Mesenchymal stem cell secretome: A promising therapeutic strategy for erectile dysfunction?

Objective: The secretome, comprising bioactive chemicals released by mesenchymal stem cells (MSCs), holds therapeutic promise in regenerative medicine. This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology, particularly for treating erectile dysfunction (ED), and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales, mechanisms, preclinical investigations, and therapeutic potential of the MSC secretome in this context. Methods: The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED. Subsequently, it delved into the existing knowledge regarding the MSC secretome, exploring its therapeutic potential. The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome. Results: Preclinical research indicated the effectiveness of the MSC secretome in treating various models of ED. However, the precise mechanisms of its therapeutic efficacy remain unknown. The review provided insights into the anti-inflammatory, pro-angiogenic, and trophic properties of the MSC secretome. It also discussed potential advantages, such as avoiding issues related to cellular therapy, including immunogenicity, neoplastic transformation, and cost. Conclusion: This review underscores the significant therapeutic potential of the MSC secretome in regenerative urology, particularly for ED treatment. While preclinical studies demonstrate promising outcomes, further research is essential to elucidate the specific mechanisms underlying the therapeutic efficacy before clinical application. The review concludes by discussing future perspectives and highlighting the challenges associated with the clinical translation of the MSC secretome in regenerative urology.

Examination of ejaculate fructose levels on male infertility patients at various times and centrifugation using semiautomatic method.

OBJECTIVE: Various factors, such as obstructive azoospermia, cause infertility in men. Biochemical examination of ejaculate, especially measurement of fructose, can be an additional investigation that can be used for this diagnosis in reproductive health. Examination of fructose is carried out after routine ejaculate analysis, resulting in prolonging the examination time so that it will affect the measurement of fructose level in the ejaculate and the accuracy of the diagnosis. This study aims to determine the best timing and procedure for measurement of fructose using a semiautomatic method. METHODS: This research is an analytic observational study conducted at Dr. Soetomo General Hospital, Surabaya. A total of 13 ejaculate samples from infertile male patients who met the inclusion criteria were evaluated. Each ejaculate was divided into eight aliquots that were examined for fructose using a semiautomated method after different intervals of time and centrifugation modalities. RESULTS: This study showed a significant difference in fructose levels when aliquots were centrifuged and examined immediately or after different interval of time (p=0.036). In addition, aliquots left standing for more than 60 minutes (p=0.012) and 120 minutes (p<0.001) before centrifugation, showed significantly lower levels compared to aliquots that were centrifuged and then immediately examined. CONCLUSIONS: We suggest that measuring fructose immediately after centrifugation is more reliable than measuring fructose left standing before or after centrifugation. Leaving the ejaculate standing will reduce the fructose level so that it does not resemble its real level.

Analyzing the factors that contribute to the development of embryological classical type of bladder exstrophy.

Bladder exstrophy is a rare congenital condition of the pelvis, bladder, and lower abdomen that opens the bladder against the abdominal wall, produces aberrant growth, short penis, upward curvature during erection, wide penis, and undescended testes. Exstrophy affects 1/30,000 newborns. The bladder opens against the abdominal wall in bladder exstrophy, a rare genitourinary condition. This study is vital to provide appropriate therapy choices as a basis to improve patient outcomes. This study may explain bladder exstrophy and provide treatment. Epispadias, secretory placenta, cloacal exstrophy, and other embryonic abnormalities comprise the exstrophy-spades complex. The mesenchymal layer does not migrate from the ectoderm and endoderm layers in the first trimester, affecting the cloacal membrane. Embryological problems define the exstrophy-aspidistra complex, which resembles epimedium, classic bladder, cloacal exstrophy, and other diseases. Urogenital ventral body wall anomalies expose the bladder mucosa, causing bladder exstrophy. Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure. External factors such as high maternal age, smoking moms, and high maternal body mass index have also been associated to bladder exstrophy. Valproic acid increases bladder exstrophy risk; chemicals and pollutants during pregnancy may increase bladder exstrophy risk. Bladder exstrophy has no identified cause despite these risk factors. Exstrophy reconstruction seals the bladder, improves bowel function, reconstructs the vaginal region, and restores urination.

