Cyclin G1 inhibits the proliferation of mouse endometrial stromal cell in decidualization
Keywords:cyclin G1, decidualization, stromal cell, proliferation, mouse
Uterine stromal cell decidualization is a dynamic physiological process in which cell proliferation, differentiation and apoptosis are orchestrated and occur in a temporal and cell-specific manner. This process is important for successful embryo implantation. Many cell-cycle regulators are involved in decidualization. The protein cyclin G1 is a unique regulator of the cell cycle with dual functions in cell proliferation. It was reported that cyclin G1 is expressed in mouse uterine stromal cells during the period of peri-implantation. To prove the function of cyclin G1 in mouse uterine stromal cells during this period, immunohistochemistry was used to stain mouse uterine tissues on days 4-8 of pregnancy. The results showed obvious spatial and temporal expression of cyclin G1 in uterine stromal cells, and that it is expressed in the cells of the primary decidual zone (PDZ) on day 5 and secondary decidual zone (SDZ) on days 6 and 7, when the stromal cells experienced active proliferation and differentiation was initiated. Applying the decidualization model of cultured primary stromal cells in vitro, we further revealed that the expression of cyclin G1 is associated with decidualization of stromal cells induced by medroxyprogesterone acetate (MPA) and estradiol-17β (E2). RNA interference was used for the knockdown of cyclin G1 in the induced decidual cells. Flow cytometry analysis indicated that the proportion of cells in the S stage was increased, and decreased in the G2/M phase. Our study indicates that cyclin G1, as a negative regulator of the cell cycle, plays an important role in the process of decidualization in mouse uterine stromal cells by inhibiting cell-cycle progression.
Received: January 24, 2016; Revised: February 18, 2016; Accepted: February 22, 2016; Published online: September 16, 2016
How to cite this article: Xu Q, Yuan DZ, Zhang S, Qu T, Zhang SM, Yu LL, Zhan JH, Yue LM. Cyclin G1 inhibits the proliferation of mouse endometrial stromal cell in decidualization. Arch Biol Sci. 2017;69(1):71-81.
Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. 2011;17(2):242-53.
Koot YE, Macklon NS. Embryo implantation: biology, evaluation, and enhancement. Curr Opin Obstet Gynecol. 2013;25(4):274-79.
Filant J, Spencer TE. Endometrial glands are essential for blastocyst implantation and decidualization in the mouse uterus. Biol Reprod. 2013;88(4):93.
Dey SK, Lim H, Das SK, Reese J, Paria BC, Daikoku T, Wang H. Molecular cues to implantation. Endocr Rev. 2004;25(3):341-73.
Wang H, Dey SK. Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet. 2006;7(3):185-99.
Schlafke S, Enders AC. Cellular basis of interaction between trophoblast and uterus at implantation. Biol Reprod. 1975;12(1):41-65.
Ramathal CY, Bagchi IC, Taylor RN, Bagchi MK. Endometrial decidualization: of mice and men. Semin Reprod Med. 2010;28(1):17-26.
Li F, Devi YS, Bao L, Mao J, Gibori G. Involvement of cyclin D3, CDKN1A (p21), and BIRC5 (Survivin) in interleukin 11 stimulation of decidualization in mice. Biol Reprod. 2008; 78(1):127-33.
Das SK, Lim H, Paria BC, Dey SK. Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy. J Mol Endocrinol. 1999;22(1):91-101.
Tan Y, Li M, Cox S, Davis MK, Tawfik O, Paria BC, Das SK. HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation. Dev Biol. 2004;265(1):181-95.
Das SK. Cell cycle regulatory control for uterine stromal cell decidualization in implantation. Reproduction. 2009;137(6):889-99.
Seo HR, Lee DH, Lee HJ, Baek M, Bae S, Soh JW, Lee SJ, Kim J, Lee YS. Cyclin G1 overcomes radiation-induced G2 arrest and increases cell death through transcriptional activation of cyclin B1. Cell Death Differ. 2006;13(9):1475-84.
Maeda M, Ampo K, Kiryu-Seo S, Konishi H, Ohba N, Kadono C, Kiyama H. The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by ischemic and traumatic insults. Exp Neurol. 2005;193(2):350-60.
