From spermatogonia to spermatozoa: Filling gaps in andrology at the 16th Network of Young Researchers in Andrology meeting.

The 16th Network of Young Researchers in Andrology meeting, hosted at the Sleepwell Hostel in Brussels, Belgium, was the first Network of Young Researchers in Andrology meeting as the young arm of the European Academy of Andrology. Over three days, this vibrant event provided a valuable platform for early-career researchers in andrology to present and discuss their research. With 41 attendees from 12 different countries, the meeting featured a diverse scientific program including keynote lectures from six world-leading experts, covering a broad range of topics in andrology. The 16th Network of Young Researchers in Andrology meeting showcased advancements in fertility preservation, single-cell applications, in vitro testis modeling, and epigenetics. Networking opportunities were a key highlight, featuring a scientific speed-dating session and a networking dinner designed to foster meaningful connections and collaborations among participants. The meeting concluded with a workshop on the science of sleep, offering attendees practical strategies to enhance their rest and well-being. Overall, the 16th Network of Young Researchers in Andrology meeting significantly advanced the audience's knowledge, strengthened the network of young researchers, and underlined Network of Young Researchers in Andrology's commitment to supporting and collaborating with emerging scientists in the andrology community.

Effect of New Antidiabetics on Steatosis in Nerve Tissues and Nerve Conduction Velocity: Possible Role of Nerve Growth Factor (NGF)/Synaptophysin and Nrf2/HO-1 Pathways.

OBJECTIVES: The current study aims to investigate the impact of the GLP1 analog (semaglutide) and SGLT2 inhibitor (dapagliflozin) on nerve functions, morphology, and the underlying mechanisms involving nerve growth factor (NGF)/synaptophysin and Nrf2/HO-1 pathways in obese rats. METHODS: Forty male Sprague Dawley rats, aged six to eight weeks, were classified into five groups; normal group (high-fat diet {HFD} for 12 weeks, metformin group (HFD for 12 weeks + metformin in last four weeks), dapagliflozin group (HFD for 12 weeks +dapagliflozin in last four weeks, semaglutide group (HFD for 12 weeks + semaglutide in last four weeks). At the end of the experiment, the sciatic nerve was collected for nerve conduction study, oxidative stress marker (malondialdehyde, i.e., MDA), real-time polymerase chain reaction (PCR) study (for HO-1 and Nrf2), oil red O staining, electron microscopic examination and immunohistochemistry for NGF and synaptophysin. RESULTS: The HFD group showed a significant rise in blood glucose, serum lipids, homeostatic model assessment (HOMA) index, lipid deposition in nerve tissues, and lipid peroxidation (MDA) in nerve tissues with significant attenuation in nerve conduction velocity (NCV), the expression of Nrf2 and HO-1 genes and significant attenuation in area stained with NGF and synaptophysin. On the other hand, pretreatment with either dapagliflozin or semaglutide led to considerable enhancement in the deteriorated serum and nerve tissue parameters and reversed the pathological changes. CONCLUSION: New antidiabetic drugs like SGLT2 inhibitors (more powerful) and GLP1 analog might have neuroprotective beneficial effects besides controlling the glycemic state in obese rats. This effect may result from reduced oxidative stress and increased Nrf2 levels, HO-1, synaptophysin, and NGF in the nerve tissues of obese rats.

Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis.

BACKGROUND: Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy. OBJECTIVE: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis. METHODS: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI). RESULTS: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo. CONCLUSION: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men. PROSPERO: CRD42023430179.

Effect of intermittent fasting on adriamycin-induced nephropathy: Possible underlying mechanisms.

