C-X-C Chemokine Receptor Type 4 (CXCR-4) Selective Allosteric Agonist ATI2341 TFA Promotes Uterine Repair in Asherman Syndrome

Abstract

Our study elucidated the therapeutic effect and mechanism of CXCR4 functional selective allosteric agonist ATI2341 TFA on treating Asherman syndrome (AS). AS was established by damaging mouse uterus and the bone marrow cells from ubiquitin-GFP mice were transplanted into AS mice. After 2 weeks, PBS, CXCR4 agonist ATI2341 TFA, CXCR4 antagonist or combined drugs were administrated into mice followed by analysis of detect pregnancy rate, litter size and pregnancy cycle. In AS model, ATI2341 TFA administration promoted BMSCs recruitment into uterine, which was inhibited by CXCL12 receptor antagonist ADM3100. In addition, ATI2341 TFA administration mitigated the degree of endometrial fibrosis, which was exacerbated by ADM3100. ATI2341 TFA administration also improved the fertility and the number of litter and shorten the pregnancy cycle of mice, while ADM3100 exhibited the opposite impacts. In conclusion, CXCR4 receptor agonist alleviates the infertility or adverse pregnancy outcomes possibly through promoting the recruitment of BMSCs in AS mice.