Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase

Sabra L Klein, David Carnovale, Arthur Burnett, Edward E Wallach, Howard A Zacur, Julie K. Crone, Valina Dawson, Randy J. Nelson, Ted M Dawson

Research output: Contribution to journalArticle

Abstract

Background: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). Materials and Methods: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alterations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. Results: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. Conclusions: The reproductive deficits in nNOS-/females are most likely due to alterations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.

Original languageEnglish (US)
Pages (from-to)658-664
Number of pages7
JournalMolecular Medicine
Volume4
Issue number10
StatePublished - 1998

Fingerprint

Nitric Oxide Synthase Type I
Ovulation
Protein Isoforms
Oocytes
Oviducts
Nitric Oxide
Nitric Oxide Synthase
Gonadotropins
Gonadotropin-Releasing Hormone
Rupture
Pharmacology
Equine Gonadotropins
Female Infertility
Chorionic Gonadotropin
Luteinizing Hormone
Fertility
Ovary
Proteins
Staining and Labeling

ASJC Scopus subject areas

  • Genetics

Cite this

Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase. / Klein, Sabra L; Carnovale, David; Burnett, Arthur; Wallach, Edward E; Zacur, Howard A; Crone, Julie K.; Dawson, Valina; Nelson, Randy J.; Dawson, Ted M.

In: Molecular Medicine, Vol. 4, No. 10, 1998, p. 658-664.

Research output: Contribution to journalArticle

@article{489e783d89bf4d84856039eab7be5fab,
title = "Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase",
abstract = "Background: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). Materials and Methods: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alterations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. Results: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. Conclusions: The reproductive deficits in nNOS-/females are most likely due to alterations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.",
author = "Klein, {Sabra L} and David Carnovale and Arthur Burnett and Wallach, {Edward E} and Zacur, {Howard A} and Crone, {Julie K.} and Valina Dawson and Nelson, {Randy J.} and Dawson, {Ted M}",
year = "1998",
language = "English (US)",
volume = "4",
pages = "658--664",
journal = "Molecular Medicine",
issn = "1076-1551",
publisher = "Feinstein Institute for Medical Research",
number = "10",

}

TY - JOUR

T1 - Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase

AU - Klein, Sabra L

AU - Carnovale, David

AU - Burnett, Arthur

AU - Wallach, Edward E

AU - Zacur, Howard A

AU - Crone, Julie K.

AU - Dawson, Valina

AU - Nelson, Randy J.

AU - Dawson, Ted M

PY - 1998

Y1 - 1998

N2 - Background: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). Materials and Methods: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alterations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. Results: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. Conclusions: The reproductive deficits in nNOS-/females are most likely due to alterations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.

AB - Background: Nitric oxide (NO) plays an important role in numerous reproductive processes. To date, most studies have assessed the role of NO by using nonspecific pharmacological inhibitors of the precursor to NO, nitric oxide synthase (NOS). These pharmacological NOS inhibitors suppress all isoforms of NOS; thus, the precise contribution of each isoform to female reproductive physiology is unknown. The purpose of this study was to determine the specific role of neuronal NOS (nNOS) in the regulation of ovulation in female mice lacking the gene that encodes for nNOS (nNOS-/-). Materials and Methods: Ovulation was assessed in wild-type (WT) and nNOS-/- female mice by examining the number of ovarian rupture sites and number of oocytes recovered from the oviducts following mating or exposure to exogenous gonadotropins (i.e., 5 IU pregnant mares serum gonadotropin [PMSG] and 5 IU human chorionic gonadotropin [hCG]). Ovulatory efficiency was determined as the number of ovulated oocytes per number of ovarian rupture sites. To examine whether ovulatory deficits in nNOS-/- mice were due to alterations in central mechanisms, plasma luteinizing hormone (LH) concentrations were assessed in WT and nNOS-/- mice that were challenged with 25 ng of gonadotropin-releasing hormone (GnRH). To determine whether ovulatory deficits in nNOS-/- mice were due to local ovulation processes, nerves innervating the reproductive tract of WT and nNOS-/- females were examined for the presence of nNOS protein. Results: There were substantial fertility deficits in nNOS-/- female mice; the nNOS-/- mice had fewer oocytes in their oviducts following spontaneous and gonadotropin-stimulated ovulation. Pituitary responsiveness to exogenous GnRH challenge was intact in nNOS-/- mice. Dense nNOS protein staining was observed in nerves innervating the reproductive tracts of WT mice. Conclusions: The reproductive deficits in nNOS-/females are most likely due to alterations in the transfer of oocytes from the ovaries to the oviducts during ovulation. These results suggest that defects in neuronally derived NO production may contribute to female infertility.

UR - http://www.scopus.com/inward/record.url?scp=0031761167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031761167&partnerID=8YFLogxK

M3 - Article

C2 - 9848082

AN - SCOPUS:0031761167

VL - 4

SP - 658

EP - 664

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

IS - 10

ER -