Expression of KRAS in the endometrium of early pregnant mice and its effect during embryo implantation

被引:15
作者
Long, Xia [1 ]
Zhang, Min [1 ]
Chen, Xuemei [1 ]
He, Junlin [1 ]
Ding, Yubin [1 ]
Zhang, Cuizhen [1 ]
Liu, Xueqing [1 ]
Wang, Yingxiong [1 ]
机构
[1] Chongqing Med Univ, Sch Publ Hlth, Reprod Biol Lab, Chongqing, Peoples R China
基金
中国国家自然科学基金;
关键词
endometrium; implantation; KRAS; pregnancy; EPIDERMAL-GROWTH-FACTOR; MOUSE UTERUS; EPITHELIAL-CELLS; UTERINE GLANDS; RAT UTERUS; DECIDUALIZATION; GENE; PROTEIN; WINDOW; TRANSFORMATION;
D O I
10.1016/j.rbmo.2015.04.005
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
This study investigated the expression pattern of Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in the endometrium of early-stage pregnant mice and its function during embryo implantation. The expression of KRAS was measured at the mRNA level using real-time polymerase chain reaction (PCR) and at the protein level using immunohistochemistry and western blotting. The expressions of KRAS mRNA and protein were not significantly different in the endometrium of pseudopregnant and early-stage pregnant mice. However, the immunohistochemistry results showed that KRAS was highly expressed in the decidualizing stromal cells on days 5-7 of mouse pregnancy and was enhanced in the epithelial cells as pregnancy progressed. The expression of KRAS protein was higher after the stromal cell was artificially decidualized in vivo and in vitro. Stromal cell proliferation was attenuated after down-regulating KRAS expression. After silencing KRAS in the mouse uterus, the embryo implantation rate was significantly reduced (P < 0.005). We speculate that KRAS may regulate the stromal cell proliferation and differentiation progress and then affect the embryo implantation process. This study reveals that KRAS plays an important role in regulating the embryo implantation process. (C) 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:51 / 61
页数:11
相关论文
共 36 条
[1]   Oncogenic K-ras drives cell cycle progression and phenotypic conversion of primary pancreatic duct epithelial cells [J].
Agbunag, C ;
Bar-Sagi, D .
CANCER RESEARCH, 2004, 64 (16) :5659-5663
[2]   Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation [J].
Bagot, CN ;
Troy, PJ ;
Taylor, HS .
GENE THERAPY, 2000, 7 (16) :1378-1384
[3]   DIFFERENTIALLY REGULATED IMMEDIATE-EARLY GENES IN THE RAT UTERUS [J].
BIGSBY, RM ;
LI, AX .
ENDOCRINOLOGY, 1994, 134 (04) :1820-1826
[4]  
CADUFF RF, 1995, AM J PATHOL, V146, P182
[5]   K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling [J].
Campbell, Paul M. ;
Groehler, Angela L. ;
Lee, Kwang M. ;
Ouellette, Michel M. ;
Khazak, Vladimir ;
Der, Channing J. .
CANCER RESEARCH, 2007, 67 (05) :2098-2106
[6]   Embryo implantation [J].
Carson, DD ;
Bagchi, I ;
Dey, SK ;
Enders, AC ;
Fazleabas, AT ;
Lessey, BA ;
Yoshinaga, K .
DEVELOPMENTAL BIOLOGY, 2000, 223 (02) :217-237
[7]   Mechanisms of implantation: strategies for successful pregnancy [J].
Cha, Jeeyeon ;
Sun, Xiaofei ;
Dey, Sudhansu K. .
NATURE MEDICINE, 2012, 18 (12) :1754-1767
[8]   Uterine glands: development, function and experimental model systems [J].
Cooke, Paul S. ;
Spencer, Thomas E. ;
Bartol, Frank F. ;
Hayashi, Kanako .
MOLECULAR HUMAN REPRODUCTION, 2013, 19 (09) :547-558
[9]   Expression of betacellulin and epiregulin genes in the mouse uterus temporally by the blastocyst solely at the site of its apposition is coincident with the ''window'' of implantation [J].
Das, SK ;
Das, N ;
Wang, J ;
Lim, H ;
Schryver, B ;
Plowman, GD ;
Dey, SK .
DEVELOPMENTAL BIOLOGY, 1997, 190 (02) :178-190
[10]   Cyclin D3 in the mouse uterus is associated with the decidualization process during early pregnancy [J].
Das, SK ;
Lim, H ;
Paria, BC ;
Dey, SK .
JOURNAL OF MOLECULAR ENDOCRINOLOGY, 1999, 22 (01) :91-101