Vascular endothelial growth factor regulates germ cell survival during establishment of spermatogenesis in the bovine testis

Abstract

Vascular endothelial growth factor-A (VEGFA) is a hypoxia-inducible peptide essential for angiogenesis and targets nonvascular cells in a variety of tissues and cell types. The objective of the current study was to determine the function of VEGF during testis development in bulls. We used an explant tissue culture and treatment approach to test the hypothesis that VEGFA-164 could regulate the biological activity of bovine germ cells. We demonstrate that VEGFA, KDR, and FLT1 proteins are expressed in germ and somatic cells in the bovine testis. Treatment of bovine testis tissue with VEGFA in vitro resulted in significantly more germ cells following 5 days of culture when compared with controls. Quantitative real-time RT-PCR analysis determined that VEGF treatment stimulated an intracellular response that prevents germ cell death in bovine testis tissue explants, as indicated by increased expression of BCL2 relative to BAX and decreased expression of BNIP3 at 3, 6, and 24 h during culture. Blocking VEGF activity in vitro using antisera against KDR and VEGF significantly reduced the number of germ cells in VEGF-treated testis tissue to control levels at 120 h. Testis grafting provided in vivo evidence that bovine testis tissue treated with VEGFA for 5 days in culture contained significantly more differentiating germ cells compared with controls. These findings support the conclusion that VEGF supports germ cell survival and sperm production in bulls.

Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary

“…As VEGF reduces leukocyte recruitment, PRP may ameliorate the free radical damage caused by leukocytes in ischemic tissue [27]. In addition, VEGF stimulated anti-apoptotic factor B cell leukemia/lymphoma 2 mRNA expression to promote germ cell survival [28]. In the current study, the significant increase in VEGF together with the reduction in OSI and histological sequelae of tissue damage suggests that VEGF is a promising endogenous protective factor against ovarian I/R damage [28] and that augmentation of local VEGF can promote tissue preservation.…”

“…The active secretion of growth factors by platelets is known to begin within 10 min of activation by calcium, and ultimately more than 95% of the presynthesized growth factors are secreted within 1 h [28]. EGF, TGFα and heparin binding EGF directly bind to and activate EGFRs [31], leading to induction of downstream signaling cascades (i.e., Akt signaling) that promote survival against ischemia [32].…”

Maintaining the male germline: regulation of spermatogonial stem cells

“…Treating testis tissue from 4-to 8-week calves that contain spermatogonia as the only germ cell with VEGF resulted in an increase in spermatogonia compared to controls treated with vehicle (Caires et al 2009). VEGF induces the expression of genes that promote germ cell survival in the testis tissue (Caires et al 2009), suggesting that one nonvascular role of VEGF signaling in the testis is promoting spermatogonial survival during testis development. Thus, the interaction between GDNF and VEGF may promote general cell survival in SSCs as well as undifferentiated spermatogonia.…”

Selenium Increases Testicular Steroidogenesis and Growth Factors Expression in Streptozotocin-induced Diabetic Rats

“…VEGF is important for spermatogenesis and its receptors were found located on interstitial cells and seminiferous tubules [19] . VEGF supports proliferation of germ cells and inhibits its apoptosis [20] . In addition, VEGF facilitates the transport of endocrine hormones, nutrition and oxygen, regulates microcirculation and modulates endothelial permeability in testis [21,22] .…”