ArticleBiology of reproduction2006
Vascular endothelial growth factor and kinase domain region receptor are involved in both seminiferous cord formation and vascular development during testis morphogenesis in the rat.
Article in Biology of reproduction, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 107 citations in OpenAlex.
- Long-term culture and significant expansion of human Sertoli cells whilst maintaining stable global phenotype and AKT and SMAD1/5 activation.Cell communication and signaling : CCS · 2015Trial
- Article
- Defects in the H3t Gene Cause an Increase in Leydig Cells With Impaired Spermatogenesis in Mice.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- VEGF-dependent testicular vascularisation involves MEK1/2 signalling and the essential angiogenesis factors, SOX7 and SOX17.BMC biology · 2024Article
- Microenvironment of spermatogonial stem cells: a key factor in the regulation of spermatogenesis.Stem cell research & therapy · 2024Review
- Fetal Leydig cells: What we know and what we don't.Molecular reproduction and development · 2024Review
- Molecular mechanisms of cellular dysfunction in testes from men with non-obstructive azoospermia.Nature reviews. Urology · 2024Review
- A role for TRPC3 in mammalian testis development.Frontiers in cell and developmental biology · 2024Article
- Defining the cellular complexity of the zebrafish bipotential gonad.Biology of reproduction · 2023Article
- In Silico Analysis of miRNA-Mediated Genes in the Regulation of Dog Testes Development from Immature to Adult Form.Animals : an open access journal from MDPI · 2023Article
- Article
- Using a testis regeneration model, FGF9, LIF, and SCF improve testis cord formation while RA enhances gonocyte survival.Cell and tissue research · 2022Article
- The Fate of Leydig Cells in Men with Spermatogenic Failure.Life (Basel, Switzerland) · 2022Review
- Testicular torsion: its effect on autoimmunisation, pituitary-testis axis and correlation with primary gonadal dysfunction in boys.Pediatric research · 2021Article
- Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis†.Biology of reproduction · 2021Article
- Heterogeneity and Dynamics of Vasculature in the Endocrine System During Aging and Disease.Frontiers in physiology · 2021Review
- Review
- Article
- A perivascular niche for multipotent progenitors in the fetal testis.Nature communications · 2018Article
- Transcriptomic analysis of male and female Schistosoma mekongi adult worms.Parasites & vectors · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Morphological male sex determination is dependent on migration of endothelial and preperitubular cells from the adjacent mesonephros into the developing testis. Our hypothesis is that VEGFA and its receptor KDR are necessary for both testicular cord formation and neovascularization. The Vegfa gene has 8 exons with many splice variants. Vegfa120, Vegfa164, and Vegfa188 mRNA isoforms were detected on Embryonic Day (E) 13.5 (plug date=E0) in the rat. Vegfa120, Vegfa144, Vegfa164, Vegfa188, and Vegfa205 mRNA were detected at E18 and Postnatal Day 3 (P3). Kdr mRNA was present on E13.5, whereas Fms-like tyrosine kinase 1 receptor (Flt1) mRNA was not detected until E18. VEGFA protein was localized to Sertoli cells at cord formation and KDR to germ and interstitial cells. The VEGFA signaling inhibitors SU1498 (40 microM) and VEGFR-TKI (8 microM) inhibited cord formation in E13 testis cultures with 90% reduced vascular density (P<0.01) in VEGFR-TKI-treated organs. Furthermore, Je-11 (10 microM), an antagonist to VEGFA, also perturbed cord formation and inhibited vascular density by more than 50% (P<0.01). To determine signal transduction pathways involved in VEGFA's regulation of testis morphogenesis, E13 testis were treated with LY 294002 (15 microM), a phosphoinositide 3-kinase (PI3K) pathway inhibitor, resulting in inhibition of both vascular density (46%) and cord formation. Thus, we support our hypothesis and conclude that VEGFA, secreted by the Sertoli cell, is involved in both neovascularization and cord formation and potentially acts through the PI3K pathway during testis morphogenesis to elicit its effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.