PURPOSE: Intermittent fasting (IF) has been shown to induce a well-organized adaptive defense against stress inside the cells, which increases the production of anti-oxidant defenses, repair of DNA, biogenesis of mitochondria, and genes that combat inflammation. So, the goal of the current investigation was to identify the effects of IF on rats with adriamycin (ADR)-induced nephropathy and any potential underlying mechanisms. METHODS: Four groups of 40 mature Sprague-Dawley male rats were allocated as follow; control, fasting, ADR, and ADR plus fasting. After 8 weeks of ADR administration urine, blood samples and kidneys were taken for assessment of serum creatinine (Cr), BUN, urinary proteins, indicators of oxidative damage (malondialdehyde (MDA), reduced glutathione (GSH) and Catalase (CAT) levels), histopathological examinations, immunohistochemical examinations for caspase-3, Sirt1, aquaporin2 (AQP2) and real time PCR for antioxidant genes; Nrf2, HO-1 in kidney tissues. RESULTS: IF significantly improved serum creatinine, BUN and urinary protein excretion, oxidative stress (low MDA with high CAT and GSH), in addition to morphological damage to the renal tubules and glomeruli as well as caspase-3 production during apoptosis. Moreover, IF stimulates significantly the expression of Sirt1 and Nrf2/HO-1 and AQP2. CONCLUSION: AQP2, Sirt1, Nrf2/HO-1 signaling may be upregulated and activated by IF, which alleviates ADR nephropathy. Enhancing endogenous antioxidants, reducing apoptosis and tubulointerstitial damage, and maintaining the glomerular membrane's integrity are other goals.

Empowering tomorrow's leaders: the impact of the 15th Network of Young Researchers in Andrology (NYRA) meeting on male reproductive health and interdisciplinary collaboration.

The 15th Network of Young Researchers in Andrology (NYRA) meeting, held at the Palace de Caux, Switzerland, served as a valuable platform to disseminate cutting-edge research and facilitate interactions among early-career researchers and trainees in andrology from around the world. Preceding the 22nd European Testis Workshop, the 2-day event brought together participants from a variety of countries to discuss a range of topics pertaining to men's reproductive health and biology. Specific focuses included piRNAs in mammalian reproduction, biomolecules enhancing sperm physiology, advances in in vitro spermatogenesis, reproductive strategies across species, and career development. A dedicated 'scientific speed-dating' social event also stood out, encouraging cross-disciplinary collaborations and strengthening ties within the scientific community. The high participation rate of the meeting highlighted its value in connecting the andrology community. Finally, the announcement of NYRA's merger with the European Academy of Andrology (EAA) marked a pivotal moment, enabling NYRA to support young researchers while collaborating with the EAA to advance andrology research. The 15th NYRA meeting played a crucial role in enhancing knowledge dissemination and andrology research, empowering young researchers, and addressing key challenges in male infertility.

Effect of Melatonin on Alpha Synuclein and Autophagy in Dopaminergic Neuronal Differentiation of Adipose Mesenchymal Stem Cells.

Background: The current work investigated the effect of melatonin on differentiation of adipose mesenchymal stem cells (AD-MSCs) into dopamine producing cells and its effect on autophagy process and alpha-Synuclein (α-Syn) secretion. Methods: AD-MSCs were characterized by flow cytometry and divided into 4 groups; i) control group (AD-MSCs without any treatment), ii) M+MSCs group (MSCs treated with 1 µM melatonin for 12 days), iii) DN group (MSCs cultured in neurobasal A medium and essential neuronal growth factors for 12 days) and iv) DN+M group (MSCs cultured in neurobasal A medium and 1µM melatonin for 12 days. By the end of experiments, the dopamine and α-Syn levels using ELISA, the expression of MAP-2, m-TOR and α-Syn genes at the level of mRNA and detection of autophagosomes formation using transmission electron microscope were performed. Results: We found that the isolated cells were MSCs due to their positivity expression for CD105 and CD90 and negativity expression for CD34 and CD45. The concentration of dopamine was significantly higher and α-Syn concentration was significantly lower in DN+M group when compared to other groups (P< 0.005). Also, this group showed the highly expression for MAP-2 gene and less expression for m-TOR and α-Syn genes (P< 0.005). Moreover, there was significantly increase in autophagosomes formation in this group than another group (P< 0.005). Conclusions: It is concluded that the melatonin promotes the differentiation of rat AD-MSCs into dopaminergic cells via induction of autophagy process and reduction of α-Syn secretion.

