scholarly journals Granulocyte Colony-Stimulating Factor Restored Impaired Spermatogenesis and Fertility in an AML-Chemotherapy Mice Model

2021 ◽  
Vol 22 (20) ◽  
pp. 11157
Author(s):  
Yulia Michailov ◽  
Ali AbuMadighem ◽  
Eitan Lunenfeld ◽  
Joseph Kapelushnik ◽  
Mahmoud Huleihel
Keyword(s):  
Male Fertility ◽  
Inflammatory Cytokine ◽  
Sperm Parameters ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Post Injection ◽  
Colony Stimulating Factor ◽  
Expression Levels ◽  
First Time ◽  
Stimulating Factor

Leukemia and treatment of male patients with anticancer therapy (aggressive chemotherapy and/or radiotherapy) may lead to infertility or even permanent male sterility. Their mechanisms of spermatogenesis impairment and the decrease in male fertility are not yet clear. We showed that under acute myeloid leukemia (AML) conditions, alone and in combination with cytarabine (CYT), there was significant damage in the histology of seminiferous tubules, a significant increase in apoptotic cells of the seminiferous tubules, and a reduction in spermatogonial cells (SALL and PLZF) and in meiotic (CREM) and post-meiotic (ACROSIN) cells. In addition, we showed a significant impairment in sperm parameters and fertilization rates and offspring compared to control. Our results showed a significant decrease in the expression of glial cell line-derived neurotrophic factor (GDNF), macrophage colony-stimulating factor (MCSF) and stem cell factor (SCF) under AML conditions, but not under cytarabine treatment compared to control. In addition, our results showed a significant increase in the pro-inflammatory cytokine interleukin-1 (IL-1) alpha in whole testis homogenates in all treatment groups compared to the control. Increase in IL-1 beta level was shown under AML conditions. We identified for the first time the expression of GCSF receptor (GCSFR) in sperm cells. We showed that GCSF injection in combination with AML and cytarabine (AML + CYT + GCSF) extended the survival of mice for a week (from 6.5 weeks to 7.5 weeks) compared to (AML + CYT). Injection of GCSF to all treated groups (post hoc), showed a significant impact on mice testis weight, improved testis histology, decreased apoptosis and increased expression of pre-meiotic, meiotic and post- meiotic markers, improved sperm parameters, fertility capacity and number of offspring compared to the controls (without GCSF). GCSF significantly improved the spermatogonial niche expressed by increased the expression levels of testicular GDNF, SCF and MCSF growth factors in AML-treated mice and (AML + CYT)-treated mice compared to those groups without GCSF. Furthermore, GCSF decreased the expression levels of the pro-inflammatory cytokine IL-12, but increased the expression of IL-10 in the interstitial compartment compared to the relevant groups without GCSF. Our results show for the first time the capacity of post injection of GCSF into AML- and CYT-treated mice to improve the cellular and biomolecular mechanisms that lead to improve/restore spermatogenesis and male fertility. Thus, post injection of GCSF may assist in the development of future therapeutic strategies to preserve/restore male fertility in cancer patients, specifically in AML patients under chemotherapy treatments.

scholarly journals Interleukin-34, a Novel Paracrine/Autocrine Factor in Mouse Testis, and Its Possible Role in the Development of Spermatogonial Cells In Vitro

2020 ◽  
Vol 21 (21) ◽  
pp. 8143
Author(s):  
Alaa Sawaied ◽  
Eitan Lunenfeld ◽  
Mahmoud Huleihel
Keyword(s):  
Seminiferous Tubules ◽  
Isolated Cells ◽  
Proliferation And Differentiation ◽  
Endocrine Factors ◽  
First Time ◽  
Old Mice ◽  
Stimulating Factor ◽  
Autocrine Factor ◽  
Peritubular Cells

