Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure

Recurrent implantation failure (RIF) is defined as failure to achieve clinical pregnancy after at least 3 transfers of good-quality embryos by natural or artificial means. RIF is often a complex problem with a wide variety of etiologies and mechanisms as well as treatment options. In this study, us...

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Main Authors: Haixia Li, Ning Sun, Yaqiao Zhu, Wei Wang, Meihong Cai, Xiaohuan Luo, Wei Xia, Song Quan
Format: Article
Language:English
Published: PAGEPress Publications 2022-12-01
Series:European Journal of Histochemistry
Subjects:
Online Access:https://ejh.it/index.php/ejh/article/view/3580
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author Haixia Li
Ning Sun
Yaqiao Zhu
Wei Wang
Meihong Cai
Xiaohuan Luo
Wei Xia
Song Quan
author_facet Haixia Li
Ning Sun
Yaqiao Zhu
Wei Wang
Meihong Cai
Xiaohuan Luo
Wei Xia
Song Quan
author_sort Haixia Li
collection DOAJ
description Recurrent implantation failure (RIF) is defined as failure to achieve clinical pregnancy after at least 3 transfers of good-quality embryos by natural or artificial means. RIF is often a complex problem with a wide variety of etiologies and mechanisms as well as treatment options. In this study, using immunohistochemistry and Western blot, we demonstrated that the expression of leukemia inhibitory factor (LIF), Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) was increased, while that of suppressor of cytokine signaling 1 (SOCS1) was decreased in RIF patients. Growth hormone (GH) administration proved to have positive effects on embryo implantation in RIF patients, but the action mechanism of GH has not been elucidated yet. To this aim, we studied the effects of GH on the proliferation in vitro of endometrial adenocarcinoma Ishikawa cells. GH stimulated the expression of LIF and SOCS1, and through SOCS1 inhibits the expression of phosphorylated STAT3, and finally inhibits the occurrence of RIF. Excessive phosphorylation of STAT can lead to decreased endometrial receptivity and abnormal embryo implantation. We also examined the effects of LIF overexpression and an LIF inhibitor (EC330) on the JAK/STAT pathway. LIF promoted cell proliferation, and the up-regulation of LIF increased the expression of SOCS1 and JAK1/STAT3 pathway-related genes in Ishikawa cells. As GH can inhibit the JAK1/STAT3 pathway through LIF, we hypothesize that upregulating SOCS1 may be a potential approach to treat RIF at the molecular level. GH can inhibit the JAK1/STAT3 pathway through LIF, up-regulating SOCS1 to treat RIF at the molecular level.
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spelling doaj.art-a814ca132ecb4e8790d3a3cc1833e8ad2022-12-22T14:52:45ZengPAGEPress PublicationsEuropean Journal of Histochemistry1121-760X2038-83062022-12-0167110.4081/ejh.2023.3580Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failureHaixia Li0Ning Sun1Yaqiao Zhu2Wei Wang3Meihong Cai4Xiaohuan Luo5Wei Xia6Song Quan7Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, GuangzhouDepartment of Reproductive Medicine Centre, Guangzhou First People's Hospital, South China University of Technology, GuangzhouDepartment of Reproductive Medicine Centre, Guangzhou First People's Hospital, South China University of Technology, GuangzhouDepartment of Reproductive Medicine Centre, Guangzhou First People's Hospital, South China University of Technology, GuangzhouDepartment of Reproductive Medicine Centre, Guangzhou First People's Hospital, South China University of Technology, GuangzhouDepartment of Reproductive Medicine Centre, Guangzhou First People's Hospital, South China University of Technology, GuangzhouDepartment of Reproductive Medicine Centre, Guangzhou First People's Hospital, South China University of Technology, GuangzhouCenter for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou Recurrent implantation failure (RIF) is defined as failure to achieve clinical pregnancy after at least 3 transfers of good-quality embryos by natural or artificial means. RIF is often a complex problem with a wide variety of etiologies and mechanisms as well as treatment options. In this study, using immunohistochemistry and Western blot, we demonstrated that the expression of leukemia inhibitory factor (LIF), Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) was increased, while that of suppressor of cytokine signaling 1 (SOCS1) was decreased in RIF patients. Growth hormone (GH) administration proved to have positive effects on embryo implantation in RIF patients, but the action mechanism of GH has not been elucidated yet. To this aim, we studied the effects of GH on the proliferation in vitro of endometrial adenocarcinoma Ishikawa cells. GH stimulated the expression of LIF and SOCS1, and through SOCS1 inhibits the expression of phosphorylated STAT3, and finally inhibits the occurrence of RIF. Excessive phosphorylation of STAT can lead to decreased endometrial receptivity and abnormal embryo implantation. We also examined the effects of LIF overexpression and an LIF inhibitor (EC330) on the JAK/STAT pathway. LIF promoted cell proliferation, and the up-regulation of LIF increased the expression of SOCS1 and JAK1/STAT3 pathway-related genes in Ishikawa cells. As GH can inhibit the JAK1/STAT3 pathway through LIF, we hypothesize that upregulating SOCS1 may be a potential approach to treat RIF at the molecular level. GH can inhibit the JAK1/STAT3 pathway through LIF, up-regulating SOCS1 to treat RIF at the molecular level. https://ejh.it/index.php/ejh/article/view/3580Recurrent implantation failureJAK/STAT pathwayleukemia inhibitory factorgrowth hormoneSOCS1
spellingShingle Haixia Li
Ning Sun
Yaqiao Zhu
Wei Wang
Meihong Cai
Xiaohuan Luo
Wei Xia
Song Quan
Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure
European Journal of Histochemistry
Recurrent implantation failure
JAK/STAT pathway
leukemia inhibitory factor
growth hormone
SOCS1
title Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure
title_full Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure
title_fullStr Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure
title_full_unstemmed Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure
title_short Growth hormone inhibits the JAK/STAT3 pathway by regulating SOCS1 in endometrial cells <em>in vitro</em>: a clue to enhance endometrial receptivity in recurrent implantation failure
title_sort growth hormone inhibits the jak stat3 pathway by regulating socs1 in endometrial cells em in vitro em a clue to enhance endometrial receptivity in recurrent implantation failure
topic Recurrent implantation failure
JAK/STAT pathway
leukemia inhibitory factor
growth hormone
SOCS1
url https://ejh.it/index.php/ejh/article/view/3580
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