Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development

Zimmermann, Ralf; Hartman, T. D.; Kavic, Suzanne; Pauli, Samuel A.; Bőhlen, Peter; Sauer, Mark V.; Kitajewski, Jan

doi:10.1172/jci18740

Cited by 55 publications

(68 citation statements)

References 35 publications

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“…31 Encouraged by the various studies, many workers had tried cabergoline in OHSS prevention, administering the drug immediately after pick up or from the day of hCG administration and thus avoiding a possible detrimental effect on follicular growth and oocyte maturation due to VEGF system block, and found that none of the high risk patients treated, developed OHSS and data on pregnancy rates were comparable and implantation rates significantly higher than those observed in untreated high-responder controls. 32, 33 Youssef MA et al in a latest systematic review and meta-analysis have highlighted the prophylactic action of cabergoline, in lowering the incidence of OHSS and reiterated its efficacy.…”

Section: Efficacy Of the Drugmentioning

confidence: 99%

“…The early stages of pregnancy are highly dependent on ovarian and uterine angiogenesis as it is well known that VEGF is a key factor in endometrial neovascularisation. 33,36,37 Thus, this fundamental step in mammalian embryo implantation through VEGF-mediated angiogenesis could be intercepted by targeting VEGF with monoclonal antibodies. 38,39 However Alvarez et al in their study have presented that endometrial angiogenesis was not greatly altered, by the dose of Cb2 employed since neither implantation nor the overall ART outcome was affected.…”

mentioning

confidence: 99%

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VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: Current status

Naredi

Talwar

Kharb

2014

Medical Journal Armed Forces India

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Section: Efficacy Of the Drugmentioning

confidence: 99%

mentioning

confidence: 99%

VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: Current status

Naredi

Talwar

Kharb

2014

Medical Journal Armed Forces India

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“…Recent studies have shown that it exerts a crucial role during the transition from preovulatory follicles to ovulation , Zimmermann et al 2003 but few data describe the production of VEGF during the passage from pre-to periovulatory follicles and what role it exerts. At the end of each ovarian cycle, in fact, dominant follicle(s), selected from a cohort of growing antral structures, undergo ovulation in response to the luteinizing hormone (LH) surge and, subsequently, ovulate and differentiate into corpus luteum (CL) (Greenwald & Terranova 1988).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies performed on rodents and primates have shown that CL formation is completely impaired by VEGF immunoneutralization obtained using soluble receptors or receptor-blocking antibodies , Zimmermann et al 2003.…”

Section: Introductionmentioning

confidence: 99%

Spatio-temporal analysis of vascular endothelial growth factor expression and blood vessel remodelling in pig ovarian follicles during the periovulatory period

Martelli¹,

Berardinelli²,

Russo³

et al. 2006

Journal of Molecular Endocrinology

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Vascular endothelial growth factor (VEGF) expression pattern and blood vessel remodelling were evaluated during the transition from the preovulatory follicle to the corpus luteum (CL). To this end, prepubertal gilts were treated with equine chorionic gonadotrophin (eCG) to collect preovulatory follicles (60 h after eCG) and with human chorionic gonadotrophin (hCG) to obtain periovulatory follicles 18 h and 36 h later. The VEGF mRNA content was analysed by in situ hybridization, while protein localization in follicular fluid (FF) and in granulosa and theca compartments was evaluated by ELISA, immunohistochemistry or western blot. Blood vessel architecture and vascular area (VA) were investigated using immunohistochemistry for von Willenbrand Factor, a specific endothelial marker. Vascular remodelling was finally tested using Ki-67 immunocytochemistry as a proliferation marker, or -smooth muscle actin ( -SMA) as a specific mural cell marker. eCG-treated follicles showed high VEGF levels and two concentric blood vessel networks composed of proliferating endothelial cells without any association with mural components. hCG injection inhibited VEGF synthesis in the granulosa compartment and, as a consequence, the protein fell within the FF. In parallel, endothelial cell proliferation stopped and the VA decreased. Close to ovulation, VEGF production restarted in both follicular compartments and VEGF mRNA content significantly increased in the theca layer. Changes in follicular VEGF secretion were observed; the protein disappeared from FF and was observed in the extracellular matrix. An active angiogenesis characterized the follicle; endothelial cell proliferation was associated with a recruitment of -SMA-positive mural cells. The data presented in this work showed that, in the phases preceding ovulation, a complete vascular remodelling occurs, characterized by both an evident neovascularization and the appearance of blood vessels presenting smooth musculature which could be involved in CL formation after ovulation.

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“…A study on mice demonstrated that administering a KDR antibody acts as an inhibitor of gonadotropin-dependent follicular angiogenesis, which in turn impedes development of mature antral follicles (33). It was also observed that inhibition of VEGFA with a VEGFA trap antagonist caused a reduction in follicular angiogenesis and development, as well as a reduction in VEGFR1 (also referred to as FLT1) and KDR expression in monkeys (34). Therefore, ovulation and the subsequent development and functional capacity of the corpus luteum may be inhibited by intrafollicular injection of a VEGFA antagonist (35).…”

Section: Vegf and Follicular Growthmentioning

confidence: 99%

Ovarian function following targeted anti-angiogenic therapy with bevacizumab

Imai

Ichigo

Matsunami

et al. 2017

Molecular and Clinical Oncology

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Abstract. Improvements in cancer therapy have enabled further insight into the long-term effects of treatment, including the highly prevalent gonadal failure. The focus of treatment has been shifted to the preservation of fertility, which may be achieved by preventing ovarian toxicity. To this end, new molecular-targeted agents, including monoclonal antibodies, have been developed and used in a standard procedure for managing different cancers. However, the prolonged antitumor activity of these drugs may cause the emergence of new toxic effects. The aim of the present review was to discuss the leading toxic effect of the anti-angiogenic agent bevacizumab on ovarian function in female patients of reproductive age, which may be observed and expected during in clinical practice. The majority of bevacizumab-induced side effects are expected to be transient and eliminated within the anticipated drug clearance time frame; however, fundamental investigations on these effects are required for generating more evidence-based practice guidelines.

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Vascular endothelial growth factor receptor 2–mediated angiogenesis is essential for gonadotropin-dependent follicle development

Cited by 55 publications

References 35 publications

VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: Current status

VEGF antagonist for the prevention of ovarian hyperstimulation syndrome: Current status

Spatio-temporal analysis of vascular endothelial growth factor expression and blood vessel remodelling in pig ovarian follicles during the periovulatory period

Ovarian function following targeted anti-angiogenic therapy with bevacizumab

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