Expression of ENPP3 in human cyclic endometrium: a novel molecule involved in embryo implantation
Qianqian Chen A , Aijie Xin B , Ronggui Qu B , Wenbi Zhang B , Lu Li B , Junling Chen B , Xiang Lu B , Yongwei Gu A , Jing Li A and Xiaoxi Sun A B C D
+ Author Affiliations
- Author Affiliations
A Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
B Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
C Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
D Corresponding author. Email: xiaoxi_sun@aliyun.com
Reproduction, Fertility and Development 30(10) 1277-1285 https://doi.org/10.1071/RD17257
Submitted: 8 July 2017 Accepted: 4 March 2018 Published: 4 April 2018
Abstract
Ectonucleotide pyrophosphatase–phosphodiesterase 3 (ENPP3), a protein detected in the human uterus, has been found to play an important role in the development and invasion of tumours. It was recently discovered that ENPP3 was upregulated during the window of implantation in the human endometrium but its functional relevance remains elusive. The objective was to determine ENPP3 expression in human endometrium and its roles in endometrial receptivity and embryo implantation. ENPP3 expression was analysed using immunohistochemistry and western blot assay. The effects of ENPP3 on embryo implantation were evaluated using a BeWo cell (a human choriocarcinoma cell line) spheroid attachment assay and BeWo cells were dual cultured with Ishikawa cells transfected with lentiviral vectors (LV5-NC or LV5-ENPP3) to mimic embryo implantation in a Transwell model. The effects of endometrial ENPP3 on factors related to endometrial receptivity were also determined. The results showed that ENPP3 was expressed in human endometrial epithelial cells and its expression levels changed during the menstrual cycle, peaking in the mid-secretory phase, corresponding to the time of embryo implantation. The overexpression of endometrial ENPP3 not only increased the embryo implantation rate but also had positive effects on the expression of factors related to endometrial receptivity in human endometrial cells. The results indicate that ENPP3 levels undergo cyclic changes in the endometrium and affect embryo adhesion and invasion via altering the expression of implantation factors in the human endometrium. Therefore, ENPP3 may play an important role in embryo implantation and may be a unique biomarker of endometrial receptivity.
Additional keywords: endometrial receptivity, integrin-β3, LIF, window of implantation.
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