Expression of Smad2 and Smad4, transforming growth factor-beta signal transducers in rat endometrium during the estrous cycle, pre-, and peri-implantation.
SMADs are intracellular signaling molecules that transmit signals elicited by members of transforming growth factor-beta (TGF-beta) superfamily. To decipher the mechanism of TGF-beta signaling during the estrous cycle and implantation, we performed in situ hybridization to investigate the expression patterns of mRNAs for Smad2 and Smad4 in rat endometrium during the estrous cycle and on Days 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 of pregnancy. Intense epithelial expression of Smad2 mRNA at diestrus and proestrus was reduced at estrus and metaestrus, while Smad4 maintained its constitutive expression during the estrous cycle. During pre-implantation, both Smads were accumulated in the luminal epithelium and the glandular epithelium. Contrary to the dramatic Smad4 expression, Smad2 was highly down-regulated on Day 2.5 and was increased on Day 3.5. During peri-implantation, both Smads were expressed in the luminal epithelium, subepithelial stroma, and the primary decidual zone. Smad4 was down-modulated on Day 5.5. These results suggest that (a) both Smads are involved in the tissue remodeling of cycling and pregnant rat uteri; (b) TGF-beta signaling functions mainly in the epithelium during pre-implantation and Smad2 is involved in the endometrial switch from the neutral phase to the receptive phase; (c) TGF-beta signaling is down-regulated at the time when trophoblast invasion begins and both Smads are involved in the formation of the primary decidual zone.
Lin
Hai-Yan
HY
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 25 Bei Si Huan Xi Lu, Haidian District, Beijing 100080, China.
Wang
Hong-Mei
HM
Li
Qing-Lei
QL
Liu
Dong-Lin
DL
Zhang
Xuan
X
Liu
Guo-Yi
GY
Qian
Dong
D
Zhu
Cheng
C
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D010064:Embryo Implantation; D047108:Embryonic Development; D004717:Endometrium / Q000378:metabolism*; D030762:Estrous Cycle; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D017403:In Situ Hybridization; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051899:Smad2 Protein; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000502:physiology
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta