Document Detail


Expression of nitric oxide synthase and effect of substrate manipulation of the nitric oxide pathway in mouse ovarian follicles.
MedLine Citation:
PMID:  14688153     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Nitric oxide (NO) is a cell messenger with multiple actions in different biological systems, implicated in the control of follicle and oocyte function. NO is formed from L-arginine by isoforms of nitric oxide synthase (NOS) via NG-hydroxy-L-arginine, with L-citrulline as a byproduct. This study aimed to show how modulation of NO by manipulating NOS substrates would affect mouse follicle growth and ovulation in vitro, where vascular effects of NO are attenuated. METHODS: Immunohistochemistry [endothelial (eNOS) and inducible (iNOS)] and in situ hybridization (iNOS) were applied on mouse ovaries. Cultured follicles were also stained for iNOS by immunohistochemistry. For follicles cultured in the presence or absence of L-arginine, the ability of L-citrulline or NG-hydroxy-L-arginine to substitute for L-arginine was assessed in terms of follicle growth and ovulation. RESULTS: iNOS and eNOS were localized in oocytes and theca, with some staining in granulosa. iNOS mRNA occurred predominantly in granulosa and oocyte. Omission of L-arginine significantly reduced follicle survival and ovulation. Partial compensation for L-arginine withdrawal was achieved with L-citrulline and NG-hydroxy-L- arginine. Specific abnormalities of follicle growth were noted. CONCLUSIONS: NOS is present in mouse follicles, and its action is necessary at a local level for normal follicle development in vitro. Reduced growth, persistent basement membranes and reduced ovulation were associated with in vitro disruption of NO.
Authors:
Leila M Mitchell; C Richard Kennedy; Geraldine M Hartshorne
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Human reproduction (Oxford, England)     Volume:  19     ISSN:  0268-1161     ISO Abbreviation:  Hum. Reprod.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2003-12-22     Completed Date:  2004-08-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8701199     Medline TA:  Hum Reprod     Country:  England    
Other Details:
Languages:  eng     Pagination:  30-40     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / administration & dosage,  analogs & derivatives*,  pharmacology*
Citrulline / administration & dosage,  pharmacology*
Culture Media / chemistry
Dose-Response Relationship, Drug
Female
Mice
Mice, Inbred Strains
Nitric Oxide / metabolism*
Nitric Oxide Synthase / genetics,  metabolism*
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Ovarian Follicle / drug effects,  metabolism*
Ovulation / drug effects
RNA, Messenger / metabolism
Tissue Survival
Transferrin / pharmacology
Chemical
Reg. No./Substance:
0/Culture Media; 0/RNA, Messenger; 10102-43-9/Nitric Oxide; 11096-37-0/Transferrin; 372-75-8/Citrulline; 53054-07-2/N(omega)-hydroxyarginine; 74-79-3/Arginine; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos2 protein, mouse; EC 1.14.13.39/Nos3 protein, mouse

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