Spermatogenesis is the process of spermatogonial stem cell (SSC) proliferation and differentiation to generate sperm. This process is regulated by cell–cell interactions between Sertoli cells and developing SSCs by autocrine/paracrine and endocrine factors. It is also affected by cells in the interstitial compartment, such as Leydig cells and peritubular cells. Here, we demonstrate, for the first time, the presence of interleukin-34 (IL-34) in Leydig, Sertoli, and peritubular cells and in the premeiotic, meiotic, and postmeiotic cells. Its receptor, colony-stimulating factor-1 (CSF-1), has already been demonstrated in Leydig, Sertoli, premeiotic, and meiotic cells. IL-34 was detected in testicular homogenates and Sertoli cell-conditioned media, and was affected by mouse age. We showed that the addition of IL-34 in vitro to isolated cells from the seminiferous tubules of 7-day-old mice, using the methylcellulose culture system (MCS), increased the percentages and expression of the premeiotic cells (VASA), the meiotic cells (BOULE), and the meiotic/postmeiotic cells (ACROSIN) after four weeks of culture, when examined by immunofluorescence staining (IF) and qPCR analysis. It is possible to suggest that IL-34 is a novel paracrine/autocrine factor involved in the development of spermatogenesis. This factor may be used in future therapeutic strategies for the treatment of male infertility.

scholarly journals Varying expression levels of colony stimulating factor receptors in disease states and different leukocytes

2000 ◽  
Vol 32 (4) ◽  
pp. 210-215 ◽  
Author(s):  
Kyo Young Lee ◽  
Byung-Gyu Suh ◽  
Jong Wan Kim ◽  
Won Bae Lee ◽  
So-Young Kim ◽  
...  
Keyword(s):  
Colony Stimulating Factor ◽  
Expression Levels ◽  
Disease States ◽  
Stimulating Factor

Abstract 22: Monocyte Chemotactic Protein-1 and Macrophage Colony-Stimulating Factor Are Strong Predictors of First-Time Myocardial Infarction in the General Population

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Alexandru Schiopu ◽  
Eva Bengtsson ◽  
Isabel Goncalves ◽  
Jan Nilsson ◽  
Gunilla Nordin Fredrikson ◽  
...  
Keyword(s):  
Risk Model ◽  
Risk Group ◽  
Intermediate Risk ◽  
Colony Stimulating Factor ◽  
Framingham Risk ◽  
Chemotactic Protein ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
First Time ◽  
Stimulating Factor

Objective: Monocytes/macrophages and neutrophils play important roles in the pathogenesis of cardiovascular disease. We hypothesized that mediators governing myeloid cell homeostasis might help predict the incidence of first-time acute myocardial infarction (AMI). Methods: We included 385 individuals who suffered an AMI during a median follow-up of 15.2 years, and 401 age and sex-matched controls that remained event free, recruited from the Malmö Diet and Cancer Study cohort. The participants had no documented coronary artery disease previous to inclusion. We performed parallel measurements of monocyte chemotactic protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), CCL3, CCL4, CCL20, CXCL1, CXCL16, and CX3CL1 in plasma samples collected at baseline, by using a Proximity Ligation Assay. Results: MCP-1 presented a strong positive correlation (HR (95% CI): 2.07 (1.77-2.43), p<0.001), whereas M-CSF had a strong negative correlation with incident AMI (HR (95% CI): 0.49 (0.41-0.58), p<0.001). These relationships were independent of the classic Framingham risk factors (age, ex, smoking, total cholesterol, HDL, systolic blood pressure), diabetes, CRP, and of the other considered myeloid biomarkers. Addition of MCP-1 and M-CSF significantly improved the predictive ability of a model including the Framingham risk factors alone (c-statistic 0.82 [95% CI 0.78-0.85] with MCP-1 and M-CSF vs. 0.66 [95% CI 0.62-0.70], P<0.05). Addition of MCP-1 and M-CSF to the risk model led to a net reclassification improvement (NRI) of 0.51 (95% CI 0.42-0.60), and an integrated discrimination improvement (IDI) of 0.19 (95% CI 0.16-0.21). The model including MCP-1 and M-CSF was particularly effective in controls, leading to a 65% net re-classification into lower risk categories, and in subjects within the intermediate risk group (10-20%), where 70% of individuals were correctly up or down re-classified. Conclusion: MCP-1 and M-CSF have opposite relationships with the risk for AMI in the general population. Addition of MCP-1 and M-CSF significantly improves the predictive power of the Framingham risk model, leading to correct re-classification of a high percentage of individuals, particularly in the intermediate risk group.

