Maternal Smad3 deficiency compromises decidualization in mice.
Transforming growth factor (TGF)-β and activin, members of TGF-β superfamily, are abundantly expressed in the endometrium and regulate decidualization of endometrial stroma. Smad2 and Smad3 are receptor-regulated Smads (R-Smads) that transduce extracellular TGF-β/activin/Nodal signaling. In situ hybridization results showed that Smad3 was highly expressed in the decidual zone during the peri-implantation period in mice. By using artificial decidualization, we found that Smad3 null mice showed partially compromised decidualization. We therefore hypothesized that Smad2 might compensate for the function of Smad3 during the process of decidualization. Smad2 was also highly expressed in the decidual zone and phosphorylated Smad2 was much more abundantly increased in the deciduoma of Smad3 null mice than for wild-type (WT) mice. We further employed an in vitro uterine stromal cell decidualization model, and found that decidual prolactin-related protein (dPRP) and cyclin D3, which are well-known markers for decidual cells, were significantly down-regulated in Smad3 null decidual cells, and were much more significantly reduced when the expression of Smad2 was simultaneously silenced by its siRNA (P < 0.05). However, the expression levels of dPRP and cyclin D3 remained the same when Smad2 was silenced in WT decidual cells. Collectively, these findings provide evidence for an important role of Smad3 in decidualization and suggest that Smad2 and Smad3 may have redundant roles in decidualization.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Kun-Qing
KQ
Zhao
Hai-Yan
HY
Lin
Cheng
C
Zhu
Xiao
X
Yang
Hongmei
H
Wang
D000818:Animals; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D010766:Phosphorylation; D011247:Pregnancy; D061251:Primary Cell Culture / Q000379:methods; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D034741:RNA, Small Interfering; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; D015232:Dinoprostone