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


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

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.