scholarly journals Absence of Colony-Stimulating Factor-1 in Osteopetrotic (csfmoP/csfmOP) Mice Results in Male Fertility Defects1

1996 ◽  
Vol 55 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Paula E. Cohen ◽  
Orin Chisholm ◽  
Robert J. Arceci ◽  
E. Richard Stanley ◽  
Jeffrey W. Pollard
Keyword(s):  
Male Fertility ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

scholarly journals Expression and functionality of the trkA proto-oncogene product/NGF receptor in undifferentiated hematopoietic cells

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1479-1485 ◽  
Author(s):  
S Chevalier ◽  
V Praloran ◽  
C Smith ◽  
D MacGrogan ◽  
NY Ip ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Scatchard Analysis ◽  
Colony Stimulating Factor ◽  
Ngf Receptor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
First Time ◽  
Stimulating Factor ◽  
Hematopoietic Cell Lines

Abstract The expression of the low-affinity NGF receptor (p75) and the trkA proto-oncogene product was analyzed in a series of human hematopoietic cell lines at protein and RNA levels. We did not detect any form of NGF receptor in cell lines displaying a myelomonocytic phenotype (HL60 and U937). In contrast, cells displaying a more immature erythroleukemic phenotype (TF1 and K562) expressed TrkA in the absence of detectable p75. Scatchard analysis showed a single high-affinity site for NGF (kd = 10(-10) mol/L), with a copy number ranging from 300 to 3,000 sites per cell depending on the studied cell line. In addition, NGF induced autophosphorylation of TrkA and could substitute for granulocyte- monocyte colony-stimulating factor to trigger the proliferation of the TF1 cell line, with a half-maximal signal observed at 50 pmol/L, indicating that p75 is not required for DNA synthesis in this cell line. The physiologic relevance of NGF in early hematopoiesis was confirmed by showing that 12% to 15% of progenitor blood cells from mice treated with 5-fluorouracil expressed TrkA and that these cells could be induced to proliferate and differentiate in response to NGF in association with macrophage colony-stimulating factor. Our study demonstrates for the first time that trkA proto-oncogene expression and activation is not restricted to the nervous system, but is also an important element in early hematopoiesis.

scholarly journals Effects of Toxoplasma gondii on Sperm Parameters and Histomorphometry of Testis in Experimentally Infected Rats

2021 ◽  
Vol 16 (2) ◽  
Author(s):  
Monir Taherimoghaddam ◽  
Maryam Bahmanzadeh ◽  
Leili Tapak ◽  
Amir Hossein Maghsood ◽  
Mohammad Fallah ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Reproductive System ◽  
Leydig Cells ◽  
Male Reproductive System ◽  
Sperm Parameters ◽  
Male Rats ◽  
Testis Weight ◽  
Histomorphometric Analysis ◽  
Obligate Intracellular ◽  
Stimulating Factor

Background: Toxoplasma gondii, an obligate intracellular parasite, can be involved in the infection of the male reproductive system. Objectives: Since more than a third of the human population and an increasing number of couples with idiopathic infertility are affected by toxoplasmosis, there is a necessity to evaluate the effects of T. gondii on the reproductive system. Methods: In this experimental study, detailed description of sperm parameters, hormone levels (testosterone, follicular stimulating factor [FSH], and luteinizing hormone [LH]), and histomorphometric analysis were gathered every 10 days on T. gondii infected Wistar male rats until day 80. Data on testis and body weight were also collected. Results: Sperm parameters (motility, viability, count, and normal sperms) as well as LH level were significantly lower in infected rats. No significant decrease was observed in FSH and testosterone levels. The number of Leydig cells significantly decreased on day 20. Significant reduction of Sertoli cells was also detected on day 60. Bodyweight reduced significantly on days 20 and 60, but the testis weight was elevated. Conclusions: T. gondii infection can lead to diminished fertility parameters, but not sterility in rats. The parasite could temporarily interfere with the male reproductive system.

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