Intraovarian actions of anti-angiogenic agents disrupt periovulatory events during the menstrual cycle in monkeys

Xu, Fan; Hazzard, Timothy; Evans, Alice; Charnock-Jones, D. Stephen; Smith, Stephen K.; Stouffer, Richard L.

doi:10.1016/j.contraception.2004.12.017

Cited by 42 publications

(30 citation statements)

References 44 publications

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“…Zimmermann et al (5) have demonstrated that VEGFA blockage alters follicular development and hormone secretion in mice. In monkeys, inhibition of VEGFA impairs oocyte release, steroid production, and the subsequent development of the CL (7,27). However, the VEGFA signal transduction mechanism implicated in follicular cell function has not been identified yet.…”

Section: Figurementioning

confidence: 93%

Intrabursal injection of vascular endothelial growth factor trap in eCG-treated prepubertal rats inhibits proliferation and increases apoptosis of follicular cells involving the PI3K/AKT signaling pathway

Abramovich

Irusta

Parborell

et al. 2010

Fertility and Sterility

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Section: Figurementioning

confidence: 93%

Intrabursal injection of vascular endothelial growth factor trap in eCG-treated prepubertal rats inhibits proliferation and increases apoptosis of follicular cells involving the PI3K/AKT signaling pathway

Abramovich

Irusta

Parborell

et al. 2010

Fertility and Sterility

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“…Direct evidence for the role of angiopoietins in the ovary comes from observations in rhesus monkeys (Xu et al 2005) and rats (Parborell et al 2008). Xu et al (2005) have demonstrated that local injection of ANGPT2 into the POF is able to block ovulation, while the same dose of ANGPT1 is not. It has been proposed that ANGPT2 inhibits the action of ANGPT1 at the level of their common receptor and that the correct balance between these factors is essential for maintaining the integrity of the POF.…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal analysis of the protein expression of angiogenic factors and their related receptors during folliculogenesis in rats with and without hormonal treatment

Abramovich¹,

Celin²,

Hernandez³

et al. 2009

Reproduction

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This study investigated the protein expression and cellular localization of ANGPT1, ANGPT2, and their receptor TEK, as well as vascular endothelial growth factor A (VEGFA) and its receptor KDR (VEGFR2) during folliculogenesis. To obtain follicles at different stages for immunochemistry and western analyses, we used prepubertal untreated, diethylstilbestrol-and equine chorionic gonadotropin-treated rats. To confirm that these hormonal treatments reflect physiological change, we used non-treated adult rats. No expression of ANGPT1 was observed in granulosa cells (Gc) from immature hormone-treated and non-treated rats at any follicular stage. By contrast, ANGPT1 expression in theca cells (Tc) increased with follicular maturation. ANGPT2 protein was either absent or weakly expressed in Gc at all follicular stages. In Tc, minimal expression of ANGPT2 protein was detected in the preantral follicle (PF), whereas it was stronger in the early antral follicle (EAF) and preovulatory follicle (POF). TEK staining was absent in Gc but was intense in Tc at every follicular stage. Staining for VEGFA was either absent or weakly present in Gc and Tc in PF and EAF, although in POF it was stronger in Gc and Tc. Staining for KDR was absent in Gc and very low in Tc from PF. Gc and Tc of EAF showed positive staining for KDR and in POF the staining was stronger. These results were confirmed by western immunoblot. A similar pattern of expression of these proteins was observed in cycling rats. In conclusion, we observed that the protein expression of ANGPT1, ANGPT2, VEGFA and their receptors increased during follicular development in rats.

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“…The impact of vascular endothelial growth factor (VEGF) as a central regulator of angiogenesis in the ovary was demonstrated in studies using the techniques of gene or protein injection (Hazzard et al 2002, Shimizu et al 2003, Xu et al 2005. VEGF induces signal transduction in the cells via VEGF receptors that belong to the tyrosine-kinase receptor family.…”

Section: Introductionmentioning

confidence: 99%

Hormonal regulation and differential expression of neuropilin (NRP)-1 and NRP-2 genes in bovine granulosa cells

Shimizu¹,

Jayawardana²,

Nishimoto³

et al. 2006

Reproduction

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Although much is known about the biology of vascular endothelial growth factor (VEGF) and its receptors, little is known about the role of the VEGF receptors neuropilin (NRP)-1 and NRP-2 in the process of bovine follicle development. The aim of the present study was to examine the hormonal regulation of NRP-1 and NRP-2 mRNAs by real-time PCR in follicles from the bovine ovary and in cultured granulosa cells. The NRP-1 gene was expressed in the granulosa and theca cells in the post-selection (POF) and pre-selection (PRF) follicles in the bovine ovary. In contrast, the NRP-2 gene was expressed only in the theca cells in the POF and the PRF. The level of NRP-1 mRNA was significantly increased by treatment of the cultured granulosa cells with 10 ng/ml estradiol (E2). In contrast, the addition of progesterone (P4) to the culture medium decreased the expression of the NRP-1 gene. The level of NRP-1 mRNA was increased by 10 ng/ml E2 with or without 1 ng/ml P4, but the level of NRP-1 mRNA was decreased if the P4 level was increased to 10 ng/ml, even when 1 ng/ml E2 was also added. Folliclestimulating hormone did not stimulate the expression of the NRP-1 gene. These results are the first data showing that NRP-1, but not NRP-2, is expressed in the granulosa cells of bovine follicles and that NRP-1 gene expression is regulated by sex steroids. Our findings suggest the involvement of NRP-1 in follicle development in the cow.

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Intraovarian actions of anti-angiogenic agents disrupt periovulatory events during the menstrual cycle in monkeys

Cited by 42 publications

References 44 publications

Intrabursal injection of vascular endothelial growth factor trap in eCG-treated prepubertal rats inhibits proliferation and increases apoptosis of follicular cells involving the PI3K/AKT signaling pathway

Intrabursal injection of vascular endothelial growth factor trap in eCG-treated prepubertal rats inhibits proliferation and increases apoptosis of follicular cells involving the PI3K/AKT signaling pathway

Spatiotemporal analysis of the protein expression of angiogenic factors and their related receptors during folliculogenesis in rats with and without hormonal treatment

Hormonal regulation and differential expression of neuropilin (NRP)-1 and NRP-2 genes in bovine granulosa cells

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