Gene injections of vascular endothelial growth factor and growth differentiation factor-9 stimulate ovarian follicular development in immature female rats

2008 ◽  
Vol 89 (5) ◽  
pp. 1563-1570 ◽  
Author(s):  
Takashi Shimizu ◽  
Koji Iijima ◽  
Yoshinori Ogawa ◽  
Hitoshi Miyazaki ◽  
Hiroshi Sasada ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Follicular Development ◽  
Female Rats ◽  
Vascular Endothelial ◽  
Immature Female ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 9 ◽  
Ovarian Follicular Development ◽  
Endothelial Growth Factor

scholarly journals Effect of direct ovarian injection of vascular endothelial growth factor gene fragments on follicular development in immature female rats

Reproduction ◽  
2007 ◽  
Vol 134 (5) ◽  
pp. 677-682 ◽  
Author(s):  
Takashi Shimizu ◽  
Koji Iijima ◽  
Kanako Miyabayashi ◽  
Yoshinori Ogawa ◽  
Hitoshi Miyazaki ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Follicular Development ◽  
Female Rats ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Immature Female ◽  
Rat Ovary ◽  
Ovulatory Follicles ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) expression in granulosa cells is associated with the thecal vasculature growth during ovarian follicular development. We hypothesized that injection of VEGF gene fragments directly into the rat ovary would induce production of a large number of ovulatory follicles and that these follicles would ovulate. To test this hypothesis, we treated immature female rats with combinations of hormones and VEGF gene fragments. The animals were divided into two groups: one group received solution containing transfection reagents as a control (n= 5), while the other group received direct ovarian injection of VEGF gene fragments at 19 (n= 5), 21 (n= 5), 23 (n= 5), or 25 (n= 5) days after birth followed by i.p. administration of 20 IU equine chorionic gonadotropin (eCG) at the age of 26 days. Forty-eight hours after eCG injection, animals were given 20 IU human chorionic gonadotropin (hCG) i.p. and then the oocytes in both groups were counted. The maximum number of ovulated oocytes was obtained when the VEGF gene fragments were injected into the rat ovary at 21 days after birth. Histological examination revealed that the injection of VEGF gene fragments markedly increased the vascular density around the preovulatory follicles and also the number of these follicles. Our data provide the first reported evidence that most ovulatory follicles generated by injection of VEGF gene fragments are able to ovulate upon hCG treatment. These results demonstrate that injection of VEGF gene fragments directly into the ovary stimulates the development of antral follicles by inducing the formation of thecal vasculature in immature female rats.

scholarly journals Estrogen Receptor-α Overexpression Suppresses 17β-Estradiol-Mediated Vascular Endothelial Growth Factor Expression and Activation of Survival Kinases

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3881-3889 ◽  
Author(s):  
Shameena Bake ◽  
Lijiang Ma ◽  
Farida Sohrabji
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Estrogen Receptor ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Line ◽  
Female Rats ◽  
High Dose ◽  
Vascular Endothelial ◽  
17Β Estradiol ◽  
Endothelial Growth Factor

Estrogen and its receptors influence growth and differentiation by stimulating the production and secretion of growth factors. Our previous studies indicate an increased expression of estrogen receptor (ER)-α and decreased growth factor synthesis in the olfactory bulb of reproductive senescent female rats as compared with young animals. The present study tests the hypothesis that abnormal overexpression of ERα contributes to decreased growth factor synthesis. We developed the HeLa-Tet-On cell line stably transfected with ERα (HTERα) that expresses increasing amounts of ERα with increasing doses of doxycycline (Dox). Increasing doses of Dox had no effect on vascular endothelial growth factor (VEGF) secretion in HTERα cells. However, in the presence of 40 nm 17β-estradiol, VEGF secretion increased in low-dose Dox-exposed HTERα cultures, which was attenuated by the ERα antagonist, 1,3-Bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]1H-pyrazole dihydrochloride. However, at high-dose Dox and, consequently, high ERα levels, estradiol failed to increase VEGF. In the HeLa X6 cell line in which the Tet-On construct is upstream of an unrelated gene (Pitx2A), estradiol failed to induce VEGF at any Dox dose. Furthermore, in the HTERα cell line, estradiol selectively down-regulates phospho-ERK2 and phospho-Akt at high ERα expression. This study clearly demonstrates that the dose of receptor critically mediates estradiol’s ability to regulate growth factors and survival kinases. The present data also support the hypothesis that 17β-estradiol treatment to an ERα overexpressing system, such as the senescent brain, could reverse the normally observed beneficial effect of estrogen.

Direct injection of vascular endothelial growth factor into the ovary of mice promotes follicular development

2004 ◽  
Vol 82 ◽  
pp. 1101-1105 ◽  
Author(s):  
Ramiro Quintana ◽  
Laura Kopcow ◽  
Carlos Sueldo ◽  
Guillermo Marconi ◽  
Nidia Gomez Rueda ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Direct Injection ◽  
Follicular Development ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

scholarly journals Estrogen Deprivation and Replacement Modulate Cerebral Capillary Density with Vascular Expression of Angiogenic Molecules in Middle-Aged Female Rats

2003 ◽  
Vol 23 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Subrina Jesmin ◽  
Yuichi Hattori ◽  
Ichiro Sakuma ◽  
Ming-Yue Liu ◽  
Chishimba N. Mowa ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Capillary Density ◽  
Cerebral Vessels ◽  
Female Rats ◽  
Sham Operation ◽  
Vascular Endothelial ◽  
Middle Aged ◽  
Cerebral Capillary ◽  
Endothelial Growth Factor

The effect of postmenopausal estrogen replacement therapy (ERT) on the risk or severity of cerebrovascular disorders is as yet unclear, and the evidence for flow preservation being a mechanism of estrogen neuroprotection remains elusive. The authors examined whether estrogen-mediated flow-preserving neuroprotective mechanisms, if any, may involve its angiogenic action. This study was conducted using middle-aged (44 weeks) female rats because of the importance of aging in cerebrovascular disease in women. Middle-aged female rats were subjected to sham operation, ovariectomy, or ovariectomy with ERT. The anatomic cerebral capillary morphology showed a significant reduction in the total capillary density in the frontal cortex after ovariectomy. This was associated with marked decreases in protein and gene expression of vascular endothelial growth factor and its angiogenic receptors in cerebral vessels, as demonstrated by immunohistochemistry and in situ hybridization. The expression levels of both estrogen receptor (ER) subtypes, ERα and ERβ, in cerebral vessels were significantly reduced after ovariectomy, but ERβ was more dramatically downregulated as assessed by the ERβ/ERα ratio. These ovariectomy-induced changes were completely prevented by ERT. Vascular endothelial growth factor appears to be a critical regulatory molecule for physiologic cerebral angiogenesis in middle-aged female rats and may play an important role in the flow-preserving neuroprotective action of estrogen through its angiogenic and antiapoptotic properties.

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