1. Academic Validation
  2. Estradiol promotes trophoblast viability and invasion by activating SGK1

Estradiol promotes trophoblast viability and invasion by activating SGK1

  • Biomed Pharmacother. 2019 Sep;117:109092. doi: 10.1016/j.biopha.2019.109092.
Wei-Hua He 1 Meng-Meng Jin 2 Ai-Ping Liu 3 Ying Zhou 4 Xiao-Ling Hu 5 Yi-Min Zhu 6 Ai-Xia Liu 7
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, First Affiliated Hospital, Zhejiang University College of Medicine, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, PR China. Electronic address: molihua505@163.com.
  • 2 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, PR China. Electronic address: 3110103602@zju.edu.cn.
  • 3 Department of Surgery, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI, 53705, USA. Electronic address: aipingsmile@gmail.com.
  • 4 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, PR China. Electronic address: 21818423@zju.edu.cn.
  • 5 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, PR China. Electronic address: xiaolinghu1982@163.com.
  • 6 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, PR China; Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, 310006, PR China. Electronic address: zhuyim@zju.edu.cn.
  • 7 Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, PR China; Key Laboratory of Reproductive Genetics (Ministry of Education), Zhejiang University, Hangzhou, 310006, PR China. Electronic address: liuaixia@zju.edu.cn.
Abstract

Background: 17β-Estradiol (E2) is a critical regulator of trophoblast function during pregnancy. Serum- and glucocorticoid-inducible kinase (SGK1) has been shown to regulate specific cellular targets downstream of E2. However, whether and how SGK1 directly mediates the regulatory effects of E2 on trophoblasts functions remain unknown.

Methods: SGK1 expression in human villous samples and serum E2 levels were measured in women with early pregnancy loss (EPL) and healthy pregnant women. The effect of E2 on SGK1 regulation was assessed using luciferase reporter gene assay and Chromatin Immunoprecipitation assay. The mediation of regulatory effects of E2 by SGK1 on trophoblast functions including cell viability, invasion and related signaling molecules such as B cell leukemia/lymphoma 6, E-cadherin, matrix metalloproteinase 2, α-ENaC, vascular endothelial growth factor, and the phosphorylation status of FOXO1 and Akt were evaluated in HTR8/SVneo cells transfected with SGK1 knockdown plasmid with/without E2 treatment.

Results: SGK1 protein levels in human villous samples and serum E2 levels were decreased in patients with EPL compared to controls. E2 (10 nM) increased SGK1 promoter activity directly through Estrogen Receptor. E2-activated SGK1 enhanced cell viability, invasion and downstream targets in trophoblast cells. SGK1 knockdown abrogated the above responses to E2 treatment.

Conclusions: SGK1 mediates the effects of E2 on trophoblast viability and invasion, suggesting that SGK1 acts as a key node in regulating the cross-talk at the feto-maternal interface during the development of placenta and might be a potential therapeutic target for EPL.

Keywords

Estradiol; Invasion; SGK1; Trophoblast; Viability.

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