ArticlePloS one2015
Loss of vascular endothelial growth factor A (VEGFA) isoforms in granulosa cells using pDmrt-1-Cre or Amhr2-Cre reduces fertility by arresting follicular development and by reducing litter size in female mice.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Comparison of chromatin accessibility remodeling of granulosa cells in patients with endometrioma or pelvic/tubal infertility.Journal of assisted reproduction and genetics · 2025Article
- Unlocking Genetic Mysteries during the Epic Sperm Journey toward Fertilization: Further ExpandingBiomolecules · 2024Review
- Special Staining and Protein Expression of VEGF/EGFR and P53/NF-κB in Cryptorchid Tissue of Erhualian Pigs.Life (Basel, Switzerland) · 2024Article
- Potential biomarkers to predict return to fertility after discontinuation of female contraceptives-looking to the future.Frontiers in reproductive health · 2023Review
- Prenatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters the Expression of miR-122-5p and Its TargetInternational journal of molecular sciences · 2022Article
- In Silico Identification of lncRNAs Regulating Sperm Motility in the Turkey (International journal of molecular sciences · 2022Article
- Cathepsin B Regulates Mice Granulosa Cells' Apoptosis and Proliferation In Vitro.International journal of molecular sciences · 2021Article
- Orexin-A Regulates Follicular Growth, Proliferation, Cell Cycle and Apoptosis in Mouse Primary Granulosa Cells via the AKT/ERK Signaling Pathway.Molecules (Basel, Switzerland) · 2021Article
- The effects of flutamide on the neonatal rat hypothalamic-pituitary-adrenal and gonadal axes in response to hypoxia.Physiological reports · 2019Article
- Comparative analysis of differentially expressed genes between the ovaries from pregnant and nonpregnant goats using RNA-Seq.Journal of biological research (Thessalonike, Greece) · 2019Article
- Hormonal regulation of vascular endothelial growth factor A (VEGFA) gene expression in granulosa and theca cells of cattle1.Journal of animal science · 2019Article
- Ovarian Follicular Theca Cell Recruitment, Differentiation, and Impact on Fertility: 2017 Update.Endocrine reviews · 2018Review
- Regulatory roles of ephrinA5 and its novel signaling pathway in mouse primary granulosa cell apoptosis and proliferation.Cell cycle (Georgetown, Tex.) · 2018Article
- Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice.Biology of reproduction · 2016Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Because VEGFA has been implicated in follicle development, the objective of this study was to determine the effects of granulosa- and germ cell-specific VEGFA loss on ovarian morphogenesis, function, and female fertility. pDmrt1-Cre mice were mated to floxed VEGFA mice to develop granulosa-/germ cell-specific knockouts (pDmrt1-Cre;Vegfa-/-). The time from mating to first parturition was increased when pDmrt1-Cre;Vegfa-/- females were mated to control males (P = 0.0008) and tended to be longer for heterozygous females (P < 0.07). Litter size was reduced for pDmrt1-Cre;Vegfa-/- females (P < 0.007). The time between the first and second parturitions was also increased for heterozygous females (P < 0.04) and tended to be increased for pDmrt1-Cre;Vegfa-/- females (P < 0.07). pDmrt1-Cre;Vegfa-/- females had smaller ovaries (P < 0.04), reduced plasma estradiol (P < 0.007), fewer developing follicles (P < 0.008) and tended to have fewer corpora lutea (P < 0.08). Expression of Igf1r was reduced (P < 0.05); expression of Foxo3a tended to be increased (P < 0.06); and both Fshr (P < 0.1) and Sirt6 tended to be reduced (P < 0.06) in pDmrt1-Cre;Vegfa-/- ovaries. To compare VEGFA knockouts, we generated Amhr2-Cre;Vegfa-/- mice that required more time from mating to first parturition (P < 0.003) with variable ovarian size. Both lines had more apoptotic granulosa cells, and vascular staining did not appear different. Taken together these data indicate that the loss of all VEGFA isoforms in granulosa/germ cells (proangiogenic and antiangiogenic) causes subfertility by arresting follicular development, resulting in reduced ovulation rate and fewer pups per litter.
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