Involvement of fibroblast growth factor 2 (FGF2) and its receptors in the regulation of mouse sperm physiology

Fibroblast growth factor 2 (FGF2) and its receptors (FGFRs) have been described in several tissues, where they regulate cellular proliferation, differentiation, motility and apoptosis. Although FGF2/FGFRs expression in the male reproductive tract has been reported, there is scarce evidence on their presence in the female reproductive tract and their involvement in the modulation of sperm function. Therefore, the objective of this study was to determine the expression of FGF2 in the female reproductive tract and to assess the role of the FGF2/FGFRs system in the regulation of sperm physiology using the murine model. FGF2 was detected in uterus and oviduct protein extracts, and it was immunolocalized in epithelial cells of the uterus,isthmusandampulla, as well as in thecumulus oophorus-oocyte complex. The receptors FGFR1, FGFR2, FGFR3 and FGFR4 were immunodetected in the flagellum and acrosomal region of sperm recovered from thecaudaepididymis. Analysis of testis sections showed the expression of FGFRs in germ cells at different stages of the spermatogenesis, suggesting the testicular origin of the sperm FGFRs. Sperm incubation with recombinant FGF2 (rFGF2) led to increased sperm motility and velocity and to enhanced intracellular Ca2+levels and acrosomal loss compared to the control. In conclusion, this study shows that FGF2 is expressed in tissues of the female reproductive tract. Also, the fact that functional FGFRs are present in mouse sperm and that rFGF2 affects sperm motility and acrosomal exocytosis, suggests the involvement of this system in thein vivoregulation of sperm function.

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Fibroblast growth factor 2 (FGF2) is present in human spermatozoa and is related with sperm motility. The use of recombinant FGF2 to improve motile sperm recovery

Andrology ◽

10.1111/andr.12398 ◽

2017 ◽

Vol 5 (5) ◽

pp. 990-998 ◽

Cited By ~ 5

Author(s):

D. J. Garbarino Azúa ◽

L. Saucedo ◽

S. Giordana ◽

M. L. Magri ◽

M. G. Buffone ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Sperm Motility ◽

Human Spermatozoa ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Motile Sperm ◽

Sperm Recovery

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SOCS-3 antagonises the proliferative and migratory effects of fibroblast growth factor-2 in prostate cancer by inhibition of p44/p42 MAPK signalling

Endocrine Related Cancer ◽

10.1677/erc-10-0007 ◽

2010 ◽

Vol 17 (2) ◽

pp. 525-538 ◽

Cited By ~ 23

Author(s):

Martin Puhr ◽

Frédéric R Santer ◽

Hannes Neuwirt ◽

Gemma Marcias ◽

Alfred Hobisch ◽

...

Keyword(s):

Prostate Cancer ◽

Growth Factor ◽

Cancer Cells ◽

Fibroblast Growth Factor ◽

Cellular Proliferation ◽

Mapk Pathway ◽

Fibroblast Growth Factor 2 ◽

Fibroblast Growth ◽

Prostate Cancer Cells ◽

Stat3 Phosphorylation

Fibroblast growth factor-2 (FGF-2) is highly expressed in prostate cancer. It promotes tumour progression through multiple pathways including those of signal transducers and activators of transcription factor 3 (STAT3), mitogen-activated protein kinases (MAPKs) and Akt. In previous studies, we have reported that STAT3 phosphorylation inversely correlates with suppressor of cytokine signalling-3 (SOCS-3) expression in prostate cancer cells. Recently, it has become evident that SOCS-3-negative regulation is not only limited to the interleukin-6 (IL-6) receptor. We hypothesised that SOCS-3 interferes with FGF signalling, thus influencing the outcome of its action in prostate cancer cells. For this purpose, we treated DU-145 and LNCaP-IL-6+ cells with increasing concentrations of FGF-2, and verified protein phosphorylation. In the presence of FGF-2, neither STAT3, STAT1, nor Akt could be phosphorylated. Solely the p44/p42 MAPK pathway was activated after FGF-2 stimulation. We show for the first time that SOCS-3 interferes with the FGF-2 signalling pathway by modulating p44 and p42 phosphorylation in prostate cancer cells. Decreased SOCS-3 protein expression results in increased MAPK phosphorylation, whereas SOCS-3 overexpression leads to a decreased cellular proliferation and migration. On the basis of the present results, we propose that SOCS-3 is a novel modulator of FGF-2-regulated cellular events in prostate cancer.

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Prolotherapy agent P2G is associated with upregulation of fibroblast growth factor-2 genetic expression in vitro

Journal of Experimental Orthopaedics ◽

10.1186/s40634-020-00312-z ◽

2020 ◽

Vol 7 (1) ◽

Cited By ~ 1

Author(s):

Elisha Johnston ◽

Chandrakanth Emani ◽

Andrew Kochan ◽

Kidane Ghebrehawariat ◽

John Tyburski ◽

...