Exploring the future potential of mesenchymal stem/stromal cells and their derivatives to support assisted reproductive technology for female infertility applications.

Women's infertility impacts the quality of life of both patients and couples and has multifaceted dimensions that increase the number of challenges associated with female infertility and how to face them. Female reproductive disorders, such as premature ovarian failure (POF), endometriosis, Asherman syndrome (AS), polycystic ovary syndrome (PCOS), and preeclampsia, can stimulate infertility. In the last decade, translational medicine has advanced, and scientists are focusing on infertility therapy with innovative attitudes. Recent investigations have suggested that stem cell treatments could be safe and effective. Stem cell therapy has established a novel method for treating women's infertility as part of a regeneration approach. The chief properties and potential of mesenchymal stem/stromal cells (MSCs) in the future of women's infertility should be considered by researchers. Due to their high abundance, great ability to self-renew, and high differentiation capacity, as well as less ethical concerns, MSC-based therapy has been found to be an effective alternative strategy to the previous methods for treating female infertility, such as intrauterine insemination, in vitro fertilization, medicines, and surgical procedures. These types of stem cells exert their beneficial role by releasing active mediators, promoting cell homing, and contributing to immune modulation. Here we first provide an overview of MSCs and their crucial roles in both biological and immunological processes. The next large chapter covers current preclinical and clinical studies on the application of MSCs to treat various female reproductive disorders. Finally, we deliberate on the extant challenges that hinder the application of MSCs in female infertility and suggest plausible measures to alleviate these impediments.

Current Progress in Stem Cell Therapy for Male Infertility.

Infertility has become one of the most common issues worldwide, which has negatively affected society and infertile couples. Meanwhile, male infertility is responsible for about 50% of infertility. Accordingly, a great number of researchers have focused on its treatment during the last few years; however, current therapies such as assisted reproductive technology (ART) are not effective enough in treating male infertility. Because of their self-renewal and differentiation capabilities and unlimited sources, stem cells have recently raised great hope in the treatment of reproductive system disorders. Stem cells are undifferentiated cells that can induce different numbers of specific cells, such as male and female gametes, demonstrating their potential application in the treatment of infertility. The present review aimed at identifying the causes and potential factors that influence male fertility. Besides, we highlighted the recent studies that investigated the efficiency of stem cells such as spermatogonial stem cells (SSCs), embryonic stem cells (ESCs), very small embryonic-like stem cells (VSELs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) in the treatment of various types of male infertility.

"Am I Masculine?" A metasynthesis of qualitative studies on traditional masculinity on infertility.

Background: The rate of infertility is increasing day by day. According to studies conducted worldwide, 30 million men are diagnosed with infertility. Cases of infertility are often associated with a failure to become male in society. Procreation and gender roles are often closely linked so that infertile men are often considered the second sex. Sometimes, this condition makes men question their masculinity. Methods: We performed a systematic review and metasynthesis with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline procedure on qualitative studies on ten databases exploring the experience of infertile men and their association with masculinity. Results: Twenty-four studies matched our question, and there are two major themes with eight subthemes that were obtained from the results of the metasynthesis of these studies. The impact of this gender issue is huge on men's health and their social interactions. As a result, gender issues provide a space for debate and a burden on men. Sometimes, men develop mental health problems. The topic of masculinity and infertility is at odds with feminism and is susceptible to the societal stigma that results from the hegemonic conception of masculinity. Interestingly, the men must accept reality and follow the treatment process for infertility, although it affects their psychological well-being. Conclusions: These findings provide insight for physicians, as treating infertility requires a multidisciplinary team that does not only address procreation issues. Social issues related to gender roles often bring patients into harmful and dangerous conditions. To address the gender issue in men globally in several dimensions, however, a large study in various populations is still required.

The interplay between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, erectile dysfunction, and Peyronie's disease: A meta-analysis of observational studies.

