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.

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 Effect of Irisin on LIF and integrin αvβ3 in rats of implantation failure

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Zhou ◽  
Chenggang Li ◽  
Xiangshu Liu ◽  
Tao Zhang
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Integrin Αvβ3 ◽  
Treated Group ◽  
Inhibitory Factor ◽  
Implantation Failure ◽  
Failure Model ◽  
Pregnant Rats ◽  
The Poor ◽  
Group I ◽  
Blastocyst Implantation

Abstract Objective The aim of this study is to investigate the effect of irisin on leukemia inhibitory factor (LIF) and integrin αvβ3 in implantation failure uterus. Methods Early pregnant rats were randomly divided into normal group (N), mifepristone treated group (M), irisin group (I) and progestin group (P). The implantation failure model was established using mifepristone. Second, we evaluated the average number of embryos and detected the expression of LIF and integrin αvβ3 protein and mRNA in endometrium. Results Compared with group M, the average number of embryos was significantly higher in group N, P and I, the expression of LIF and integrin αvβ3 in endometrium was significantly higher in group N, P and I. Conclusion Irisin could improve the poor receptive state of endometrium by promoting LIF and integrin αvβ3 secretion to improve blastocyst implantation in rats of implantation failure.

scholarly journals HB-EGF regulates Prss56 expression during mouse decidualization via EGFR/ERK/EGR2 signaling pathway

2017 ◽  
Vol 234 (3) ◽  
pp. 247-254 ◽  
Author(s):  
Jie Liu ◽  
Fei Gao ◽  
Yue-Fang Liu ◽  
Hai-Ting Dou ◽  
Jia-Qi Yan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Implantation Site ◽  
Mouse Uterus ◽  
Delayed Implantation ◽  
Initial Stage ◽  
And Function ◽  
Key Steps

Embryo implantation and decidualization are key steps for successful reproduction. Although numerous factors have been identified to be involved in embryo implantation and decidualization, the mechanisms underlying these processes are still unclear. Based on our preliminary data, Prss56, a trypsin-like serine protease, is strongly expressed at implantation site in mouse uterus. However, the expression, regulation and function of Prss56 during early pregnancy are still unknown. In mouse uterus, Prss56 is strongly expressed in the subluminal stromal cells at implantation site on day 5 of pregnancy compared to inter-implantation site. Under delayed implantation, Prss56 expression is undetected. After delayed implantation is activated by estrogen, Prss56 is obviously induced at implantation site. Under artificial decidualization, Prss56 signal is seen at the primary decidual zone at the initial stage of artificial decidualization. When stromal cells are induced for in vitro decidualization, Prss56 expression is significantly elevated. Dtprp expression under in vitro decidualization is suppressed by Prss56 siRNA. In cultured stromal cells, HB-EGF markedly stimulates Prss56 expression through EGFR/ERK pathway. Based on promoter analysis, we also showed that Egr2 is involved in Prss56 regulation by HB-EGF. Collectively, Prss56 expression at implantation site is modulated by HB-EGF/EGFR/ERK signaling pathway and involved in mouse decidualization.

Polyethylene glycated leukemia inhibitory factor antagonist inhibits human blastocyst implantation and triggers apoptosis by down-regulating embryonic AKT

2013 ◽  
Vol 100 (4) ◽  
pp. 1160-1169.e2 ◽  
Author(s):  
Sujata Lalitkumar ◽  
Nageswara R. Boggavarapu ◽  
Judith Menezes ◽  
Evdokia Dimitriadis ◽  
Jian-Guo Zhang ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Human Blastocyst ◽  
Blastocyst Implantation ◽  
Factor Antagonist

Monoclonal anti-leukemia inhibitory factor antibody inhibits blastocyst implantation in the rhesus monkey

Contraception ◽  
2006 ◽  
Vol 74 (5) ◽  
pp. 419-425 ◽  
Author(s):  
Jayasree Sengupta ◽  
Parameswaran G.L. Lalitkumar ◽  
Abdur R. Najwa ◽  
Debabrata Ghosh
Keyword(s):  
Rhesus Monkey ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Factor ◽  
Blastocyst Implantation

scholarly journals Conversion of ES cells to columnar epithelia by hensin and to squamous epithelia by laminin

2004 ◽  
Vol 166 (7) ◽  
pp. 1093-1102 ◽  
Author(s):  
Jiro Takito ◽  
Qais Al-Awqati
Keyword(s):  
Es Cells ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Cell Types ◽  
Collagen Type Iv ◽  
Visceral Endoderm ◽  
Type Iv ◽  
Squamous Epithelia ◽  
Blastocyst Implantation ◽  
Columnar Cells

Single-layered epithelia are the first differentiated cell types to develop in the embryo, with columnar and squamous types appearing immediately after blastocyst implantation. Here, we show that mouse embryonic stem cells seeded on hensin or laminin, but not fibronectin or collagen type IV, formed hemispheric epithelial structures whose outermost layer terminally differentiated to an epithelium that resembled the visceral endoderm. Hensin induced columnar epithelia, whereas laminin formed squamous epithelia. At the egg cylinder stage, the distal visceral endoderm is columnar, and these cells begin to migrate anteriorly to create the anterior visceral endoderm, which assumes a squamous shape. Hensin expression coincided with the dynamic appearance and disappearance of columnar cells at the egg cylinder stage of the embryo. These expression patterns, and the fact that hensin null embryos (and those already reported for laminin) die at the onset of egg cylinder formation, support the view that hensin and laminin are required for terminal differentiation of columnar and squamous epithelial phenotypes during early embryogenesis.

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