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Diagnostics (Basel, Switzerland) Mar 2024(1) Background: Standard semen analysis methods may exhibit variability between observers and/or human error; therefore, additional methods are needed to overcome these...
Introducing a New Smartphone Applied Semen Analyzer, SpermCell™: A Cross-Sectional Validation Study with a Comparative Analysis and a Mini Patient Questionnaire on a Large Sample Cohort.
(1) Background: Standard semen analysis methods may exhibit variability between observers and/or human error; therefore, additional methods are needed to overcome these handicaps. We aimed to present a new smartphone-applied semen analyzer, Sperm Cell™, investigate its diagnostic efficacy by comparing it with the standard analysis method, and determine its user-friendly nature. (2) Methods: A cross-sectional study was conducted on a large sample cohort, including 102 men. Three semen analyses were performed for each semen sample. The first employed the standard manual method, whereas the others were smartphone-based analyses performed by technicians and patients. We compared major semen parameters between the three semen analyses. The user-friendly nature of the analyzer was also evaluated with a mini-questionnaire completed by the participants. (3) Results: The determined median sperm count, motile sperm count, and percentage of motile sperms, on standard manual semen analysis, were 50.00 × 10/mL (0-160 × 10/mL), 23.94 × 10/mL (0-108 × 10/mL) and 50.00% (0-73.00%), respectively. Median sperm count and motile sperm count were 50.52 × 10/mL (<1-150 × 10/mL) vs. 55.77 × 10/mL (<1-160 × 10/mL) and 23.34 × 10/mL (0-105 × 10/mL) vs. 23.53 × 10/mL (0-104 × 10/mL) for SpermCell™-based semen analysis performed by a technician and patients themselves, respectively. The percentages of motile sperms were 47.40% (0-67.00%) vs. 47.61% (0-80.20%), respectively. All the parameters were statistically similar between the three semen analysis methods ( > 0.05 for each). The SpermCell™ analysis results were correlated with the standard manual method with up to 0.85 correlation coefficients. Moreover, substantial diagnostic accuracy, sensitivity and specificity were obtained in determining the oligospermia and asthenozoospermia via the device-based analyses performed by technician and patients. The mini-questionnaire results revealed that the analyzer is useful. (4) Conclusions: The novel smartphone-applied semen analyzer is a helpful tool with acceptable diagnostic accuracy in determining the major semen parameters. It can be used as an efficient at-home point-of-care testing method in the initial assessment of couples with infertility concerns.
PubMed: 38611602
DOI: 10.3390/diagnostics14070689 -
Journal of Cellular and Molecular... Apr 2024Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important...
Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.
Topics: Animals; Humans; Male; Mice; Asthenozoospermia; Infertility, Male; Mice, Knockout; Mutation; Oligospermia; Semen; Sperm Motility; Spermatozoa; Membrane Proteins
PubMed: 38509755
DOI: 10.1111/jcmm.18215 -
American Journal of Men's Health 2024Seasonal changes are assumed to affect various sperm characteristics based on photoperiods, temperature, and air pollution. According to the literature, most studies... (Review)
Review
Impact of Season Variation on Semen Quality: A Comprehensive Retrospective Analysis of Data From Patients at an Eastern Iranian Tertiary Care Fertility Center Over a Decade.
Seasonal changes are assumed to affect various sperm characteristics based on photoperiods, temperature, and air pollution. According to the literature, most studies were performed on populations of Western countries, and there are limited studies performed in the Middle East with variable results. This study evaluated the seasonality of sperm characteristics among men of reproductive age in an andrology center in Kerman, Iran, where the seasonal temperature varies significantly, with average temperatures ranging from 50 °F (10 °C) to 75.2 °F (24 °C). We retrospectively evaluated the sperm analysis test record. Sperm samples were obtained from 2,948 men during 10 years, excluding those with azoospermia. Samples were assessed for volume, concentration, motility, and morphology according to the World Health Organization (WHO) criteria. We performed a comprehensive comparative literature review of the studies investigating the association between seasonal variation and sperm quality. The mean semen volume was higher in the summer compared with other seasons ( = .04). The mean percentage of sperm motility was higher in the spring and less in winter ( = .03). Sperm morphology-related parameters, measured by the percent of normal morphology, were significantly better in winter ( = .03). Our findings suggest seasonality of sperm characteristics among men of fertility age. Semen volume, motility, and morphology were affected by the photoperiod of reproductive seasons. Results might support the influential role of seasonal variations in the possibility of fertility, especially among those using assisted reproductive technologies and those with oligospermia.
Topics: Humans; Male; Semen Analysis; Seasons; Retrospective Studies; Iran; Semen; Sperm Count; Tertiary Healthcare; Sperm Motility
PubMed: 38509696
DOI: 10.1177/15579883241237505 -
Cureus Feb 2024We presented a 30-year-old man suffering from severe oligozoospermia caused by substantial sperm maturation arrest around the spermatid stage. Additionally, he was...
We presented a 30-year-old man suffering from severe oligozoospermia caused by substantial sperm maturation arrest around the spermatid stage. Additionally, he was suffering from a varicocele. For three years, the couple had been trying to conceive. The clinical and endocrinological evaluation of the woman revealed that she was medically fit to undergo pregnancy. We performed laparoscopic ligation of the spermatic vein to treat the varicocele. Semen analysis was conducted at the beginning of the clinical pregnancy journey and after three and six months of treatment, which included 80 mg/day of phytoestrogens for six months. Six months following the end of the therapy, a second semen analysis was carried out. The inherent characteristics of the semen substantially improved in the third month, facilitating the implementation of the reproductive method referred to as intrauterine insemination. Following this treatment, the patient delivered a healthy baby weighing 3300 g. Sperm parameters improved substantially after three months of therapy; however, they reverted to baseline values during the wash-out period. These promising findings strongly suggest that phytoestrogens could be utilized for therapeutic purposes in the management of oligozoospermia. To further demonstrate the potential impact of phytoestrogens on male infertility, it is imperative to conduct a validation phase and randomized controlled trials.
PubMed: 38481882
DOI: 10.7759/cureus.54071 -
Human Reproduction (Oxford, England) May 2024Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies?
STUDY QUESTION
Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies?
SUMMARY ANSWER
We reveal two distinct subgroups of cryptozoospermic (Crypto) patients based on testicular tissue composition, testicular volume, and FSH levels.
WHAT IS KNOWN ALREADY
Cryptozoospermic patients present with a sperm concentration below 0.1 million/ml. While the etiology of the severely impaired spermatogenesis remains largely unknown, alterations of the spermatogonial compartment have been reported including a reduction of the reserve stem cells in these patients.
STUDY DESIGN, SIZE, DURATION
To assess whether there are distinct subgroups among cryptozoospermic patients, we applied the statistical method of cluster analysis. For this, we retrospectively selected 132 cryptozoospermic patients from a clinical database who underwent a testicular biopsy in the frame of fertility treatment at a university hospital. As controls (Control), we selected 160 patients with obstructive azoospermia and full spermatogenesis. All 292 patients underwent routine evaluation for endocrine, semen, and histological parameters (i.e. the percentage of tubules with elongated spermatids). Moreover, outcome of medically assisted reproduction (MAR) was assessed for cryptozoospermic (n = 73) and Control patients (n = 87), respectively. For in-depth immunohistochemical and histomorphometrical analyses, representative tissue samples from cryptozoospermic (n = 27) and Control patients (n = 12) were selected based on cluster analysis results and histological parameters.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This study included two parts: firstly using clinical parameters of the entire cohort of 292 patients, we performed principal component analysis (PCA) followed by hierarchical clustering on principal components (i.e. considering hormonal values, ejaculate parameters, and histological information). Secondly, for histological analyses seminiferous tubules were categorized according to the most advanced germ cell type present in sections stained with Periodic acid Schif. On the selected cohort of 39 patients (12 Control, 27 cryptozoospermic), we performed immunohistochemistry for spermatogonial markers melanoma-associated antigen 4 (MAGEA4) and piwi like RNA-mediated gene silencing 4 (PIWIL4) followed by quantitative analyses. Moreover, the morphologically defined Adark spermatogonia, which are considered to be the reserve stem cells, were quantified.
MAIN RESULTS AND THE ROLE OF CHANCE
The PCA and hierarchical clustering revealed three different clusters, one of them containing all Control samples. The main factors driving the sorting of patients to the clusters were the percentage of tubules with elongated spermatids (Cluster 1, all Control patients and two cryptozoospermic patients), the percentage of tubules with spermatocytes (Cluster 2, cryptozoospermic patients), and tubules showing a Sertoli cells only phenotype (Cluster 3, cryptozoospermic patients). Importantly, the percentage of tubules containing elongated spermatids was comparable between Clusters 2 and 3. Additional differences were higher FSH levels (P < 0.001) and lower testicular volumes (P < 0.001) in Cluster 3 compared to Cluster 2. In the spermatogonial compartment of both cryptozoospermic Clusters, we found lower numbers of MAGEA4+ and Adark spermatogonia but higher proportions of PIWIL4+ spermatogonia, which were significantly correlated with a lower percentage of tubules containing elongated spermatids. In line with this common alteration, the outcome of MAR was comparable between Controls as well as both cryptozoospermic Clusters.
