rett patients (260 ECG) and 121 controls (134 ECG) were studied. The RTT group had longer QTc (p = 0.001) along with more abnormal T-wave morphology scores and heterogeneity parameters when compared to controls (Tables 1, 2). RTT patients without long QTc also had more abnormal morphology scores than controls (p = 0.001). Conclusion: Cardiac repolarization is diffusely abnormal in RTT even in the absence of long QTc. T wave morphology analysis may be used to detect and monitor abnormal cardiac repolarization in RTT in clinical practice.

(D620N) VPS35 causes the impairment of Wnt/β-catenin signaling cascade and mitochondrial dysfunction in a PARK17 knockin mouse model

Patients with familial type 17 of Parkinson’s disease (PARK17) manifest autosomal dominant pattern and late-onset parkinsonian syndromes. Heterozygous (D620N) mutation of vacuolar protein sorting 35 (VPS35) is genetic cause of PARK17. We prepared heterozygous VPS35D620N/+ knockin mouse, which is an ideal animal model of (D620N) VPS35-induced autosomal dominant PARK17. Late-onset loss of substantia nigra pars compacta (SNpc) dopaminergic (DAergic) neurons and motor deficits of Parkinson’s disease were found in 16-month-old VPS35D620N/+ mice. Normal function of VPS35-containing retromer is needed for activity of Wnt/β-catenin cascade, which participates in protection and survival of SNpc DAergic neurons. It was hypothesized that (D620N) VPS35 mutation causes the malfunction of VPS35 and resulting impaired activity of Wnt/β-catenin pathway. Protein levels of Wnt1 and nuclear β-catenin were reduced in SN of 16-month-old VPS35D620N/+ knockin mice. Downregulated protein expression of survivin, which is a target gene of nuclear β-catenin, and upregulated protein levels of active caspase-8 and active caspase-9 were observed in SN of VPS35D620N/+ mice at age of 16 months. VPS35 is involved in controlling morphology and function of mitochondria. Impaired function of VPS35 caused by (D620N) mutation could lead to abnormal morphology and malfunction of mitochondria. A significant decrease in mitochondrial size and resulting mitochondrial fragmentation was found in tyrosine hydroxylase-positive and neuromelanin-positive SNpc DAergic neurons of 16-month-old VPS35D620N/+ mice. Mitochondrial complex I activity or complex IV activity was reduced in SN of 16-month-old VPS35D620N/+ mice. Increased level of mitochondrial ROS and oxidative stress were found in SN of 16-month-old VPS35D620N/+ mice. Levels of cytosolic cytochrome c and active caspase-3 were increased in SN of VPS35D620N/+ mice aged 16 months. Our results suggest that PARK17 mutant (D620N) VPS35 impairs activity of Wnt/β-catenin signaling pathway and causes abnormal morphology and dysfunction of mitochondria, which could lead to neurodegeneration of SNpc DAergic cells.

Effect of trans-resveratrol or ubiquinol supplementation on the sperm morphology of CD-1 mice subjected to forced swimming

This study was undertaken to assess the effect of a three-minute forced swimming protocol for 50 days, with and without antioxidant administration on sperm morphology in CD-1 mice. Seventy-five mice were randomly allocated to one of the following five groups: no exercise (control group; CG), swimming without antioxidant administration (EX), swimming with trans-resveratrol administration (EX-Resv), swimming with ubiquinol and excipient administration (Kaneka´s ubiquinol) (EX-Ubiq), and swimming with just only the excipient for Kaneka´s ubiquinol administration (EX-Excp). The EX group showed that 53.03±4.83% of sperm had abnormal morphology, with significant differences with regards to CG (46.47±10.57%) (p<0.05). The number of sperm with abnormal morphology decreased in all groups treated with either antioxidants or with excipient; this was most noticeable in EX-Ubiq (p<0.05). The percentage of midpiece and tail, as well as multiple anomalies were greater in EX than in CG (p<0.05). While both antioxidants, as well as the excipient, decreased midpiece and head anomalies, only trans-resveratrol and ubiquinol had an effect on multiple anomalies. Furthermore, only trans-resveratrol had an effect upon tail anomalies. The imposed exercise caused alterations in CD-1 mice sperm morphology, and antioxidant treatment seems suitable to decrease morphological anomalies. Both trans- resveratrol and ubiquinol were effective in decreasing simple as well as multiple sperm anomalies.

Description of a new species of Paratullbergia (Collembola, Tullbergiidae) from China with the report of an abnormal antenna

A new species of Tullbergiidae, Paratullbergia chuana sp. nov. from Sichuan Province, southwest China is described. Paratullbergia chuana is characterised by the presence of one pair of pseudocelli on each segment from Th. I–Abd. V and a formula of 11/111/11111, postantennal organ composed by 34–50 vesicles arranged in two rows, seta px present on Abd. IV, setae a2 and a4 on Abd. V as macrosetae, p4 as mesoseta, and a less differentiated sensillum p3 on Abd. V. In addition, chaetotaxic variations on Abd. IV and V are discussed. An abnormal morphology of an antenna that was observed for the first time is reported.