Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor

Jrgang Cheng

Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor

Jrgang Cheng * §

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§ National Cancer Institute at Frederick

Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor

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Abstract

Uterine receptivity needs to be synchronized with embryonic development, so the blastocyst stage of the embryo can implant. Leukemia Inhibitory Factor (LIF) is an essential factor for implantation, which is involved in the initiation of the window of implantation. However, the process by which the LIF signal pathway is transduced in the uterine luminal epithelium (LE) that leads to uterine receptivity is not completely elucidated. We tested the ability of cellular signaling inhibitors to disrupt uterine support of the embryo. Only Tyrphostin-AG490, an inhibitor of Jak2, can interfere with LIF signaling. Not only can AG490 reduce phosphorylated STAT3 levels in isolated LE, but it also ablated implantation when injected into uterine lumen. Furthermore, AG490 treatment in wild-type animals mimics the consequences of genetic ablation of LIF that results in free floating hatched embryos, which are unable to implant. Our results support the notion that Jak2 is the sole Janus kinase to mediate LIF activation in LE, and the signaling pathways of cytokines can serve as contraception targets.

References

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Funding

No external funding was declared for this work.

Conflict of Interest

The authors declare no conflict of interest.

Ethical Approval

No ethics committee approval was required for this article type.

Data Availability

Not applicable for this article.

How to Cite This Article

Jrgang Cheng. 2016. "Chemical Inhibition of JAK2 Mimics Genetic Ablation of Uterine Function of Leukemia Inhibitory Factor". Global Journal of Medical Research - K: Interdisciplinary GJMR-K Volume 16 (GJMR Volume 16 Issue 9 (K2)).

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GJMR Volume 16 Issue 9 (K2)

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Journal Specifications

Crossref Journal DOI 10.17406/gjmra

Print ISSN 0975-5888

e-ISSN 2249-4618

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GJMR-K Classification NLMC Code: WP 440

Submission ReceivedDecember 10, 2015
Peer Review Double Blind
Handling Editor
Accepted December 31, 2015
Published March 21, 2016

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v1.2

Issue date

March 21, 2016

Language

English

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Article Matrices

Total Score: 132

Country: United States

Subject: Global Journal of Medical Research - K: Interdisciplinary

Authors: Jrgang Cheng, Colin L. Stewart (PhD/Dr. count: 0)

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