P–102 GM-CSF (granulocyte-macrophage colony-stimulating factor) as a sperm medium supplement improves sperm quality in Oligoastenoteratospermia (OAT) men by activating the PI3K/Akt pathway

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Tanhay. Kalat. Sabz ◽  
M Ashrafi ◽  
F Amjadi ◽  
Z Zandieh ◽  
E Hosseini ◽  
...  

Abstract Study question Can GM-CSF as a sperm medium supplement improve sperm quality in OAT men? Summary answer GM-CSF can be used to improve sperm quality in OAT men by activating the PI3K/Akt pathway. What is known already OAT patients have very low sperm parameters, including morphology, count, and motility, which can adversely affect the results of assisted reproduction technologies. It seems the development of sperm media is necessary to improve the sperm parameters of these patients. GM-CSF is a natural growth factor produced by the reproductive organs, culture media supplemented with GM-CSF is widely commercially available and enhances the embryo development and implantation rate. Studies show that this growth factor in the semen of infertile men is lower than that of fertile men. However, there is no study to assess the effect of GM-CSF on sperm quality. Study design, size, duration In the present study, Semen specimens were collected from 20 OAT patients who have male infertility factors, according to WHO criteria. After the swim-up washing procedure, each of the samples is divided into two groups; experiment, and control. In the experimental group, samples are incubated with a medium containing 2 ng/ml GM-CSF for one hour, yet, in the control group, the sperms are incubated without GM-CSF for the same time. Participants/materials, setting, methods The sperm motility was examined with phase-contrast microscopy, Eosin-nigrosin staining method was used to assess sperm viability. The expression of sperm glucose transporters (GLUT 1, 3) was determined using immunofluorescent staining, the ratio of pAkt to total Akt was assessed by the Western blotting method. Image J software was used to quantify results; the data was analyzed by SPSS software. P-value<0.05 was considered statistically significant. Main results and the role of chance As compared to the control group, supplementation with GM-CSF improved sperm progressive motility, enhanced GLUT 1 and 3, and p-AKT/AKT expression (P < 0.05). There was no significant difference between the viability of the control and experimental groups. Limitations, reasons for caution This study needs further investigations, including Real-time PCR for the genes of this signaling pathway which is ongoing. Wider implications of the findings: We showed for the first time that GM-CSF can improve sperm quality by influencing motility and energy metabolism in spermatozoa which can be affected by increasing the phosphorylation of AKT. This growth factor could be an appropriate supplement in sperm media for OAT patients. Trial registration number IRCT20200519047508N1

2015 ◽  
Vol 119 (6) ◽  
pp. 663-669 ◽  
Author(s):  
Yi-Yuan Lin ◽  
Shin-Da Lee ◽  
Chia-Ting Su ◽  
Tsung-Lin Cheng ◽  
Ai-Lun Yang

Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.


2018 ◽  
Vol 1 (2) ◽  
pp. 1-17
Author(s):  
Fahcreza ◽  
Elsa Iskandar ◽  
Rachmat Hidayat ◽  
Petty Purwanita ◽  
Anang Tribowo ◽  
...  

Abstract Background: Chemical trauma to the cornea is an emergency condition of the eye that requires early diagnosis and good treatment. Alkaline have ability to saponify fatty acids in cells and cell membranes which can make penetration into the stroma and destroy proteoglycans and collagen in cells. Aloe vera (AV) contains several active substances that are reported to have anti-inflammatory, immunomodulatory, and wound healing effects. AV has been reported to accelerate the healing process of corneal epithelial defects by increasing fibroblast proliferation, collagen production and growth factor production. This study aims to determine the difference between the effect of aloe vera extract with a concentration of 10%, 20%, 40% and BSS on the healing of extensive corneal lesions in white wistar rats alkaline trauma models. Method: This study was an experimental study with a pre and posttest only with control group design in vivo approach to 30 Wistar white rats which were divided into 5 treatment groups for 3 days. Comparative analysis of effectiveness using the ANNOVA test or the Kruskal Wallis test and continued by the post hoc test. Results: Based on the one way ANOVA test there was a statistically significant difference in effectiveness between the five treatment groups on the percentage of corneal wound healing area and TGF-β expression with an assessment of p = 0,000 each. The administration of alloevera (AV) concentration of 20% had a significant difference in percentage of healing of corneal lesions and TGF-β expression compared with other treatment groups with p = 0,000 each. Large differences in the area of corneal lesions in the 40% AV group were -0.45 in the BBS group, 0.146 in the 10% AV group, 0.493 in the 20% AV group. The difference in the AV group 10% was 0.30 in the BBS group, -064 in the AV group 20%, and -0.14 in the AV group 40%. However, TGFβ expression in the normal control group that did not receive treatment was 54.94 (53.21-56-12). TGFβ levels in the BSS group were 10.44, the 10% aloe vera group was 25.43, 47.99 for the 20% aloe vera group and 37.95 for the 40% aloe vera group. Conclusion: There is a difference between the effect of aloe vera extract with concentrations of 10%, 20%, 40% and BSS on the extensive healing of corneal lesions in white wistar rats with alkaline chemical trauma models.


Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.


2019 ◽  
Vol 17 ◽  
pp. 205873921984406
Author(s):  
Tao Zheng ◽  
Qingyun Zhou ◽  
Zhe Chen ◽  
Qinning Wang

The study aimed to study the correlation between expression levels of interleukin-37 (IL-37), granulocyte macrophage colony-stimulating factor (GM-CSF), and C-reactive protein (CRP) in peripheral blood and the status of atherosclerosis (AS) and plaque stability and to confirm the clinical significance of these inflammatory factors in the pathogenesis of AS. A total of 64 AS patients (case group) were selected and divided into unstable plaque group (group A, 28 cases) and stable plaque group (group B, 36 cases) according to the color ultrasonography results of arterial vessels. At the same time, 30 healthy subjects were classified into the control group. General information of the enrolled subjects was collected, including levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), CRP, and homocysteine (Hcy). The expression levels of IL-37 and GM-CSF in the serum of peripheral blood samples collected from these subjects were measured by enzyme-linked immunosorbent assay (ELISA). There was no significant difference between the case group and the control group in the levels of TC, TG, HDL, and LDL ( P > 0.05). However, the expression level of Hcy in the case group was significantly higher than that in the control group ( P < 0.05). Compared with the control group, the expression levels of IL-37, GM-CSF, and CRP in the case group were significantly increased ( P < 0.05). In addition, compared with group B, the expression level of GM-CSF in group A was significantly increased ( P < 0.05), while no significant difference was detected between group A and group B in the expression levels of IL-37 and CRP ( P > 0.05). In conclusion, inflammatory factors IL-37, GM-CSF, CRP, and Hcy were all involved in the pathogenesis of AS, and the increased levels of GM-CSF were closely related to the progress of unstable plaques. These results may aid the early diagnosis/treatment of AS.


2011 ◽  
Vol 23 (1) ◽  
pp. 110
Author(s):  
M. A. Coutinho da Silva ◽  
C. R. F. Pinto ◽  
J. M. Young ◽  
K. Cole

Magnetic-activated cell sorting (MACS) has been used successfully in humans to remove apoptotic sperm from the ejaculate. Annexin V-conjugated microbeads recognise sperm with externalized phosphatidylserine, which is considered one of the features of apoptosis, and the labelled sperm is separated by MACS. The goals of the study were to determine if MACS can be used to separate apoptotic sperm from the ejaculate of stallions; and to determine if removal of apoptotic sperm improves the quality of stallion sperm. Our hypothesis was that MACS would improve semen quality by removing apoptotic sperm, resulting in samples with higher motility and viability. Two ejaculates from three different stallions of good fertility were used. Sperm were diluted with Tyrode’s albumin lactate pyruvate (TALP) and incubated with annexin V-conjugated microbeads for 15 min at 37°C. Control samples were incubated in the absence of annexin V microbeads. The suspension was then loaded into the separation column containing iron globes, which were fitted in a magnet (MiniMACS; Miltenyi Biotec Inc., Auburn, CA, USA). The effluent sample containing annexin-negative sperm was collected and then, the column was removed from the magnetic field and rinsed with TALP to collect the annexin-positive cells. Sperm viability, motility, morphology and caspase activation were determined in all three samples: control, annexin-negative, and annexin-positive. Data were evaluated by ANOVA and individual comparisons were performed by Tukey’s hsd test. Significance was set at P < 0.05 and data is presented as means ± SEM (Table 1). The main effect of stallion was significant only for sperm motility parameters. Sperm recovery rate following MACS was 46 ± 3%. In conclusion, the use of MACS was effective in removing apoptotic sperm from the ejaculate. The annexin-positive population displayed a higher proportion of sperm with activated caspases and lower membrane integrity and motility. However, removal of apoptotic sperm from the ejaculate did not improve sperm parameters in the annexin-negative group compared to control group. In addition, sperm morphology was not affected by MACS. Further studies are necessary to determine if MACS could be used successfully to improve sperm quality from subfertile stallions and frozen semen. Table 1.Sperm parameters following annexin V MACS (mean ± SEM) The authors are thankful to Mark Williams at Miltenyi Biotec Inc. for providing supplies; and Dr Ashok Agarwal at The Center for Reproductive Medicine, Cleveland Clinic, for scientific input.


