Embryo-endometrial expression of leukemia inhibitory factor in the golden hamster (Mesocricetus auratus): increased expression during proestrous and window of implantation stages

2008 ◽  
Vol 20 (3) ◽  
pp. 440 ◽  
Author(s):  
Rajnish P. Rao ◽  
Bernd Fischer ◽  
Polani B. Seshagiri

Leukemia inhibitory factor (LIF) is a pleiotropic IL-6 family cytokine and its maternal uterine expression is critical for mouse blastocyst implantation. In the golden hamster (Mesocricetus auratus), although the blastocyst hatching phenomenon is quite interesting and LIF is shown to regulate hatching, information is not available on the embryonic and uterine expression of LIF and hormonal regulation of LIF expression during the peri-implantation period. The present investigation is aimed at studying embryonic and uterine expression of LIF during preimplantation hamster development. We observed embryonic expression of LIF mRNA and protein in the 8-cell, morula and blastocyst stages. In cycling females, uterine LIF mRNA expression was maximal during the oestrogen-dominant phase of the oestrous cycle, i.e. proestrous stage. Interestingly, during pregnancy, both LIF mRNA and protein were highly upregulated on Days 3.5 and 4 (‘window of implantation’), implying a role for this cytokine in blastocyst hatching and implantation. Cell type-specific localisation of LIF mRNA and protein was observed predominantly in luminal epithelium and uterine glands with faint staining being detected in the stroma. The hamster uterus encoded a ~4.2 kb LIF transcript whose coding region, when cloned and sequenced, showed a high degree of identity to the murine cDNA counterpart. These data demonstrate that: (1) hamster preimplantation embryos show LIF mRNA and protein expression; (2) uterine expression of LIF mRNA and protein was dependent on elevated levels of circulating oestrogen, and (3) there is a possible functional association of LIF with the peri-implantation development in the golden hamster.

Endocrinology ◽  
2021 ◽  
Author(s):  
Yamato Fukui ◽  
Yasushi Hirota ◽  
Tomoko Saito-Fujita ◽  
Shizu Aikawa ◽  
Takehiro Hiraoka ◽  
...  

Abstract Recent studies have demonstrated that the formation of an implantation chamber composed of a uterine crypt, an implantation-competent blastocyst, and uterine glands is a critical step in blastocyst implantation in mice. Leukemia inhibitory factor (LIF) activates signal transducer and activator of transcription 3 (STAT3) precursors via uterine LIF receptors (LIFRs), allowing successful blastocyst implantation. Our recent study revealed that the role of epithelial STAT3 is different from that of stromal STAT3. However, both are essential for blastocyst attachment, suggesting the different roles of epithelial and stromal LIFR in blastocyst implantation. However, how epithelial and stromal LIFR regulate the blastocyst implantation process remains unclear. To investigate the roles of LIFR in the uterine epithelium and stroma, we generated Lifr-floxed/lactoferrin (Ltf)-iCre (Lifr eKO) and Lifr-floxed/anti-Mullerian hormone receptor type 2 (Amhr2)-Cre (Lifr sKO) mice with deleted epithelial and stromal LIFR, respectively. Surprisingly, fertility and blastocyst implantation in the Lifr sKO mice were normal despite stromal STAT3 inactivation. In contrast, blastocyst attachment failed, and no implantation chambers were formed in the Lifr eKO mice with epithelial inactivation of STAT3. In addition, normal responsiveness to ovarian hormones was observed in the peri-implantation uteri of the Lifr eKO mice. These results indicate that the epithelial LIFR-STAT3 pathway initiates the formation of implantation chambers, leading to complete blastocyst attachment, and that stromal STAT3 regulates blastocyst attachment without stromal LIFR control. Thus, uterine epithelial LIFR is critical to implantation chamber formation and blastocyst attachment.


2013 ◽  
Vol 100 (4) ◽  
pp. 1160-1169.e2 ◽  
Author(s):  
Sujata Lalitkumar ◽  
Nageswara R. Boggavarapu ◽  
Judith Menezes ◽  
Evdokia Dimitriadis ◽  
Jian-Guo Zhang ◽  
...  

Contraception ◽  
2006 ◽  
Vol 74 (5) ◽  
pp. 419-425 ◽  
Author(s):  
Jayasree Sengupta ◽  
Parameswaran G.L. Lalitkumar ◽  
Abdur R. Najwa ◽  
Debabrata Ghosh

Reproduction ◽  
2006 ◽  
Vol 131 (2) ◽  
pp. 341-349 ◽  
Author(s):  
Haengseok Song ◽  
Hyunjung Lim

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.


1999 ◽  
Vol 72 (4) ◽  
pp. 713-719 ◽  
Author(s):  
Hsin-Fu Chen ◽  
Jin-Yuh Shew ◽  
Hong-Nerng Ho ◽  
Wei-Li Hsu ◽  
Yu-Shih Yang

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Zhou ◽  
Chenggang Li ◽  
Xiangshu Liu ◽  
Tao Zhang

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.


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