KDR-LacZ-expressing cells are involved in ovarian and testis-specific vascular development, suggesting a role for VEGFA in the regulation of this vasculature |
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Authors: | Rebecca C Bott Debra T Clopton Anna M Fuller Ryann M McFee Ningxia Lu Renee M McFee Andrea S Cupp |
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Institution: | (1) Department of Animal Science, A224i Animal Science Building, University of Nebraska-Lincoln, 3800 Fair Street, Lincoln, NE 68583-0908, USA; |
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Abstract: | Our objectives were to evaluate kinase insert domain protein receptor (KDR)-β-galactosidase (LacZ) expression as a marker
for vascular development during gonadal morphogenesis and to determine whether any novel non-angiogenic KDR-LacZ expression
was present in mouse testes or ovaries. Gonads were collected from mice expressing LacZ driven by the Kdr promoter (KDR-LacZ) from embryonic day 11 (E11) through postnatal day 60 (P60). At E11.5, mesonephric cells expressing KDR-LacZ
seemed to migrate into the developing testis and surrounded developing seminiferous cords. Cells expressing KDR-LacZ appeared
in the ovary with no apparent migration from the adjacent mesonephros, suggesting a different origin of endothelial cells.
Testis organ cultures from E11 mice were treated with 8 μM VEGFR-TKI, a vascular endothelial growth factor A signal transduction
inhibitor; subsequently, the amount of KDR-LacZ staining was reduced by 66%-99% (P<0.002), and the ability of KDR-expressing cells to form a densely organized vascular network was inhibited. Novel non-angiogenic
KDR-LacZ staining was detected in the testis on specific subsets of germ cells at E16, E17, P4, P20, P30, and P60. In ovaries,
staining was present on oocytes within oocyte cysts at E17 and within late secondary follicles of postnatal mice. Thus, KDR
is an excellent marker for analyzing vascular development in the gonads. Inhibition of VEGFA signal transduction prevents
the development of testis-specific vasculature. Furthermore, non-vascular KDR-LacZ staining suggests that KDR directly affects
both spermatogenesis and somatic-oocyte interactions during gametogenesis. |
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