Granulated metrial gland cells in the murine uterus: localization, kinetics, and the functional role in angiogenesis during pregnancy.
Granulated metrial gland (GMG) cells are a major immune cell population in the murine pregnant uterus, and contribute to the maintenance of pregnancy by functioning as uterus-specific natural killer (NK) cells. In order to reveal their kinetics, activation, and functional roles in pregnancy, we conducted quantitative and immunohistochemical analyses in normal and immuno-modulator-treated mice. Under a light microscope, GMG cells were identified by red cytoplasmic granules in periodic-acid-Schiff (PAS)-stained sections. They progressively increased in number and size with the peak at day 12-14 of pregnancy in the decidua and metrial gland. New vessel formation was most prominent around day 8, and the total vascular area reached the peak at day 13. GMG cells were often located near the blood vessels, and expressed vascular endothelial growth factor (VEGF), suggesting their possible inducing role in angiogenesis during the development of decidua/metrial gland. While blood vessels in the non-pregnant uterus were negative for vascular cell adhesion molecule (VCAM)-1, those in the pregnant one were positive. Treatment with neutralizing antibody against VCAM-1, however, did not decrease the number of GMG cells. On the other hand, mitosis of GMG cells was frequently observed. These data suggest that the increment of GMG cells during pregnancy may largely result from local proliferation in the uterus rather than an increased influx of precursor cells. Although we attempted to induce in vivo activation of GMG cells by administration of interleukin-12 (IL-12) or alpha-galactosylceramide, a potent activator for natural killer-T (NK-T) cells, the number of GMG cells did not appreciably increase. The present study has demonstrated that GMG cells locally proliferate in the pregnant uterus, not being related to VCAM-1 expression by the uterine vasculature or systemic activation of NK cells and NK-T cells, and seem to be involved in angiogenesis in the pregnant uterus through VEGF production.
Wang
Chunlian
C
Department of Anatomy, Osaka City University Medical School, Osaka 545-8585, Japan.
Tanaka
Tetsuji
T
Nakamura
Hiroaki
H
Umesaki
Naohiko
N
Hirai
Kouzo
K
Ishiko
Osamu
O
Ogita
Sachio
S
Kaneda
Kenji
K
D000818:Animals; D003656:Decidua / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology; D008222:Lymphokines / Q000378:metabolism; D008791:Metrial Gland / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D014599:Uterus / Q000098:blood supply* / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors