Gankyrin has a potential role in embryo implantation via activation of STAT3

in Reproduction
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Min Yu Obstetrics & Gynecology Hospital of Fudan University, Shanghai JIAI Genetics & IVF Institute, Shanghai, China

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Xiandong Peng Obstetrics & Gynecology Hospital of Fudan University, Shanghai JIAI Genetics & IVF Institute, Shanghai, China

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He Li Obstetrics & Gynecology Hospital of Fudan University, Shanghai JIAI Genetics & IVF Institute, Shanghai, China

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Yining Xu Obstetrics & Gynecology Hospital of Fudan University, Shanghai JIAI Genetics & IVF Institute, Shanghai, China

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Xiaoxi Sun Obstetrics & Gynecology Hospital of Fudan University, Shanghai JIAI Genetics & IVF Institute, Shanghai, China
Shanghai Key Laboratory of Female Reproductive and Endocrine-Related Diseases, Shanghai, China

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Jiazhou Chen Obstetrics & Gynecology Hospital of Fudan University, Shanghai JIAI Genetics & IVF Institute, Shanghai, China

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https://orcid.org/0000-0001-5591-8810

Correspondence should be addressed to J Chen; Email: veronicazhou1985@sohu.com

*(M Yu and X Peng contributed equally to this work)

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Embryo implantation, a critical step during the mammalian reproductive process, requires normal developing blastocysts and a receptive endometrium. Endometriosis, a common pathologically benign gynecological condition, is associated with decreased fertility and reduced endometrial receptivity. The oncoprotein, Gankyrin, has been associated with endometriosis and endometrial cancer. Here, we examined the role of Gankyrin during the process of embryo implantation and found that Gankyrin expression levels were significantly increased during the mid-secretory phase, but unaffected during the proliferative phase in the human endometrium. Using an in vitro cell adhesion assay to examine the cell adhesion rate of BeWo trophoblast spheroids to Gankyrin knockdown or overexpressing human endometrial carcinoma RL95-2 cells, we demonstrated that the adhesion rate was significantly reduced in Gankyrin-knockdown RL95-2 cells, while overexpression of Gankyrin promoted cell adhesion. Furthermore, we found that the downregulation of Gankyrin inhibited STAT3 activation and subsequent matrix metalloproteinase 2 (MMP2) expression, while overexpression led to STAT3 activation and MMP2 expression. In vivo, we found that Gankyrin expression was increased in the endometrium after conception but decreased with the prolongation of gestation time in female mice. siRNA-mediated knockdown of Gankyrin in the uterine horn led to a significant reduction in the number of implanted embryos 9 days post-gestation, which was associated with a decrease in p-STAT3 expression and MMP2 transcription. Taken together, our findings indicate that Gankryin has a potential role in embryo implantation via STAT3 activation.

 

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