Identification of phosphodiesterase 9A as a cyclic guanosine monophosphate-specific phosphodiesterase in germinal vesicle oocytes: A proposed role in the resumption of meiosis

Carol Hanna, Shan Yao, Xuemei Wu, Jeffrey Jensen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective: To identify a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) in nonhuman primate germinal vesicle (GV) oocytes and establish a proposed effect on oocyte maturation through preliminary experiments in mouse GV oocytes. Design: Controlled nonhuman primate and rodent experiments. Setting: Academic research institution. Animal(s): Rhesus macaques and B6/129F1 mice. Intervention(s): Stimulation of Rhesus macaques with follicle-stimulating hormone (FSH) to collect GV oocytes and cumulus for gene expression analysis, and stimulation of female mice with pregnant mare serum gonadotropin to collect GV oocytes. Main Outcome Measure(s): Expression of PDE transcript in primate GV oocytes and cumulus cells, measurement of fluorescence polarization of phosphodiesterase 3A (PDE3A) activity, and analysis of spontaneous resumption of meiosis in mouse GV oocytes. Result(s): Of five PDE transcripts detected in Rhesus GV oocytes, only PDE9A was cGMP-specific. The fluorescence polarization assays indicated cGMP has an inhibitory effect on PDE3A while the phosphodiesterase 9A (PDE9) inhibitor, BAY73-6691, does not. Similarly, BAY73-6691 had little effect on preventing spontaneous maturation in oocytes, but did augment the inhibitory effects of cGMP. Inclusion of 0 μM (control), 10 μM, 100 μM, and 1 mM BAY73-6691 statistically significantly increased the proportion of mouse oocytes maintaining GV arrest in the presence of the cGMP analog 8-Br-cGMP at 100 μM (8.8%, 11.4%, 18.8%, and 28%), 500 μM (21.1%, 38.1%, 74.5%, and 66.5%), and 1 mM (57.8%, 74.5%, 93.9%, and 94.0%), respectively. Conclusion(s): Phosphodiesterase 9A (PDE9A) is a cGMP-specific hydrolyzing enzyme present in primate oocytes, and PDE9 antagonists augment the inhibitory effect of cGMP during spontaneous in vitro maturation of GV mouse oocytes.

Original languageEnglish (US)
JournalFertility and Sterility
Volume98
Issue number2
DOIs
StatePublished - Aug 2012

Fingerprint

Cyclic GMP
Phosphoric Diester Hydrolases
Meiosis
Oocytes
Primates
Type 3 Cyclic Nucleotide Phosphodiesterases
Fluorescence Polarization
Phosphodiesterase Inhibitors
Macaca mulatta
Equine Gonadotropins
Cumulus Cells
Follicle Stimulating Hormone
Rodentia
Outcome Assessment (Health Care)

Keywords

  • cGMP
  • meiosis
  • oocyte
  • phosphodiesterase 3A
  • phosphodiesterase 9A

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

@article{0b895a46438a432bb8e2a420614eec0b,
title = "Identification of phosphodiesterase 9A as a cyclic guanosine monophosphate-specific phosphodiesterase in germinal vesicle oocytes: A proposed role in the resumption of meiosis",
abstract = "Objective: To identify a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) in nonhuman primate germinal vesicle (GV) oocytes and establish a proposed effect on oocyte maturation through preliminary experiments in mouse GV oocytes. Design: Controlled nonhuman primate and rodent experiments. Setting: Academic research institution. Animal(s): Rhesus macaques and B6/129F1 mice. Intervention(s): Stimulation of Rhesus macaques with follicle-stimulating hormone (FSH) to collect GV oocytes and cumulus for gene expression analysis, and stimulation of female mice with pregnant mare serum gonadotropin to collect GV oocytes. Main Outcome Measure(s): Expression of PDE transcript in primate GV oocytes and cumulus cells, measurement of fluorescence polarization of phosphodiesterase 3A (PDE3A) activity, and analysis of spontaneous resumption of meiosis in mouse GV oocytes. Result(s): Of five PDE transcripts detected in Rhesus GV oocytes, only PDE9A was cGMP-specific. The fluorescence polarization assays indicated cGMP has an inhibitory effect on PDE3A while the phosphodiesterase 9A (PDE9) inhibitor, BAY73-6691, does not. Similarly, BAY73-6691 had little effect on preventing spontaneous maturation in oocytes, but did augment the inhibitory effects of cGMP. Inclusion of 0 μM (control), 10 μM, 100 μM, and 1 mM BAY73-6691 statistically significantly increased the proportion of mouse oocytes maintaining GV arrest in the presence of the cGMP analog 8-Br-cGMP at 100 μM (8.8{\%}, 11.4{\%}, 18.8{\%}, and 28{\%}), 500 μM (21.1{\%}, 38.1{\%}, 74.5{\%}, and 66.5{\%}), and 1 mM (57.8{\%}, 74.5{\%}, 93.9{\%}, and 94.0{\%}), respectively. Conclusion(s): Phosphodiesterase 9A (PDE9A) is a cGMP-specific hydrolyzing enzyme present in primate oocytes, and PDE9 antagonists augment the inhibitory effect of cGMP during spontaneous in vitro maturation of GV mouse oocytes.",
keywords = "cGMP, meiosis, oocyte, phosphodiesterase 3A, phosphodiesterase 9A",
author = "Carol Hanna and Shan Yao and Xuemei Wu and Jeffrey Jensen",
year = "2012",
month = "8",
doi = "10.1016/j.fertnstert.2012.05.015",
language = "English (US)",
volume = "98",
journal = "Fertility and Sterility",
issn = "0015-0282",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Identification of phosphodiesterase 9A as a cyclic guanosine monophosphate-specific phosphodiesterase in germinal vesicle oocytes