LIMITATIONS, REASONS FOR CAUTION
While we have uncovered the existence of subgroups within the cohort of cryptozoospermic patients, comprehensive genetic analyses remain to be performed to unravel potentially distinct etiologies.
WIDER IMPLICATIONS OF THE FINDINGS
The novel insight that cryptozoospermic patients can be divided into two subgroups will facilitate the strategic search for underlying genetic etiologies. Moreover, the shared alterations of the spermatogonial stem cell compartment between the two cryptozoospermic subgroups could represent a general response mechanism to the reduced output of sperm, which may be associated with a progressive phenotype. This study therefore offers novel approaches towards the understanding of the etiology underlying the reduced sperm formation in cryptozoospermic patients.
STUDY FUNDING/COMPETING INTEREST(S)
German research foundation CRU 326 (grants to: SDP, NN). Moreover, we thank the Faculty of Medicine of the University of Münster for the financial support of Lena Charlotte Schülke through the MedK-program. We acknowledge support from the Open Access Publication Fund of the University of Münster. The authors have no potential conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Humans; Male; Adult; Retrospective Studies; Testis; Spermatogenesis; Follicle Stimulating Hormone; Azoospermia; Sperm Count; Spermatozoa; Cluster Analysis; Oligospermia; Infertility, Male
PubMed: 38365879
DOI: 10.1093/humrep/deae013 -
Journal of Lasers in Medical Sciences 2023Biophoton emission, the spontaneous release of photons from living cells, has emerged as an attractive field of research in the study of biological systems. Scientists...
Biophoton emission, the spontaneous release of photons from living cells, has emerged as an attractive field of research in the study of biological systems. Scientists have recently discovered that changes in biophoton emission could serve as potential indicators of pathological conditions. This intriguing phenomenon suggests that cells might communicate and interact with each other through the exchange of these faint but significant light signals. Therefore, the present study introduces intercellular relationships with biophoton release to detect normal and abnormal cell functions to further achieve cellular interactions by focusing on cell and cell arrangement in disease conditions. Twenty male mice were assigned to control and busulfan groups. Five weeks after the injection of busulfan, the testis was removed, and then the stereological techniques and TUNEL assay were applied to estimate the histopathology of the testis tissue sections. The findings revealed that the ultra-weak biophoton emission in the control group was significantly lower than in the busulfan group. The oligospermia mice model showed that it significantly changed the spatial arrangement of testicular cells and notably decreased the testis volume, length of seminiferous tubules, and the number of testicular cells. The results of the TUNEL assay showed that the percentage of apoptotic cells significantly increased in the busulfan group. The ultra-weak biophoton emission from testis tissue was reduced in oligospermia mice. As a result, the decline of ultra-weak biophoton can indicate a change in cell arrangement, a decrease in intercellular interaction, and eventually disease.
PubMed: 38318218
DOI: 10.34172/jlms.2023.65 -
Reproductive Health Feb 2024Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male...
BACKGROUND
Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male mouse fertility has been established and the role of ZCWPW1 in human reproduction needs further investigation to verify.
METHODS
An infertile man with oligoasthenoteratozoospermia phenotype and his parents were recruited from West China Second University Hospital, Sichuan University. A total of 200 healthy Han Chinese volunteers without any evidence of infertility were recruited as normal controls, while an additional 150 infertile individuals were included to assess the prevalence of ZCWPW1 variants in a sporadic male sterile population. The causative gene variant was identified by Whole-exome sequencing and Sanger sequencing. The phenotype of the oligoasthenoteratozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay.
RESULTS
The proband exhibits a phenotype of oligoasthenoteratozoospermia, his spermatozoa show head defects by semen examination, Papanicolaou staining and electron microscope assays. Whole-exome sequencing and Sanger sequencing found the proband carries a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis shows a significant decrease in ZCWPW1 expression in the proband's sperm. By exogenous expression with ZCWPW1 mutant plasmid in vitro, the obvious declined expression of ZCWPW1 with the mutation is validated in HEK293T. After being treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells have a higher level of γ-H2AX, increased tail DNA and reduced H3K9ac level than WT-ZCWPW1 transfected cells. Furthermore, the Sperm Chromatin Dispersion assay revealed the proband's spermatozoa have high DNA fragmentation.