2020 ◽  
Vol 35 (2) ◽  
pp. 340-354 ◽  
Author(s):  
Emma Norrman ◽  
Max Petzold ◽  
Christina Bergh ◽  
Ulla-Britt Wennerholm

Abstract STUDY QUESTION Do children conceived after ICSI have similar school performance as children born after IVF? SUMMARY ANSWER Children born after ICSI have similar school performance compared to children born after IVF. WHAT IS KNOWN ALREADY Studies concerning the cognitive skills of children born after ICSI have shown diverging results. STUDY DESIGN, SIZE, DURATION This nationwide, register-based cohort study included all singleton children born after ICSI (n = 6953), IVF (n = 11 713) or spontaneous conception (SC) (n = 2 022 995), in Sweden between 1985 and 2006. PARTICIPANTS/MATERIALS, SETTING, METHODS Singleton children born after ICSI were identified in national IVF registers, cross-linked with the Medical Birth Register (MBR), the National Patient Register (NPR) and the Swedish Cause of Death Register (CDR) for characteristics and medical outcomes. Data on school performance, parental education and other parental characteristics were obtained through cross-linking to the National School Registry and to Statistics Sweden. The main control group, which consisted of children born after IVF, was identified in the national IVF registries while the second control group, consisting of children born after SC, was identified from the MBR. Simple and multivariable linear regression was used for analysis of continuous variables, and logistic regression was used for the analysis of binary outcomes. Adjustments were made for sex, year of birth, maternal smoking during pregnancy, parental age, parity, parental region of birth, parental level of education and frozen embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE In the adjusted analyses, there was no significant difference between ICSI and IVF children for total score (adjusted odds ratios (AORs) 1.03; 95% CI −0.22 to 2.28; P = 0.11), specific subjects, qualifying for secondary school (AOR 1.02; 95% CI 0.82–1.26; P = 0.87) or poor school performance (AOR 0.92; 95% CI 0.75−1.14; P = 0.47). In the third grade, children born after ICSI had a significantly lower chance of passing all of the subtests in Mathematics (AOR 0.89; 0.83–0.96; P = 0.002) and Swedish (AOR 0.92; 0.85–0.99; P = 0.02) compared to children born after SC. When cross-linking children with missing data on school performances (2.1% for ICSI, 2.0% for IVF and 2.3% for SC) with the Cerebral Palsy Follow-up Register (CPUP) for cerebral palsy, 2.7% of ICSI children, 5.7% of IVF children and 1.7% of SC children without registered education were found. When cross-linking children with missing data on school performances with the NPR for mental retardation, 29.9% of ICSI children, 32.6% of IVF children and 35.0% of SC children with missing data were registered under such a diagnosis. LIMITATIONS, REASONS FOR CAUTION The main limitation was that test scores were missing in a small percentage in both ICSI and IVF children. Although we were able to cross-link this subpopulation with the CPUP and the NPR, these diagnoses only partly explained the missing scores. Other limitations were unmeasured and unknown possible confounders, such as information about infertility diagnoses and indication for ICSI, were not available. WIDER IMPLICATIONS OF THE FINDINGS These findings are important to most countries where IVF and ICSI are used since there may be differences in choice of procedure. In recent years, there has been an increasing trend towards using ICSI not only for treatment of male infertility but also when the sperm quality is normal. Our results indicate that the school performance of children born after ICSI is reassuring. STUDY FUNDING/COMPETING INTEREST(S) Financial support was received through Sahlgrenska University Hospital (ALFGBG – 70 940), Hjalmar Svensson Research Foundation and Nordforsk, project number 71 450. None of the authors declare any conflict of interest. TRIAL REGISTRATION NUMBER N/A


2019 ◽  
Vol 7 ◽  
pp. 2050313X1983415
Author(s):  
José Arturo Mora Rodríguez ◽  
Leonardo M Porchia ◽  
Felipe Camargo ◽  
Esther López-Bayghen

Male patients suffering from oligoasthenoteratozoospermia typically failed to achieve pregnancy, even with assisted reproductive technologies. Growth hormone and insulin-like growth factor 1 have been shown to regulate sperm quality parameters; therefore, the insulin-like growth factor 1 supplement could improve sperm parameters. Here, we determine the effect insulin-like growth factor 1 has on sperm parameters in a patient suffering from oligoasthenoteratozoospermia. A 47-year-old male was administered once a day 1.5 IU of insulin-like growth factor 1 by intradermal injection for 2 months. Seminogram analysis was performed before and after. Treatment with insulin-like growth factor 1 resulted in a 15.5-fold improvement in sperm concentration (1.1 × 106 vs 18.3 × 106 per mL), 71.4% change in volume (0.7 vs 1.2 mL), increased progressive motility (2% vs 43%), and the total volume of sperm with progressive motility (0% vs 23.6%). Here, we show that administering a daily dose of insulin-like growth factor 1 can improve sperm quality parameters.


