Effect of Xianziyizhen Recipe Capsule on PGI2-PPARδ Signaling Pathway in Embryo Implantation Dysfunction Mice

Am J Reprod Immunol. 2015 Jun;73(6):545-56. doi: 10.1111/aji.12361. Epub 2015 Feb 4.


Problem: We investigated the effect of Xianziyizhen recipe capsule (XRC), a kidney-tonifying herb, on the PGI2-PPARδ signaling pathway at the maternal-fetal interface in embryo implantation dysfunction (EID) mice.

Method of study: Intragastric administration of Progynova (estradiol) or XRC was performed in EID mouse model, following experimental induction of kidney deficiency by co-treatment with chemotherapy drug hydroxyurea and antiprogesterone mifepristone. The PPARδ and IL-11 mRNA expression in endometrium were detected by real-time relative reverse transcription-polymerase chain reaction (RT-PCR). Further, the protein expression of COX-2, PGI2, MMP-9, and TIMP-3 was detected in endometrial glandular epithelium and in stromal cells by immunohistochemical (IHC) assay.

Results: The results showed that hydroxyurea and mifepristone-induced EID were associated with significantly lower PPARδ and IL-11 mRNA levels in endometrium and reduced COX-2, PGI2, MMP-9, and TIMP-3 levels in endometrial glandular epithelium, compared with normal controls. However, XRC and Progynova treatment reversed these effects, leading to significant increases in PPARδ and IL-11 mRNA expression, and COX-2, PGI2, MMP-9 and TIMP-3 protein levels, when compared with the levels observed in EID mice.

Conclusion: These results strongly suggested that XRC is beneficial in EID treatment and that XRC may mediate its effects through regulation of the PGI2-PPARδ signaling pathway.

Keywords: COX-2; MMP-9; TIMP-3; Xianziyizhen recipe capsule; embryo implantation dysfunction; signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / immunology
  • Drugs, Chinese Herbal / pharmacology*
  • Embryo Implantation / drug effects*
  • Embryo Implantation / immunology
  • Endometrium / cytology
  • Endometrium / immunology*
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epoprostenol / biosynthesis
  • Epoprostenol / immunology*
  • Female
  • Interleukin-11 / biosynthesis
  • Interleukin-11 / immunology
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / immunology
  • Mice
  • Pregnancy
  • Receptors, Cytoplasmic and Nuclear / immunology*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Stromal Cells / cytology
  • Stromal Cells / immunology
  • Tissue Inhibitor of Metalloproteinase-3 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-3 / immunology


  • Drugs, Chinese Herbal
  • Interleukin-11
  • Ppard protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Tissue Inhibitor of Metalloproteinase-3
  • Epoprostenol
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse