Angiogenesis gene expression in mouse uterus during the common pathway of parturition.
OBJECTIVE
The objective of the study was to investigate changes in the expression of angiogenesis-related genes during the common terminal pathway of parturition including spontaneous labor at term, as well as preterm labor (PTL), induced by either bacteria or ovariectomy.


METHODS
Preterm pregnant mice (14.5 days of gestation) were treated with the following: (1) intrauterine injection of media; (2) intrauterine injection of heat-inactivated Escherichia coli; (3) ovariectomy; and (4) sham operation. Tissues from mice at term (19.5 days of gestation) were collected at term not in labor, term in labor, and 12 hours postpartum. Angiogenesis-related gene expression levels were quantitated by the measurement of specific mRNAs in uterine tissue by RT-qPCR and analyzed by repeated-measures analysis of variance.


RESULTS
The following results were found: (1) microarray analysis of the uterine transcriptome indicated an enrichment for the gene ontology category of angiogenesis in bacteria-induced PTL samples (P < or = .093); (2) several genes related to angiogenesis demonstrated significantly increased expression in samples in either term spontaneous labor or preterm labor; and (3) qRT-PCR measurements demonstrated that spontaneous term labor and preterm labor induced by either bacteria or ovariectomy all substantially increased the expression of multiple angiogenesis-related genes (P < or = .0003; Angpt2, Ctgf, Cyr61, Dscr1, Pgf, Serpine1, Thbs1, and Wisp 1).


CONCLUSIONS
Spontaneous labor at term, as well as pathologically induced preterm labor, all result in greatly increased expression of angiogenesis-related genes in the uterus.
Haddad
Ramsi
R
Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Romero
Roberto
R
Gould
Barbara R
BR
Tromp
Gerard
G
Gotsch
Francesca
F
Edwin
Samuel S
SS
Zingg
Hans H
HH
D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D055511:CCN Intercellular Signaling Proteins; D055513:Connective Tissue Growth Factor; D055515:Cysteine-Rich Protein 61; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D017874:Immediate-Early Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D051379:Mice; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D007752:Obstetric Labor, Premature / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000502:physiology; D010052:Ovariectomy; D036801:Parturition / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D049590:Postpartum Period / Q000502:physiology; D011247:Pregnancy; D011518:Proto-Oncogene Proteins; D019700:Thrombospondin 1 / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D014599:Uterus / Q000378:metabolism*
D000091302:Angiopoietin-Like Protein 2; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C485793:Angptl2 protein, mouse; D055511:CCN Intercellular Signaling Proteins; C491850:CCN1 protein, mouse; C526318:CCN2 protein, mouse; C492067:CCN4 protein, mouse; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D019700:Thrombospondin 1; D055513:Connective Tissue Growth Factor