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The Pre-Implantation Embryo Induces Uterine Inflammatory Reaction in Mice

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Abstract

It has been well established that uterine function during the peri-implantation period is precisely regulated by ovarian estrogen and progesterone. The embryo enters the uterine cavity before implantation. However, the impact of pre-implantation embryo on uterine function is largely unknown. In the present study, we performed RNA-seq analysis of mouse uterus on day 4 morning of natural pregnancy (with embryos in the uterus) and pseudo-pregnancy (without embryos in the uterus). We found that 146 genes were upregulated, and 77 genes were downregulated by the pre-implantation embryo. Gene ontology and gene network analysis highlighted the activation of inflammatory reaction in the uterus. By examining the promoter region of differentially expressed genes, we found that NF-kappaB was a causal transcription factor. Finally, we validated 4 inflammation-related genes by quantitative RT-PCR. These 4 genes are likely the main mediators of the inflammatory reaction in the uterus triggered by the pre-implantation embryo. Our data indicated that the pre-implantation embryo causes uterine inflammatory reaction, which in turn might contribute to the establishment of uterine receptivity and embryo implantation.

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Funding

This work was funded by National Natural Science Foundation of China (31771665), Guangdong Special Support Program (2019BT02Y276), and Innovation Team Project of Guangdong University (2019KCXTD001). The funders have no role in study design, data collection, analysis or interpretation.

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Authors and Affiliations

  1. College of Veterinary Medicine, South China Agricultural University, No.483 Wushan Road, Tianhe District, Guangzhou, 510642, China

    Can Zhu, Miao Zhao, Ming-Yu Huang, Hao-Zhuang Cheng, Jia-Peng He & Ji-Long Liu

  2. Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou, China

    Can Zhu, Miao Zhao, Ming-Yu Huang, Hao-Zhuang Cheng, Jia-Peng He & Ji-Long Liu

  3. College of Life Sciences and Resource Environment, Yichun University, Yichun, 336000, China

    Wei Hu

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  1. Can Zhu
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Zhu, C., Hu, W., Zhao, M. et al. The Pre-Implantation Embryo Induces Uterine Inflammatory Reaction in Mice. Reprod. Sci. 28, 60–68 (2021). https://doi.org/10.1007/s43032-020-00259-7

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