INTRODUCTION: This study aims to investigate the relationship between Neutrophil- Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR) with Erectile Dysfunction (ED) and Peyronie's disease (PD). METHODS: We conducted a meta-analysis of the observational study by searching for the appropriate keywords in eight databases. The risk of publication bias of the included studies was assessed by Egger's test and Kendall's t. The data extraction was carried out for each study and analysed using Revman 5.0. RESULTS: There were eleven eligible studies out of the 411 studies retrieved. Eight studies were conducted on cases of erectile dysfunction, and three studies on Peyronie's disease. There was a significant relationship between NLR, PLR and ED (SMD: 0.59, 95% CI: 0.33-0.85 and SMD: 0.64, 95% CI: 0.13-1.16, respectively). The same was also found for PD. The active phase of PD tended to have higher NLR (SMD: 0.68, 95% CI: 0.43-0.92) and PLR (SMD: 0.27, 95% CI: 0.06-0.49) compared to the chronic phase. No publication bias was found in both ED and PD studies. CONCLUSIONS: NLR and PLR indicate an ongoing inflammatory process in both ED and PD. These findings can be used as markers of treatment and prognosis of both diseases in sexual health care.

Semen and sex-steroid parameters among inflammatory bowel disease ulcerative colitis type according to rectal bleeding grade.

INTRODUCTION: Hypogonadism and inflammato-ry bowel disease (IBD) are often associated. This association may influence sexual and reproductive function in IBD, including sperm profile and sex steroid hormones. PATIENTS AND METHODS: This study included 59 IBD patients diagnosed with ulcerative colitis type IBD. Anamnesis was carried out regarding the history of the disease, along with a history of rectal bleeding. Evaluation proceeded with sperm and hormone examination if the patient agreed. RESULTS: Progressive motility sperm, immotile sperm, and normal sperm were found to be significantly different between the rectal bleeding groups. In grade 3 (more significant bleeding) progressive sperm (24.81 ± 5.85, p < 0.0001) and normal sperm (6.33 ± 12.56, p = 0.0003) rates tended to be lower, while immotile sperm tended to be higher (44.48 ± 11.21, p < 0.0001). Testosterone and free testosterone levels were also reported to be significantly different between groups, where grade 3 had lower levels 255.9 ± 30.08, p = 0.014 and 4.645 ± 0.5, p = 0.002 respectively. CONCLUSIONS: Our study shows that the degree of rectal bleeding influences sperm motility and morphology, as well as testosterone and free testosterone levels. These results can concern managing IBD patients to fulfill reproductive health care.

Novel Investigation of SARS-CoV-2 in COVID-19 Survivors' Semen in Surabaya, Indonesia

The emergence and the widespread of Coronavirus disease 2019 (COVID-19) demands an accurate detection method to establish a diagnosis. Real-time polymerase chain reaction (real-time PCR) is accounted for the perfect point of reference in detecting this virus. The notion that this virus also invades the male reproductive tract requires further investigation to prove the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the semen. This investigation was designed to detect SARS-CoV-2 in COVID-19 survivors semen. This study design was a cross-sectional examination and conducted between November 2020 and March 2021 in the Andrology Unit of Dr. Soetomo General Hospital and Professor Nidom Foundation, both located in the City of Surabaya, Indonesia. The sample was 34 male participants aged above 18 years old and had been confirmed COVID-19 by nasopharyngeal swab PCR test. Part of the semen was taken for real-time PCR testing with the QuantStudio 5 Applied Biosystem (AB) PCR machine and the kits utilized were the STANDARD M nCOV Real-Time Detection Kit and mBioCov-19 RT-PCR Kit. Furthermore, the mean of participants ages was 35.74 years old with 25% of them had had a history of primary infertility and 21.8% of secondary infertility. From the real-time PCR COVID-19 of the semen examination, this investigation found that 27 participants had been negatives (74.4%), six inconclusive (17.6%), and one positive (3%) of SARS CoV-2. In summary, SARS-CoV-2 could be found in the semen of COVID-19 survivors. This should be a concern for the potential impact of COVID-19 in male fertility and the possibility of transmission reproductively.