Effects of GnRH antagonist on endometrial protein profiles in the window of implantation

Authors

  • Yan Meng,

    1. State key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China
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    • These authors contributed equally to the work.

  • Yueshuai Guo,

    1. State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, P. R. China
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    • These authors contributed equally to the work.

  • Yi Qian,

    1. State key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China
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  • Xuejiang Guo,

    1. State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, P. R. China
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  • Li Gao,

    1. State key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China
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  • Jiahao Sha,

    1. State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, P. R. China
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  • Yugui Cui,

    1. State key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China
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  • Ri-Cheng Chian,

    1. State key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China
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  • Jiayin Liu

    Corresponding author
    1. State key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P. R. China
    • Correspondence: Dr. Jiayin Liu, State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P. R. China

      E-mail: Liu-Jiayin2014@hotmail.com

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Abstract

GnRH antagonists can suppress luteinizing hormone and follicle-stimulating hormone (FSH), with less initial stimulatory effect and lower risk of ovarian hyperstimulation syndrome. The effects of GnRH antagonists on embryonic implantation remain controversial. To evaluate the effects of GnRH antagonists, endometrial tissues were biopsied from 12 women with intracytoplasmic sperm injection treatment, in which four subjects undergoing controlled ovulation stimulation with rFSH and GnRH antagonist, four subjects with a GnRH agonist long protocol, and four natural cycle controls. After iTRAQ quantification analysis, 24 proteins showed differential expression between natural cycle and agonist treatment group and 39 proteins between natural cycle and antagonist treatment group. A total of seven proteins demonstrated differential expression only in antagonist treatment group. Bioinformatic analysis implied these proteins can function in cell processes including angiogenesis, cell proliferation, apoptosis, cell migration, and immune response. Furthermore, GnRH antagonist suppressed the function of GNAS and ANPEP, which were important for endometrial functions. Immunohistochemical staining showed that ANPEP was mainly localized in the human endometrial stroma, while ACO2, CDC5L, and GNAS were mainly localized in the glands. This study could provide insights into the effect of GnRH antagonists on the endometrium, and help optimize the embryo implantation and improve the success rate for GnRH antagonist protocol.

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