Kwon SH, Park JC, Ramachandran S, Cha SD, Kwon KY, Park JK, Park JW, Bae I, Cho CH. Loss of cyclin g1 expression in human uterine leiomyoma cells induces apoptosis. Reprod Sci. 2008;15(4):400-10.
Yuan DZ, Ding XL, Yu HL, Cheng Z, Tang XR, He Yaping, Zhang JH, Blok LJ, Hanifi-Moghaddam P, Burger CW, Yue LM. Progesterone-induced cyclin G1 inhibits the proliferation of endometrial epithelial cell and its possible molecular mechanism. Horm Metab Res. 2014;46(11):761-7.
Yue L, Daikoku T, Hou X, Li M, Wang H, Nojima H, Dey SK, Das SK. Cyclin G1 and cyclin G2 are expressed in the periimplantation mouse uterus in a cell-specific and progesterone-dependent manner: evidence for aberrant regulation with Hoxa-10 deficiency. Endocrinol. 2005;146(5):2424-33.
Li Q, Kannan A, Wang W, Demayo FJ, Taylor RN, Bagchi MK, Bagchi IC. Bone morphogenetic protein 2 functions via a conserved signaling pathway involving Wnt4 to regulate uterine decidualization in the mouse and the human. J Biol Chem. 2007;282(43):31725-32.
Lei W, Feng XH, Deng WB, Ni H, Zhang ZR, Jia B, Yang XL, Wang TS, Liu JL, Su RW, Liang XH, Qi QR, Yang ZM. Progesterone and DNA damage encourage uterine cell proliferation and decidualization through up-regulating ribonucleotide reductase 2 Expression during Early Pregnancy in Mice. J Biol Chem. 2012;287(19): 15174-92.
Li F, Devi YS, Bao L, Mao J, Gibori G. Involvement of Cyclin D3, CDKN1A (p21), and BIRC5 (Survivin) in Interleukin 11 Stimulation of Decidualization in Mice. Biol Reprod. 2008;78(1):127-33.
Rahman MA, Li M, Li P, Wang H, Dey SK, Das SK. Hoxa-10 deficiency alters region-specific gene expression and perturbs differentiation of natural killer cells during decidualization. Dev Biol. 2006;290(1):105-17.
Liang XH, Zhao ZA, Deng WB, Tian Z, Lei W, Xu X, Zhang XH, Su RW, Yang ZM. Estrogen regulates amiloride-binding protein 1 through CCAAT/enhancer-binding protein-beta in mouse uterus during embryo implantation and decidualization. Endocrinol. 2010;151(10):5007-16.
Zhang L, Patterson AL, Zhang L, Teixeira JM, Pru JK. Endometrial stromal b-catenin is required for steroid-dependent mesenchymal– epithelial cross talk and decidualization. Reprod Biol Endocrinol. 2012;10(3):1-13.
Kazuya Kusama, Mikihiro Yoshie, Kazuhiro Tamura, Takiko Daikoku, Tsutomu Takarada, and Eiichi Tachikawa. Possible roles of the cAMP-mediators EPAC and RAP1 in decidualization of rat uterus. Reprod. 2014;147(6): 897-906.
Tan J，Raja S，Davis M K，Tawfik O, Dey SK, Das SK.Evidence for coordinated interaction of Cyclin D3 with p21 and CDK6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation．Mech Dev. 2002;111(12):99-113．
Tong W , Pollard JW. Progesterone inhibits estrogen-induced cyclin D1 and cdk4 nuclear translocation, cyclin E- and cyclin A-cdk2 kinase activation, and cell proliferation in uterine epithelial cells in mice. Mol Cell Biol. 1999;19:2251-64.
Horne MC, Goolsby GL, Donaldson KL, Tran D, Neubauer M, Wahl AF. Cyclin G1 and cyclin G2 comprise a new family of cyclins with contrasting tissue-specific and cell cycle-regulated expression. J Biol Chem. 1996;271(11):6050-61.
Jensen MR, Factor VM, Fantozzi A, Helin K, Huh CG, Thorgeirsson SS. Reduced hepatic tumor incidence in cyclin G1-deficient mice. Hepatol. 2003;37(4):862-70.