Expression of granulocyte–macrophage colony stimulating factor (GM-CSF) in male germ cells: GM-CSF enhances sperm motility

Vilanova, L. T.; Rauch, M.; Mansilla, Alejandra; Zambrano, Ángara; Brito, Mónica; Werner, E; Alfaro, Verónica; Cox, J.F.; Concha, Ilona I.

doi:10.1016/s0093-691x(03)00106-7

Cited by 21 publications

(22 citation statements)

References 31 publications

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“…However, the biological role of GM-CSF has recently been associated to glucose transport in several non-hematopoietic cells including the spermatozoa [41]. GM-CSF increased glucose uptake via functional facilitative hexose transporters GLUT improving the freezing/thawing resistance and subsequent linear motility [12,41]. These finding, together with observations that GM-CSF and both subunits of the GM-CSF receptor are expressed in bovine oocytes and granulosa cells, suggest that GM-CSF may activate cumulus expansion and oocyte maturation, enhancing subsequent embryonic development.…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances cumulus cell expansion in bovine oocytes

Peralta

Bucher

Fernández

et al. 2013

Reprod Biol Endocrinol

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BackgroundThe objectives of the study were to characterize the expression of the α- and β-subunits of granulocyte-macrophage colony stimulating factor (GM-CSF) receptor in bovine cumulus cells and oocytes and to determine the effect of exogenous GM-CSF on cumulus cells expansion, oocyte maturation, IGF-2 transcript expression and subsequent competence for embryonic development.MethodsCumulus-oocyte complexes (COC) were obtained by aspirating follicles 3- to 8-mm in diameter with an 18 G needle connected to a vacuum pump at −50 mmHg. Samples of cumulus cells and oocytes were used to detect GM- CSF receptor by immunofluorescence. A dose–response experiment was performed to estimate the effect of GM-CSF on cumulus cell expansion and nuclear/cytoplasmic maturation. Also, the effect of GM-CSF on IGF-2 expression was evaluated in oocytes and cumulus cells after in vitro maturation by Q-PCR. Finally, a batch of COC was randomly assigned to in vitro maturation media consisting of: 1) synthetic oviductal fluid (SOF, n = 212); 2) synthetic oviductal fluid supplemented with 100 ng/ml of GM-CSF (SOF + GM-CSF, n = 224) or 3) tissue culture medium (TCM 199, n = 216) and then subsequently in vitro fertilized and cultured for 9 days.ResultsImmunoreactivity for both α and β GM-CSF receptors was localized in the cytoplasm of both cumulus cells and oocytes. Oocytes in vitro matured either with 10 or 100 ng/ml of GM-CSF presented a higher (P < 0.05) cumulus cells expansion than that of the control group (0 ng/ml of GM-CSF). GM-CSF did not affect the proportion of oocytes in metaphase II, cortical granules dispersion and IGF-2 expression. COC exposed to 100 ng/ml of GM-CSF during maturation did not display significant differences in terms of embryo cleavage rate (50.4% vs. 57.5%), blastocyst development at day 7 (31.9% vs. 28.7%) and at day 9 (17.4% vs. 17.9%) compared to untreated control (SOF alone, P = 0.2).ConclusionsGM-CSF enhanced cumulus cell expansion of in vitro matured bovine COC. However, GM-CSF did not increase oocyte nuclear or cytoplasmic maturation rates, IGF-2 expression or subsequent embryonic development.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances cumulus cell expansion in bovine oocytes

Peralta

Bucher

Fernández

et al. 2013

Reprod Biol Endocrinol

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“…They are expressed in hematopoietic cells as well in several non-hematopoietic cell types [Morstyn and Burgess, 1988;Farrar et al, 1989;Nicola, 1989;Zambrano et al, 2001;Vilanova et al, 2003;Rauch et al, 2004], and in both hematopoietic and non-hematopoietic cells, it has been suggested that they have an important role in cell survival [Kamegai et al, 1990;Zambrano et al, 2007].…”

Section: Discussionmentioning

confidence: 99%

“…IL-3 receptor is expressed in male germ cells, mouse testicular Leydig cells, the central cholinergic neurons, and in both the hippocampus and cerebral cortex [Tabira et al, 1998;Rauch et al, 2004;Zambrano et al, 2007]. Also, GM-CSF receptor is expressed in placental trophoblasts, endothelial cells, oligodendrocytes, neurons in the central and peripheral nervous system and male germ cells [Bussolino et al, 1989;Gearing et al, 1989;Baldwin et al, 1993;Vilanova et al, 2003;Rodriguez-Gil et al, 2007], and some tumors [Spielholz et al, 1995;Rivas et al, 1998]. However, it is important to clarify if these receptors have similar mechanisms to insulin increasing glucose uptake or other nutrients such as vitamin C, relevant in cell metabolism and survival.…”