T2 - A proposed role in the resumption of meiosis

AU - Hanna, Carol

AU - Yao, Shan

AU - Wu, Xuemei

AU - Jensen, Jeffrey

PY - 2012/8

Y1 - 2012/8

N2 - Objective: To identify a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) in nonhuman primate germinal vesicle (GV) oocytes and establish a proposed effect on oocyte maturation through preliminary experiments in mouse GV oocytes. Design: Controlled nonhuman primate and rodent experiments. Setting: Academic research institution. Animal(s): Rhesus macaques and B6/129F1 mice. Intervention(s): Stimulation of Rhesus macaques with follicle-stimulating hormone (FSH) to collect GV oocytes and cumulus for gene expression analysis, and stimulation of female mice with pregnant mare serum gonadotropin to collect GV oocytes. Main Outcome Measure(s): Expression of PDE transcript in primate GV oocytes and cumulus cells, measurement of fluorescence polarization of phosphodiesterase 3A (PDE3A) activity, and analysis of spontaneous resumption of meiosis in mouse GV oocytes. Result(s): Of five PDE transcripts detected in Rhesus GV oocytes, only PDE9A was cGMP-specific. The fluorescence polarization assays indicated cGMP has an inhibitory effect on PDE3A while the phosphodiesterase 9A (PDE9) inhibitor, BAY73-6691, does not. Similarly, BAY73-6691 had little effect on preventing spontaneous maturation in oocytes, but did augment the inhibitory effects of cGMP. Inclusion of 0 μM (control), 10 μM, 100 μM, and 1 mM BAY73-6691 statistically significantly increased the proportion of mouse oocytes maintaining GV arrest in the presence of the cGMP analog 8-Br-cGMP at 100 μM (8.8%, 11.4%, 18.8%, and 28%), 500 μM (21.1%, 38.1%, 74.5%, and 66.5%), and 1 mM (57.8%, 74.5%, 93.9%, and 94.0%), respectively. Conclusion(s): Phosphodiesterase 9A (PDE9A) is a cGMP-specific hydrolyzing enzyme present in primate oocytes, and PDE9 antagonists augment the inhibitory effect of cGMP during spontaneous in vitro maturation of GV mouse oocytes.

AB - Objective: To identify a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE) in nonhuman primate germinal vesicle (GV) oocytes and establish a proposed effect on oocyte maturation through preliminary experiments in mouse GV oocytes. Design: Controlled nonhuman primate and rodent experiments. Setting: Academic research institution. Animal(s): Rhesus macaques and B6/129F1 mice. Intervention(s): Stimulation of Rhesus macaques with follicle-stimulating hormone (FSH) to collect GV oocytes and cumulus for gene expression analysis, and stimulation of female mice with pregnant mare serum gonadotropin to collect GV oocytes. Main Outcome Measure(s): Expression of PDE transcript in primate GV oocytes and cumulus cells, measurement of fluorescence polarization of phosphodiesterase 3A (PDE3A) activity, and analysis of spontaneous resumption of meiosis in mouse GV oocytes. Result(s): Of five PDE transcripts detected in Rhesus GV oocytes, only PDE9A was cGMP-specific. The fluorescence polarization assays indicated cGMP has an inhibitory effect on PDE3A while the phosphodiesterase 9A (PDE9) inhibitor, BAY73-6691, does not. Similarly, BAY73-6691 had little effect on preventing spontaneous maturation in oocytes, but did augment the inhibitory effects of cGMP. Inclusion of 0 μM (control), 10 μM, 100 μM, and 1 mM BAY73-6691 statistically significantly increased the proportion of mouse oocytes maintaining GV arrest in the presence of the cGMP analog 8-Br-cGMP at 100 μM (8.8%, 11.4%, 18.8%, and 28%), 500 μM (21.1%, 38.1%, 74.5%, and 66.5%), and 1 mM (57.8%, 74.5%, 93.9%, and 94.0%), respectively. Conclusion(s): Phosphodiesterase 9A (PDE9A) is a cGMP-specific hydrolyzing enzyme present in primate oocytes, and PDE9 antagonists augment the inhibitory effect of cGMP during spontaneous in vitro maturation of GV mouse oocytes.

KW - cGMP

KW - meiosis

KW - oocyte

KW - phosphodiesterase 3A

KW - phosphodiesterase 9A

UR - http://www.scopus.com/inward/record.url?scp=84864483759&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864483759&partnerID=8YFLogxK

U2 - 10.1016/j.fertnstert.2012.05.015

DO - 10.1016/j.fertnstert.2012.05.015

M3 - Article

C2 - 22704629

AN - SCOPUS:84864483759

VL - 98

JO - Fertility and Sterility

JF - Fertility and Sterility

SN - 0015-0282

IS - 2

ER -