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Cellular Response ◽

Cellular Proliferation ◽

Science Studies ◽

Cartilage Regeneration ◽

Fibroblast Growth Factor 2 ◽

Independent Effect ◽

Fibroblast Growth

Abstract Purpose Osteoarthritis (OA) is a prevalent, progressively degenerative disease. Researchers have rigorously documented clinical improvement in participants receiving prolotherapy for OA. The mechanism of action is unknown; therefore, basic science studies are required. One hypothesized mechanism is that prolotherapy stimulates tissue proliferation, including that of cartilage. Accordingly, this in vitro study examines whether the prolotherapy agent phenol-glycerin-glucose (P2G) is associated with upregulation of proliferation-enhancing cytokines, primarily fibroblast growth factor-2 (FGF-2). Methods Murine MC3T3-E1 cells were cultured in a nonconfluent state to retain an undifferentiated osteochondroprogenic status. A limitation of MC3T3-E1 cells is that they do not fully reproduce primary human chondrocyte phenotypes; however, they are useful for modeling cartilage regeneration in vitro due to their greater phenotypic stability than primary cells. Two experiments were conducted: one in duplicate and one in triplicate. Treatment consisted of phenol-glycerin-glucose (P2G, final concentration of 1.5%). The results were assessed by quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) to detect mRNA expression of the FGF-2, IGF-1, CCND-1 (Cyclin-D), TGF-β1, AKT, STAT1, and BMP2 genes. Results P2G - treated preosteoblasts expressed higher levels of FGF-2 than water controls (hour 24, p < 0.001; hour 30, p < 0.05; hour 38, p < 0.01). Additionally, CCND-1 upregulation was observed (p < 0.05), possibly as a cellular response to FGF-2 upregulation. Conclusions The prolotherapy agent P2G appears to be associated with upregulation of the cartilage cell proliferation enhancer cytokine FGF-2, suggesting an independent effect of P2G consistent with clinical evidence. Further study investigating the effect of prolotherapy agents on cellular proliferation and cartilage regeneration is warranted.

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The fibroblast growth factor 8 family in the female reproductive tract

Reproduction ◽

10.1530/rep-17-0542 ◽

2018 ◽

Vol 155 (1) ◽

pp. R53-R62 ◽

Cited By ~ 4

Author(s):

Anthony Estienne ◽

Christopher A Price

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Reproductive Tract ◽

Ovarian Follicle ◽

Cumulus Cells ◽

Cell Types ◽

Female Reproductive Tract ◽

Fibroblast Growth ◽

Aberrant Expression ◽

Fibroblast Growth Factor 8

Several growth factor families have been shown to be involved in the function of the female reproductive tract. One subfamily of the fibroblast growth factor (FGF) superfamily, namely the FGF8 subfamily (including FGF17 and FGF18), has become important as Fgf8 has been described as an oocyte-derived factor essential for glycolysis in mouse cumulus cells and aberrant expression ofFGF18has been described in ovarian and endometrial cancers. In this review, we describe the pattern of expression of these factors in normal ovaries and uteri in rodents, ruminants and humans, as well as the expression of their receptors and intracellular negative feedback regulators. Expression of these molecules in gynaecological cancers is also reviewed. The role of FGF8 and FGF18 in ovarian and uterine function is described, and potential differences between rodents and ruminants have been highlighted especially with respect to FGF18 signalling within the ovarian follicle. Finally, we identify major questions about the reproductive biology of FGFs that remain to be answered, including (1) the physiological concentrations within the ovary and uterus, (2) which cell types within the endometrial stroma and theca layer express FGFs and (3) which receptors are activated by FGF8 subfamily members in reproductive tissues.

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Molecular and Clinical Significance of Fibroblast Growth Factor 2 in Development and Regeneration of the Auditory System

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.757441 ◽

2021 ◽

Vol 14 ◽

Author(s):

Minjin Jeong ◽

Katarina Bojkovic ◽

Varun Sagi ◽

Konstantina M. Stankovic

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Auditory System ◽

Therapeutic Agent ◽

Cellular Proliferation ◽

Fibroblast Growth Factor 2 ◽

Biological Processes ◽

Fibroblast Growth ◽

Inner Ear Development

The fibroblast growth factor 2 (FGF2) is a member of the FGF family which is involved in key biological processes including development, cellular proliferation, wound healing, and angiogenesis. Although the utility of the FGF family as therapeutic agents has attracted attention, and FGF2 has been studied in several clinical contexts, there remains an incomplete understanding of the molecular and clinical function of FGF2 in the auditory system. In this review, we highlight the role of FGF2 in inner ear development and hearing protection and present relevant clinical studies for tympanic membrane (TM) repair. We conclude by discussing the future implications of FGF2 as a potential therapeutic agent.

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