Possible Role of Oxidative Stress and Nrf2/HO-1 Pathway in Pentylenetetrazole-induced Epilepsy in Aged Rats.

Background: To examine the impact of aging on the response of rats to pentylenetetrazole (PTZ)-induction of epilepsy and the possible role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase (HO)-1 pathway in this response. Methods: Forty male albino rats were equally allocated into 4 groups; 1) Young control (YC) group, aged 8-12 weeks, 2) Old control (OC) group, aged 24 months, 3) PTZ-Young group: young rats received PTZ (50 mg/Kg, i.p. every other day) for 2 weeks and 4) PTZ-Old group: as group 3 but rats were old. The seizure score stage and latency to the first jerk were recorded in rats. Redox state markers in brain tissues including malondialdehyde (MDA), catalase and total antioxidant capacity (TAC) were evaluated. Also, the expression of Nrf2 and HO-1 genes were measured in the brain tissues. Results: Old rats showed an early and a significant rise in the seizure score with PTZ administration and a significant drop in the seizure latency compared to young rats (P <0.01). Also, old rats showed a significantly higher MDA concentration and a significantly lower TAC and catalase activity than young rats (P <0.01). Moreover, the expression of Nrf2 and HO-1 was significantly lowered in old rats compared to young rats with PTZ administration (P < 0.01). Conclusion: Aging increases the vulnerability of rats to PTZ-induced epilepsy. An effect might come down to the up-regulation of oxidative stress and the down regulation of antioxidant pathways including Nrf2 and HO-1.

Hepatoprotective Effects of Hyaluronic Acid-Preconditioned Bone Marrow Mesenchymal Stem Cells against Liver Toxicity via the Inhibition of Apoptosis and the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: Doxorubicin (DOX) is widely used to treat a variety of malignancies in both adults and children, including those of the bladder, breast, stomach, and ovaries. Despite this, it has been reported to cause hepatotoxicity. The recent discovery of bone marrow-derived mesenchymal stem cells' (BMSCs) therapeutic effects in the context of liver diseases suggests that their administration plays a part in the mitigation and rehabilitation of drug-induced toxicities. OBJECTIVES: This study investigated whether bone BMSCs could reduce DOX-induced liver damage by blocking the Wnt/ß-catenin pathway that causes fibrotic liver. MATERIALS AND METHODS: BMSCs were isolated and treated with hyaluronic acid (HA) for 14 days before injection. Thirty-five mature male SD rats were categorized into four groups; group one (control) rats were supplemented with saline 0.9% for 28 days, group two (DOX) rats were injected with DOX (20 mg/kg), group three (DOX + BMSCs) rats were injected with 2 × 106 BMSCs after 4 days of DOX injection, group four (DOX + BMSCs + HA) rats were injected with 0.1 mL BMSCs pretreated with HA after 4 days of DOX. After 28 days the rats were sacrificed, and blood and liver tissue samples were subjected to biochemical and molecular analysis. Morphological and immunohistochemical observations were also carried out. RESULTS: In terms of liver function and antioxidant findings, cells treated with HA showed considerable improvement compared to the DOX group (p < 0.05). Moreover, the expression of inflammatory markers (TGFß1, iNos), apoptotic markers (Bax, Bcl2), cell tracking markers (SDF1α), fibrotic markers (ß-catenin, Wnt7b, FN1, VEGF, and Col-1), and ROS markers (Nrf2, HO-1) was improved in BMSCs conditioned with HA in contrast to BMSCs alone (p < 0.05). CONCLUSION: Our findings proved that BMSCs treated with HA exert their paracrine therapeutic effects via their secretome, suggesting that cell-based regenerative therapies conditioned with HA may be a viable alternative to reduce hepatotoxicity.