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

Min Yu, Xiandong Peng, He Li, Yining Xu, Xiaoxi Sun, Jiazhou Chen
Reproduction (Cambridge, England) · 2022 · vol. 163(3) , pp. 157–165 · doi:10.1530/rep-21-0199 · PMID:35038312 · W4205744715
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Gankyrin expression increases during mid-secretory phase and promotes embryo implantation via STAT3 activation and MMP2 expression, as demonstrated in vitro and in vivo.

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Abstract

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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Condition tags

endometriosis

MeSH descriptors

Embryo Implantation Embryo Implantation Matrix Metalloproteinase 2 Matrix Metalloproteinase 2 STAT3 Transcription Factor Transcription Factors Animals Cell Adhesion Endometrium Endometrium Female Mammals Mice STAT3 Transcription Factor Transcription Factors Trophoblasts Trophoblasts

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