scholarly journals Uterine Msx-1 and Wnt4 Signaling Becomes Aberrant in Mice with the Loss of Leukemia Inhibitory Factor or Hoxa-10: Evidence for a Novel Cytokine-Homeobox-Wnt Signaling in Implantation

2004 ◽  
Vol 18 (5) ◽  
pp. 1238-1250 ◽  
Author(s):  
Takiko Daikoku ◽  
Haengseok Song ◽  
Yong Guo ◽  
Anne Riesewijk ◽  
Sietse Mosselman ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Gene Targeting ◽  
Leukemia Inhibitory Factor ◽  
Homeobox Gene ◽  
Signaling Network ◽  
Mutant Mice ◽  
Inhibitory Factor ◽  
Mouse Uterus ◽  
Reciprocal Interaction

Abstract Successful implantation absolutely depends on the reciprocal interaction between the implantation-competent blastocyst and the receptive uterus. Expression and gene targeting studies have shown that leukemia inhibitory factor (LIF), a cytokine of the IL-6 family, and Hoxa-10, an abdominalB-like homeobox gene, are crucial to implantation and decidualization in mice. Using these mutant mice, we sought to determine the importance of Msx-1 (another homeobox gene formerly known as Hox-7.1) and of Wnt4 (a ligand of the Wnt family) signaling in implantation because of their reported functions during development. We observed that Msx-1, Wnt4, and a Wnt antagonist sFRP4 are differentially expressed in the mouse uterus during the periimplantation period, suggesting their role in implantation. In addition, we observed an aberrant uterine expression of Msx-1 and sFRP4 in Lif mutant mice, and of Wnt4 and sFRP4 in Hoxa-10 mutant mice, further reinforcing the importance of these signaling pathways in implantation. Collectively, the present results provide evidence for a novel cytokine-homeotic-Wnt signaling network in implantation.

scholarly journals Implantation Failure in Female Kiss1−/− Mice Is Independent of Their Hypogonadic State and Can Be Partially Rescued by Leukemia Inhibitory Factor

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 3065-3078 ◽  
Author(s):  
Michele Calder ◽  
Yee-Ming Chan ◽  
Renju Raj ◽  
Macarena Pampillo ◽  
Adrienne Elbert ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Hypogonadotropic Hypogonadism ◽  
Embryo Implantation ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Implantation Failure ◽  
Mouse Uterus ◽  
Female Mice ◽  
Wild Type Female ◽  
Neuroendocrine Axis

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1−/− female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1+/− embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse uterus, and we suggest that it is the absence of uterine kisspeptin signaling that underlies the implantation failure. This absence, however, does not prevent the closure of the uterine implantation chamber, proper alignment of the embryo, and the ability of the uterus to undergo decidualization. Instead, the loss of Kiss1 expression specifically disrupts embryo attachment to the uterus. We observed that on the day of implantation, leukemia inhibitory factor (Lif), a cytokine that is absolutely required for implantation in mice, is weakly expressed in Kiss1−/− uterine glands and that the administration of exogenous Lif to hormone-primed Kiss1−/− female mice is sufficient to partially rescue implantation. Taken together, our study reveals that uterine kisspeptin signaling regulates glandular Lif levels, thereby identifying a novel and critical role for kisspeptin in regulating embryo implantation in the mouse. This study provides compelling reasons to explore this role in other species, particularly livestock and humans.

scholarly journals Identification of Genes Regulated by Leukemia-Inhibitory Factor in the Mouse Uterus at the Time of Implantation

2004 ◽  
Vol 18 (9) ◽  
pp. 2185-2195 ◽  
Author(s):  
J. R. A. Sherwin ◽  
T. C. Freeman ◽  
R. J. Stephens ◽  
S. Kimber ◽  
A. G. Smith ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Mouse Uterus

Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy

1995 ◽  
Vol 42 (4) ◽  
pp. 407-414 ◽  
Author(s):  
Zeng-Ming Yang ◽  
Su-Ping Le ◽  
Dong-Bao Chen ◽  
Juan Cota ◽  
Valentina Siero ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Mouse Uterus

scholarly journals Requirement of Leukemia Inhibitory Factor or Epidermal Growth Factor for Pre-Implantation Embryogenesis via JAK/STAT3 Signaling Pathways

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153086 ◽  
Author(s):  
En-Hui Cheng ◽  
Jer-Yuh Liu ◽  
Tsung-Hsein Lee ◽  
Chun-Chia Huang ◽  
Chung-I Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Signaling Pathways ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Stat3 Signaling ◽  
Epidermal Growth

scholarly journals Evidence for heterodimeric association of leukemia inhibitory factor (LIF) receptor and gp130 in the mouse uterus for LIF signaling during blastocyst implantation

Reproduction ◽  
2006 ◽  
Vol 131 (2) ◽  
pp. 341-349 ◽  
Author(s):  
Haengseok Song ◽  
Hyunjung Lim
Keyword(s):  
Stromal Cells ◽  
Leukemia Inhibitory Factor ◽  
Expression Patterns ◽  
Cell Types ◽  
Inhibitory Factor ◽  
Second Phase ◽  
Implantation Failure ◽  
Mouse Uterus ◽  
Delayed Implantation ◽  
Blastocyst Implantation

Implantation failure in mice lacking leukemia inhibitory factor (LIF) establishes that this cytokine is crucial to this process. LIF transcripts are expressed in the uterus in a biphasic manner: LIF is expressed in the gland on the morning of day 4 and again in stromal cells surrounding the blastocyst with the onset of implantation in the evening of day 4 of pregnancy. However, it is not yet clear whether both phases of LIF expression are required for implantation, since the receptor usage by uterine LIF still remains elusive. Here we have provided evidence that major cell types expressing theLIF receptor (LIFR) and its signal transducing partner gp130 are mostly disparate in the mouse uterus during the glandular LIF expression in the morning of day 4. In contrast, LIFR and gp130 expressions overlap in the luminal epithelium at the time of blastocyst attachment on the evening of day 4 when the second phase of LIF expression occurs in stromal cells surrounding the blastocyst, suggesting that LIF participates in implantation in a paracrine manner. Similar expression patterns for LIFR and gp130 were observed when a delayed implantation model was used. For example, a transient overlapping expression of LIFR and gp130 was evident at 12 h after estrogen-induced termination of delayed implantation. Coimmunoprecipitation experiments showed that LIFR and gp130 form heterodimers and are available for LIF signaling at the time of blastocyst attachment. We have also shown that an intra-peritoneal administration of recombinant LIF in LIF-deficient pregnant mice on the evening of day 4, close to the time when the second phase of LIF expression is normally observed, is sufficient to rescue implantation failure, and that there is no evidence of antagonistic action by soluble forms of the receptors. Collectively, our results have provided evidence that LIFR and gp130 form a functional heterodimer in the uterus during the attachment reaction to direct LIF signaling.

Sign in / Sign up

Export Citation Format

Share Document