Section: Discussionmentioning

confidence: 99%

Cytokine Stimulation Promotes Increased Glucose Uptake Via Translocation at the Plasma Membrane of GLUT1 in HEK293 Cells

Zambrano

Jara

Murgas

et al. 2010

J of Cellular Biochemistry

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Interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are two of the best-characterized cell survival factors in hematopoietic cells; these factors induce an increase in Akt activity in multiple cell lines, a process thought to be involved in cellular survival. It is known that growth factors require sustained glucose metabolism to promote cell survival. It has been determined that IL-3 and GM-CSF signal for increased glucose uptake in hematopoietic cells. Interestingly, receptors for IL-3 and GM-CSF are present in several non-hematopoietic cell types but their roles in these cells have been poorly described. In this study, we demonstrated the expression of IL-3 and GM-CSF receptors in HEK293 cells and analyzed their effect on glucose uptake. In these cells, both IL-3 and GM-CSF, increased glucose uptake. The results indicated that this increase involves the subcellular redistribution of GLUT1, affecting glucose transporter levels at the cell surface in HEK293 cells. Also the data directly demonstrates that the PI 3-kinase/Akt pathway is an important mediator of this process. Altogether these results show a role for non-insulin growth factors in the regulation of GLUT1 trafficking that has not yet been directly determined in non-hematopoietic cells.

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“…The role of the ligand CSF1 and its receptor Csf1r on the SSCs has not yet been studied. However, there is evidence for the role of the granulocyte macrophage colony-stimulating factor (GM-CSF, official symbol CSF2) in the testis; our group has previously reported that CSF2 enhances the survival of porcine type A spermatogonia [41], and others have demonstrated the expression of CSF2 in male porcine differentiated germ cells [42]. CSF1 acts through the CSF1R receptor, encoded by the c-fms proto-oncogene, which has been shown to be transcriptionally active in both hematopoietic and nonhematopoietic tissues, such as placental trophoblasts, endothelial cells, oligodendrocytes of the central nervous system, follicular fluid, ovarian cells, and fallopian tube cells.…”

Section: Restmentioning

confidence: 99%

The Molecular Signature of Spermatogonial Stem/Progenitor Cells in the 6-Day-Old Mouse Testis1

Kokkinaki

Lee

et al. 2009

Biology of Reproduction

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To characterize the molecular phenotype of spermatogonial stem cells (SSCs), we examined genes that are differentially expressed in the stem/progenitor spermatogonia compared to nonstem spermatogonia. We isolated type A spermatogonia (stem and nonstem type A) from 6-day-old mice using sedimentation velocity at unit gravity and further selected the stem/progenitor cell subpopulation by magnetic activated cell sorting with an antibody to GDNF-receptor-alpha-1 (GFRA1). It has been previously shown that GFRA1 is expressed in SSCs and is required for their stemness. The purity of the isolated cells was approximately 95% to 99% as indicated by immunocytochemistry using anti-GFRA1. Comparison of GFRA1-positive and GFRA1-negative spermatogonia by microarray analysis revealed 99 known genes and 12 uncharacterized transcripts that are overexpressed in the former cell population with a >2-fold change. Interestingly, the highest level of overexpression was observed for Csf1r, encoding the receptor for macrophage colony-stimulating factor (M-CSF, official symbol CSF1), which has a well-established role in the regulation of myeloid progenitor cells. Analysis of our microarray data with a bioinformatics software program (Ingenuity Systems) revealed the potential role of various signaling pathways in stem/progenitor spermatogonia and suggested a common pathway for GFRA1 and CSF1R that may lead to their proliferation. Further investigation to test this hypothesis has shown that CSF1 promotes cell proliferation in primary cultures of the isolated type A spermatogonia and in the spermatogonial-derived stem cell line C18-4. Semiquantitative RT-PCR and immunohistochemistry confirmed the previously mentioned microarray data. Collectively, this study provides novel molecular signatures for stem/progenitor spermatogonia and demonstrates a role for CSF1/CSF1R signaling in regulating their proliferation.

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Expression of granulocyte–macrophage colony stimulating factor (GM-CSF) in male germ cells: GM-CSF enhances sperm motility

Cited by 21 publications

References 31 publications

Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances cumulus cell expansion in bovine oocytes

Granulocyte-macrophage colony stimulating factor (GM-CSF) enhances cumulus cell expansion in bovine oocytes

Cytokine Stimulation Promotes Increased Glucose Uptake Via Translocation at the Plasma Membrane of GLUT1 in HEK293 Cells

The Molecular Signature of Spermatogonial Stem/Progenitor Cells in the 6-Day-Old Mouse Testis1

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