2009 ◽  
Vol 59 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Arash Kheradmand ◽  
Majid Taati ◽  
Homayoon Babaei

AbstractAlthough ghrelin acts as a modulator of feeding behavior and energy metabolism in the central nervous system, recent studies have implicated the peripheral actions of ghrelin in reproductive tissues. Here, we investigated the effects of chronic administration of ghrelin on the motility, plasma membrane integrity and concentration of rat spermatozoa. 45-d male Wistar rats were scheduled for the study and were divided into control and treatment groups. In the treatment group, 1 nmol of ghrelin was administered as sc injection for 10 consecutive days or vehicle (physiological saline) to the control rats. Sperm collection was achieved by killing of the rats on days 15, 25 and 50 after first injection. Total sperm motility and forward progressive movement did not exhibit significant difference during the experiment, although, there was a tendency for greater motion rate on d 15 and 25 in the treated rats compared to the control group. Plasma membrane integrity (HOS-reacted spermatozoa) was significantly higher in the treated animals, especially on day 15 as well as day 25, because of possible antioxidant properties of ghrelin. This value was statistically higher on day 15 than that of day 25 (P <0.05). Likewise, there was a significant correlation between the FPM (P <0.0001, r = 0.79) and TSM (P <0.01, r = 0.52) with the HOS test percentage in the treatment group. It was not observed statistically difference in the sperm concentration between groups during all of the experimental days. In conclusion, chronic administration of ghrelin (similar to induced by energy deficiency such as fasting) increased the integrity of sperm membrane, however, the sperm motility and concentration did not display any alterations.


Author(s):  
Fadhil Jawad Al-Tu'ma ◽  
Anaam Hato Kadhim ◽  
Anaam Hato Kadhim ◽  
Saif Sami Al-Mudhaffar

Coronary artery disease (CAD) is a clinical manifestation resulting from a narrowing of epicardial coronary arteries that supply blood and oxygen to the heart. Coronary artery disease is mostcommonlydue to atherosclerotic occlusion of the coronary arteries.Fibroblast growth factor 23 (FGF23) is a circulating peptide hormone secreted by bone cells,regulating phosphate and vitamin D metabolism. Several recent observational studies reported an independent association of circulating FGF23 with several cardiovascular disease (CVD) risk factors including left ventricular hypertrophy and vascular dysfunction,CVD progression and incident clinical CVD eventsand mortality.Apolipoprotein A1 (ApoA1) is the primary protein associated with high-density lipoprotein (HDL) particles,and plays a central role in reverse cholesterol transport. HDL cholesterol (HDL-C) and ApoA1 concentrations are inverlassely related to the risk for coronary artery disease. To find the role of fibroblast growth factor-23 in coronary artery disease and its associationwith Apolipoprotein-A1.This ccross –sectionalstudyincluded 42 elective patients attending the cardiology unit and the results of those patients were compared with 40 healthy control group. Blood samples were obtained for measurements of (FGF-23,troponin I,Apo-A1,total creatine kinase activity,urea,creatinine and lipid profile).The obtained results showed that there was a significant difference in serum FGF-23 in coronary artery disease (367.52 ± 128.52 pg/ml) as compared with the control (165.41 ± 53.65 pg/ml) (p< 0.05). There was a significant differences in Apo-A1 in coronary artery disease (2.03±0.90 mg/ml) as compared with the control (1.49 ± 0.25 mg/ml) (P = 0.014).There was a significant difference in age between CAD (58.66±8.85) and control group (51.125 ± 11.71) (P<0.005).There was a significant difference in TG where control (99.50 ± 21.59) differ from CAD (142.05 ± 66.24) (P = 0.006).According to the results that were shown in the tables, we can be conclude that higher levels of FGF23 and Apo-A1 may be associated with complications and mortality of CAD beside its associating with atherosclerosis in the Iraqi patients.


Author(s):  
Serhat Engin ◽  
Muammer Kürşat Fırat ◽  
Osman Özden ◽  
Cüneyt Suzer ◽  
Müge Hekimoğlu ◽  
...  

The present study aimed to evaluate the activation characteristics of the leaping mullet spermatozoa and diluted with four different media (D1, D2, D3, D4) for 250 h at 4±2°C. The semen was collected from nine wild fish in Homa Lagoon, İzmir, Turkey in July, during reproductive season. In each trial (n = 9), semen samples were collected and mixed to reduce sperm quality variation to obtain the required gametes for the experiment. The semen was activated with natural seawater (salinity of 34, pH 7.9 and 4±2°C) to determine: motility time, motility rate and viability of sperm. Dilution with inactivation media 1:3 increased motility time of diluted semen than control group. At the end of the experiment, no significant difference was found for the duration of survival in the D2 and D4 groups. The highest survival rate was found in D2 group.


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