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Expression of SGLT1 in the Mouse Endometrial Epithelium and its Role in Early Embryonic Development and Implantation

  • Reproductive Biology: Original Article
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Abstract

Many functional activities of endometrium epithelium are energy consuming which are very important for maintaining intrauterine environment needed by early embryonic development and establishment of implantation window. Glucose is a main energy supplier and one of the main components of intrauterine fluid. Obviously, glucose transports in endometrium epithelium involve in for these activities but their functions have not been elucidated. In this research, we observed a spatiotemporal pattern of sodium glucose transporter 1 (SGLT1) expression in the mouse endometrium. We also determined that progesterone can promote the expression of SGLT1 in the mouse endometrial epithelium in response to the action of oestrogen. Treatment with the SGLT1 inhibitor phlorizin or small interfering RNA specific for SGLT1 (SGLT1-siRNA) altered glucose uptake in primary cultured endometrial epithelial cells, which exhibited reduced ATP levels and AMPK activation. The injection of phlorizin or SGLT1-siRNA into one uterine horn of each mouse on day 2 of pregnancy led to an increased glucose concentration in the uterine fluid and decreased number of harvested normal blastocysts and decreased expression of integrin αVβ3 in endometrial epithelium and increased expression of mucin 1 and lactoferrin in endometrial epithelium and the uterine homogenates exhibited activated AMPK, a decreased ATP level on day 4, and a decreased number of implantation sites on day 5. In embryo transfer experiments, pre-treatment of the uterine horn with phlorizin or SGLT1-siRNA during the implantation window led to a decreased embryo implantation rate on day 5 of pregnancy, even when embryos from normal donor mice were used. In conclusion, SGLT1, which participates in glucose transport in the mouse endometrial epithelium, inhibition and/or reduced expression of SGLT1 affects early embryo development by altering the glucose concentration in the uterine fluid. Inhibition and/or reduced expression of SGLT1 also affects embryo implantation by influencing energy metabolism in epithelial cells, which consequently influences implantation-related functional activities.

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Acknowledgements

The authors gratefully acknowledge the support from the National Natural Science Foundation of China (No.31471105 and No.31900822, URL: http://www.nsfc.gov.cn/). Support from Sichuan Science and Technology Program (No.2020YJ0486, URL: http://202.61.89.120/). Support from the Fundamental Research Funds for the Central Universities from Northwest Minzu University (No.31920180028).

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Authors and Affiliations

  1. Department of Physiology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, No. 17 Section 3 Renmin South Road, Chengdu, 610041, People’s Republic of China

    Li-xue Zhang, Jia-wei Song, Yong-dan Ma, Yi-cheng Wang, Zhi-hui Cui, Yun Long, Dong-zhi Yuan, Jin-hu Zhang, Li Nie & Li-min Yue

  2. School of Medicine, Northwest Minzu University, Lanzhou, 730030, China

    Li-xue Zhang

  3. Reproductive Endocrinology and Regulation Joint Laboratory, West China Second University Hospital, Sichuan University, Chengdu, 610041, China

    Ying Hu & Li-min Yue

  4. Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, China

    Lin-lin Yu

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Zhang, Lx., Song, Jw., Ma, Yd. et al. Expression of SGLT1 in the Mouse Endometrial Epithelium and its Role in Early Embryonic Development and Implantation. Reprod. Sci. 28, 3094–3108 (2021). https://doi.org/10.1007/s43032-021-00480-y

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