Single-Cell Transcriptomic Atlas of Primate Ovarian Aging. Wang S et al. (2020) Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders. THis gene is an ovarian endothelial cell marker.//////////////////
Plasma Von Willebrand factor antigen levels are elevated in the classic phenotypes of polycystic ovary syndrome. Koiou E et al. We aimed to assess plasma Von Willebrand factor (vWF) levels in women with polycystic ovary syndrome (PCOS) and to compare these levels among the different PCOS phenotypes.We studied 140 women with PCOS and 40 age and body mass index (BMI)- matched healthy women (control group).
RESULTS:
Plasma vWF antigen levels were higher in women with PCOS than in controls (p=0.017). Plasma vWF antigen levels were also higher in patients with phenotypes 1 [i.e. with anovulation (ANOV), biochemical hyperandrogenemia or clinical manifestations of hyperandrogenemia (HA) and polycystic ovaries (PCO)] and 2 (i.e. with ANOV and HA but without PCO) than in controls (p=0.017). In contrast, plasma vWF antigen levels did not differ between controls and patients with phenotypes 3 (i.e. with HA and PCO but without ANOV) and 4 (i.e. with ANOV and PCO but without HA) or between patients with phenotypes 1 and 2 and patients with phenotypes 3 and 4. When overweight/obese and normal weight subjects were analyzed separately, plasma vWF antigen levels did not differ between patients with PCOS (regardless of phenotype) and controls.
CONCLUSIONS:
Plasma vWF levels are elevated in women with PCOS. This increase appears to be more pronounced in women with phenotypes 1 and 2 of PCOS. Given the association between vWF levels and increased incidence of cardiovascular events, the evaluation of vWF levels in women with PCOS might be helpful for cardiovascular risk stratification, but prospective studies are needed to support this hypothesis.///////////Denis et al. (1998) generated a mouse model for von Willebrand disease by using gene targeting. VWF-deficient mice appeared normal at birth; they were viable and fertile. Neither von Willebrand factor nor VWF-propolypeptide (von Willebrand antigen II) was detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximately 10% of neonates. As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by von Willebrand factor.
NCBI Summary:
This gene encodes a glycoprotein involved in hemostasis. The encoded preproprotein is proteolytically processed following assembly into large multimeric complexes. These complexes function in the adhesion of platelets to sites of vascular injury and the transport of various proteins in the blood. Mutations in this gene result in von Willebrand disease, an inherited bleeding disorder. An unprocessed pseudogene has been found on chromosome 22. [provided by RefSeq, Oct 2015]
General function
Extracellular binding protein
Comment
Cellular localization
Secreted
Comment
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Theca
Comment
Immunolocalization of von Willebrand factor and vascular endothelial growth factor during follicular atresia in the swamp buffalo ovary. Feranil JB 2005 et al.
The aim of this study was to investigate the distribution pattern of von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) in the healthy antral and atretic follicles of Philippine swamp buffaloes (SB) in comparison with Holstein-Friesian cows (HF). Paraffin sections of healthy follicles and atretic follicles at various stages were immunostained with vWF antibody and VEGF antibody. The density of vWF-positive capillary vessels in the theca interna significantly increased as atresia progressed in SB, whereas the density significantly decreased in late atretic follicles compared with advanced ones in HF. On the other hand, the area of vWF-positive capillary vessels in the theca interna significantly increased as atresia progressed in both SB and HF. Immunoreactions of VEGF in the granulosa cells (in all follicle types) were observed in both SB and HF. In the granulosa layer, a reduction in the VEGF immunoreaction was noted as follicles progressed from healthy to advanced atretic follicles in both animals. Granulosa cells (in both SB and HF) showed a higher immunopositive staining than theca cells. In the theca interna, VEGF immunostaining diminished as follicles progressed to the late atretic follicles in both animals. These results indicate that during atresia, changes of vWF expression are the opposite of VEGF expression in SB. Both vWF and VEGF are suggested to be associated with follicular atresia in SB.
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Follicle stages
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: human
Mutation name: None
type: naturally occurring fertility: fertile Comment: Conservative management of massive hematoperitoneum caused by ovulation in a patient with severe form of von Willebrand disease--a case report. Terzic M et al. Von Willebrand disease (VWD) is the most common inherited bleeding condition that involves extended or excessive bleeding, caused by the deficiency or defect of von Willebrand factor (VWF). Hematoperitoneum as a complication of gynecologic diseases represents acute condition which is usually caused by the hemorrhagic corpus luteum or a rupture of either ectopic pregnancy or a hemorrhagic ovarian cyst. The authors present a unique case of conservatively managed massive hematoperitoneum caused by ovulation in a patient with severe form of von Willebrand disease who had right adnexectomy due to hemorrhagic corpus luteum four months prior. This conservative management by blood product and factor concentrate support could be a method of choice in selected hemodynamically stable patients. Furthermore, recurrent bleeding episodes following ovulation could be prevented by suppression of ovulation using oral contraceptive pills.
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: Denis et al. (1998) generated a mouse model for von Willebrand disease by using gene targeting. VWF-deficient mice appeared normal at birth; they were viable and fertile. Neither von Willebrand factor nor VWF-propolypeptide (von Willebrand antigen II) was detectable in plasma, platelets, or endothelial cells of the homozygous mutant mice. The mutant mice exhibited defects in hemostasis with a highly prolonged bleeding time and spontaneous bleeding events in approximately 10% of neonates. As in the human disease, the factor VIII level in these mice was reduced strongly as a result of the lack of protection provided by von Willebrand factor.