Journal article
VEGFA Family Isoforms Regulate Spermatogonial Stem Cell Homeostasis in Vivo
Endocrinology (Philadelphia), Vol.153(2), pp.887-900
02/01/2012
Handle:
https://hdl.handle.net/2376/116814
PMCID: PMC3275389
PMID: 22147017
Abstract
The objective of the present study was to investigate vascular endothelial growth factor A (VEGFA) isoform regulation of cell fate decisions of spermatogonial stem cells (SSC) in vivo. The expression pattern and cell-specific distribution of VEGF isoforms, receptors, and coreceptors during testis development postnatal d 1–180 suggest a nonvascular function for VEGF regulation of early germ cell homeostasis. Populations of undifferentiated spermatogonia present shortly after birth were positive for VEGF receptor activation as demonstrated by immunohistochemical analysis. Thus, we hypothesized that proangiogenic isoforms of VEGF (VEGFA164) stimulate SSC self-renewal, whereas antiangiogenic isoforms of VEGF (VEGFA165b) induce differentiation of SSC. To test this hypothesis, we used transplantation to assay the stem cell activity of SSC obtained from neonatal mice treated daily from postnatal d 3–5 with 1) vehicle, 2) VEGFA164, 3) VEGFA165b, 4) IgG control, 5) anti-VEGFA164, and 6) anti-VEGFA165b. SSC transplantation analysis demonstrated that VEGFA164 supports self-renewal, whereas VEGFA165b stimulates differentiation of mouse SSC in vivo. Gene expression analysis of SSC-associated factors and morphometric analysis of germ cell populations confirmed the effects of treatment on modulating the biological activity of SSC. These findings indicate a nonvascular role for VEGF in testis development and suggest that a delicate balance between VEGFA164 and VEGFA165b isoforms orchestrates the cell fate decisions of SSC. Future in vivo and in vitro experimentation will focus on elucidating the mechanisms by which VEGFA isoforms regulate SSC homeostasis.
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Details
- Title
- VEGFA Family Isoforms Regulate Spermatogonial Stem Cell Homeostasis in Vivo
- Creators
- Kyle C Caires - Department of Animal Sciences (K.C.C., J.M.d.A., D.J.M.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, Department of Animal Science (K.C.C.), Berry College, Mount Berry, Georgia 30149Jeanene M de Avila - Department of Animal Sciences (K.C.C., J.M.d.A., D.J.M.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164Andrea S Cupp - Department of Animal Sciences (A.S.C.), University of Nebraska-Lincoln, Lincoln, Nebraska 68583Derek J McLean - Department of Animal Sciences (K.C.C., J.M.d.A., D.J.M.), Center for Reproductive Biology, Washington State University, Pullman, Washington 99164
- Publication Details
- Endocrinology (Philadelphia), Vol.153(2), pp.887-900
- Academic Unit
- Center for Reproductive Biology
- Identifiers
- 99900547960201842
- Language
- English
- Resource Type
- Journal article