Impairment of decidualization in SRC-deficient mice.
Many signaling events induced by ovarian steroid hormones, cytokines, and growth factors are involved in the process of decidualization of human and rodent endometrium. We have reported previously that tyrosine kinase activation of SRC functionally participates in decidualization of human endometrial stromal cells. To address its essential role in decidualization, we examined, using wild-type and Src knockout mice, whether the process of decidualization was impaired in the absence of SRC. Immunohistochemistry using an antibody specific for the active form of SRC revealed that the active SRC was expressed prominently in the decidualizing stromal cells of the pregnant wild-type mouse. Moreover, the active SRC was upregulated in the uterine horn with artificially stimulated decidual reaction. In comparison with wild-type and Src heterozygous mice, the uterus of Src null mice showed no apparent decidual response following artificial stimulation. Ovarian steroid-induced decidualization in vitro, as determined by morphological changes and expression of decidual/trophoblast prolactin-related protein and prostaglandin-endoperoxide synthase 2 (also known as Cox2), both of which are decidualization markers, did not occur in a timely fashion in endometrial stromal cells isolated from the uteri of SRC-deficient mice compared to those from wild-type and Src heterozygous mice. Our results collectively suggest that SRC is an indispensable signaling component for maximal decidualization in mice.
Shimizu
Aki
A
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo 160-8582, Japan.
Maruyama
Tetsuo
T
Tamaki
Kayoko
K
Uchida
Hiroshi
H
Asada
Hironori
H
Yoshimura
Yasunori
Y
D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003656:Decidua / Q000187:drug effects / Q000503:physiopathology*; D033301:Deciduoma / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D011388:Prolactin / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D012715:Sesame Oil / Q000494:pharmacology; D015854:Up-Regulation; D014599:Uterus / Q000166:cytology / Q000201:enzymology; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
C489796:Dtprp protein, mouse; D011374:Progesterone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D012715:Sesame Oil; D011388:Prolactin; D051546:Cyclooxygenase 2; D019061:src-Family Kinases