Dopamine receptor 2 activation inhibits ovarian vascular endothelial growth factor secretion in an ovarian hyperstimulation syndrome OHSS animal model Implications for treatment of OHSS with dopamine receptor 2 agonists

Dopamine receptor 2 agonist prevents vascular permeability in an ovarian hyperstimulation syndrome rat model by decreasing ovarian vascular endothelial growth factor production.

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Authors

Hortensia Ferrero, Ph.D., Carmen M. García-Pascual, Ph.D., María Gaytán, Ph.D., Concepción Morales, Ph.D., Carlos Simón, M.D., Francisco Gaytán, M.D., Antonio Pellicer, M.D., Raúl Gómez, Ph.D.

Volume 102, Issue 5, Pages 1468–1476.e1

Abstract

Objective:

To explore whether a dopamine receptor 2 agonist (D2-ag) can prevent ovarian hyperstimulation syndrome (OHSS) in a rat model by decreasing ovarian vascular endothelial growth factor (VEGF) production.

Design:

Experimental study in an OHSS animal model.

Setting:

University-affiliated infertility center.

Patient(s):

Immature Wistar rats.

Intervention(s):

Immature rats were stimulated with gonadotropins to mimic OHSS and treated with a D2-ag and/or D2-antagonists (D2-ant). Vascular permeability (VP) was measured at the endpoint, and ovaries were collected to assess the effects of these drugs on VEGF production.

Main Outcome Measure(s):

VP was estimated by measuring the peritoneal extravasation of a previously injected dye. Ovarian VEGF mRNA expression and VEGF protein levels were assessed by quantitative real-time PCR and Western blots, respectively.

Result(s):

The D2-ag exerted a reduction in VP that was associated with a drastic decrease in VEGF protein production in OHSS rat ovaries. The effects of this D2-ag on VP and VEGF protein levels were partially reversed by concomitant administration of a D2-ant. Ovarian VEGF mRNA expression levels were unaffected by these drugs in OHSS rats.

Conclusion(s):

D2-ags prevent increased VP in OHSS rats by decreasing ovarian VEGF production, very likely through a D2-mediated post-transcriptional mechanism. Given the dose-dependent inhibitory effect of D2-ags on ovarian VEGF production reported herein, we infer that current OHSS therapies used in humans may be improved by increasing the intraovarian concentration of D2-ags in these patients.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)01881-0/fulltext


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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