Document Detail

Injection of antiangiogenic agents into the macaque preovulatory follicle: disruption of corpus luteum development and function.
MedLine Citation:
PMID:  12108520     Owner:  NLM     Status:  MEDLINE    
Ovulation and conversion of the follicle into the corpus luteum involve remarkable changes in vascular permeability and neovascularization of the luteinizing granulosa layer. To evaluate the importance of these vascular events in follicle rupture and luteal development, sequential experiments were designed in which vehicle or angiogenic inhibitors (TNP-470 or angiostatin) were injected directly into the preovulatory follicle of rhesus monkeys during spontaneous menstrual cycles. After control injections, 13 of 14 animals exhibited serum levels of progesterone (P) during the subsequent luteal phase that were comparable to untreated animals in our colony. Following low-dose (400 pg/mL) TNP-470, serum P levels increased normally until d 8 of the luteal phase, but then declined prematurely by d 9 (p < 0.05 compared to controls) and remained below controls until menses. Following high-dose (2 microg/mL) TNP-470, serum P levels were diminished in the early luteal phase (d 3-5; p < 0.05 compared to controls), but reached typical levels at mid luteal phase, only to decline prematurely by d 9 (p < 0.05) and remain low until menses. Control ovaries displayed indices of follicle rupture (protruding stigmata) and luteinization. TNP-470-treated ovaries exhibited signs of distension (torn surface epithelium/tunica albuginea) and luteinization; however, a well-formed stigmata was not observed. A "trapped" oocyte was not observed in serial sections of developing corpora lutea from control or TNP-470-treated animals. However, the early corpus luteum of TNP-470-injected ovaries contained pockets of excessive numbers of blood cells that were absent in controls. Angiostatin did not alter serum P levels or ovarian morphology compared to controls. These data suggest that acute exposure to the antiangiogenic agent TNP-470 impairs the development and functional capacity of the primate corpus luteum in a dose-dependent manner. The results are consistent with a critical role for angiogenesis in cyclic ovarian function in primates.
Timothy M Hazzard; Richard M Rohan; Theodore A Molskness; John W Fanton; Robert J D'Amato; Richard L Stouffer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endocrine     Volume:  17     ISSN:  1355-008X     ISO Abbreviation:  Endocrine     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-07-10     Completed Date:  2002-12-24     Revised Date:  2010-06-24    
Medline Journal Info:
Nlm Unique ID:  9434444     Medline TA:  Endocrine     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-206     Citation Subset:  IM    
Division of Reproductive Sciences, Oregon Regional Primate Research Center/Oregon Health & Science University, Beaverton, USA.
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MeSH Terms
Angiogenesis Inhibitors / pharmacology*,  toxicity
Cell Count
Corpus Luteum / cytology,  drug effects
Estradiol / blood
Follicular Phase / physiology*
Luteinizing Hormone / blood
Macaca mulatta
Ovarian Follicle / drug effects,  physiology*
Paraffin Embedding
Peptide Fragments / pharmacology
Plasminogen / pharmacology
Progesterone / blood
Sesquiterpenes / pharmacology
Grant Support
Reg. No./Substance:
0/Angiogenesis Inhibitors; 0/Cyclohexanes; 0/Peptide Fragments; 0/Sesquiterpenes; 129298-91-5/O-(chloroacetylcarbamoyl)fumagillol; 50-28-2/Estradiol; 57-83-0/Progesterone; 86090-08-6/Angiostatins; 9001-91-6/Plasminogen; 9002-67-9/Luteinizing Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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