CONCLUSIONS
It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defects and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of oligoasthenoteratozoospermia.
Topics: Humans; Male; Chromatin; DNA Fragmentation; HEK293 Cells; Infertility, Male; Oligospermia; Semen; Sperm Head; Spermatozoa
PubMed: 38310235
DOI: 10.1186/s12978-024-01746-9 -
Nepal Journal of Epidemiology Dec 2023Nanoparticles (NPs) are small particles with a surface area ranging from 1 to 100 nm in diameter that are rampantly used in different fields, e.g., medicine,...
Nanoparticles (NPs) are small particles with a surface area ranging from 1 to 100 nm in diameter that are rampantly used in different fields, e.g., medicine, engineering, and others. Because of their unique properties, such as their tiny size, magnetic properties, quantum size effects, and macroscopic quantum tunnelling effects, they are crucial for a wide range of potential applications. NPs play a significant role in the treatment of vascular disorders, the production of vaccines, and the development of drug carriers for diverse therapies due to their bioavailability, targeting ability, and efficacy. However, significant risks to the environment and health are also associated with it. NPs cause necrotic plasma membrane rupture or apoptosis, which leads to cell death. NPs interfere with cell signalling, endosomal membranes, and organelles like the nucleus or mitochondria, affecting their function. NPs cause autophagic cell death, which causes a stress response and sterile inflammation. The primary routes for the entry of NPs into the human body are inhalation, ingestion, and skin contact. NPs accumulate in the respiratory system based on their size, shape, and surface properties. NPs can cause lung inflammation and fibrosis, disrupt the endocrine system by attaching to hormone receptors, and produce reactive oxygen species (ROS) associated with DNA damage, oligospermia, and male infertility. Carcinogenic properties of NPs cause mutations, apoptosis, and inflammatory responses. Collaborative research between ecologists and epidemiologists may enlighten ways to reduce the harmful effects of NPs.
PubMed: 38299042
DOI: 10.3126/nje.v13i4.61245 -
Cureus Dec 2023Purpose This article aims to report the first series of men with complete microduplications and their clinical and reproductive characteristics. Methods We sampled...
Purpose This article aims to report the first series of men with complete microduplications and their clinical and reproductive characteristics. Methods We sampled 3000 men who presented for reproductive urology evaluation from 2012-2020, of which 104 men underwent high-resolution Y-chromosome microarray testing, and five men were identified to have complete microduplications. Medical, surgical, and reproductive histories were obtained. Semen and hormonal parameters as well as response to fertility therapies were recorded. Results Five men were identified as having complete microduplications. The mean age was 33.75 years, representing 0.2% (5/3000) of men presenting for fertility investigation, 4.8% (5/104) of men undergoing microarray testing, and 21% (5/24) of men with abnormalities. Two of the men had prior undescended testicles and one had several autoimmune processes. The mean follicle-stimulating hormone (FSH) was 5.5 IU/L, luteinizing hormone (LH) 3.6 IU/L, and testosterone 14.56 nmol/L. One man was azoospermic, one man alternated between severe oligospermia and rare non-motile sperm, one had variable parameters, with one semen analysis demonstrating azoospermia and a second demonstrating a total motile sperm count (TMSC) of 4 ×10, one man was persistently oligospermic with TMSCs ranging 3.96-12.6 ×10, and one man initially had severe oligospermia, with a mean TMSC of 1.5 ×10, which increased to 21.7 ×10 after intervention (varicocele embolization, clomiphene citrate). This last man then fathered a spontaneous pregnancy. Conclusion complete microduplications are a rare cause of spermatogenic failure but not an uncommon form of abnormality. Clinically, they represent a heterogeneous group, having a variable reproductive potential. Cases should be managed on an individual basis.
PubMed: 38283528
DOI: 10.7759/cureus.51140 -
Aging Jan 2024Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different...
Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using Western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.
Topics: Rats; Male; Animals; Humans; Heme Oxygenase-1; Rats, Sprague-Dawley; NF-E2-Related Factor 2; Tripterygium; Oligospermia; Glycosides; Moxibustion; Asthenozoospermia; Infertility, Male; Seeds; Oxidative Stress; Antioxidants; Signal Transduction; Superoxide Dismutase; RNA, Messenger
PubMed: 38277193
DOI: 10.18632/aging.205475