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

• Published in: American journal of reproductive immunology (1989) 2015-06, Vol.73 (6), p.545-556
• Main Authors: Xu, Min, Tian, Ying-Zhou, Zhu, Xiu-Jun, Zhang, Xi, Zhu, Jing-Yan, Gu, Chun-Xiao, Chen, Yi, Huang, Jian-Ling
• Format: Article
• Language: English
• Subjects: Animals; COX-2; Cyclooxygenase 2 - biosynthesis; Cyclooxygenase 2 - immunology; Drugs, Chinese Herbal - pharmacology; Embryo Implantation - drug effects; Embryo Implantation - immunology; embryo implantation dysfunction; 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; MMP-9; Pregnancy; Receptors, Cytoplasmic and Nuclear - immunology; Receptors, Cytoplasmic and Nuclear - metabolism; signal transduction; Stromal Cells - cytology; Stromal Cells - immunology; TIMP-3; Tissue Inhibitor of Metalloproteinase-3 - biosynthesis; Tissue Inhibitor of Metalloproteinase-3 - immunology; Xianziyizhen recipe capsule
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.12361

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.