Found programs: Open Project of Henan Key Laboratory of Immunology and Targeted Drugs （ No. HNKLITD2024001）；Open Project of State Key Laboratory of Pathogenesis，Prevention and Treatment of High In- cidence Diseases in Central Asia（No. SKL-HIDCA-2024- GX2）；Innovative Research Project of Xinjiang Uygur Autonomous Region Health and Wellness，Science and Technology Program（No. 2025001CXKYXM650030870 ）
Authors：Wang Peng1，Gong Xiaoyun1，Zhang Manli1，Zhang Yunian1，La Xiaolin1，2，3，4
Keywords：follicular helper T cells；embryo implantation disorder；C-X-C chemokine receptor type 5 protein；B- cell lymphoma 6 protein；cytokines；endometrial receptivity
DOI：10.19405/j.cnki.issn1000-1492.2026.01.007
〔Abstract〕 To detect the proportion of splenic follicular helper T（Tfh）cells and their functionally re- lated cytokine expression levels in the incomplete embryo implantation disorder（EID）model mice，and to explore the immunological mechanism of Tfh in infertility caused by embryo implantation disorder. Methods Sixteen fe- male Kunming mice were randomly divided into two groups，with eight mice in each group. On day 4 of pregnancy， an incomplete EID mouse model was established by oral gavage of mifepristone suspension，while an equal volume of saline was administered to the control group. On day 8 of pregnancy，the mice were euthanized. Flow cytometry was used to detect the levels of Tfh cells in the spleen lymphocytes of both incomplete EID mice and normal control mice. qRT-PCR was performed to measure the mRNA levels of B-cell lymphoma 6（Bcl-6）and C-X-C chemokine receptor type 5 protein（CXCR5）in the spleen lymphocytes of both groups. Western blot was employed to assess the protein expression levels of Bcl-6 and CXCR5 in the spleen lymphocytes of both groups. Serum levels of inter- leukin-4（IL-4）， IL-6，and IL-21 were measured by ELISA. Immunohistochemistry（IHC）was used to observe the expression levels of progesterone receptor（PR），Bcl-6，and CXCR5 proteins in the uterine endometrial tissue of mice in both groups. Results Incomplete-type EID mice had a reduced number of embryo implantation points and reduced endometrial PR expression. Flow assay results showed that the proportion of CD4+CXCR5+Tfh cells in splenic lymphocytes of incomplete-type EID mice was significantly higher than that of normal controls（P<0. 05）.Compared with the normal control group，Bcl-6 and CXCR5 mRNA levels and protein levels were elevated in splenic lymphocytes of incomplete EID mice，with statistically significant differences（P<0. 05）；serum IL-4，IL- 6，and IL-21 levels were elevated in incomplete EID mice，and Bcl-6 and CXCR5 proteins in the endometrium were significantly elevated（P<0. 05）. Conclusion The increase of Tfh cells and their associated cytokines Bcl-6 and CXCR5 is associated with the development of incomplete EID，and may be involved in the development of fe- male immune infertility.