A human chorionic gonadotropin (hCG) delivery platform using engineered uterine exosomes to improve endometrial receptivity.

Abstract

AIM\nEndometrial exosomes carry bioactive agents to uterine epithelial cells and trophectoderm to promote implantation. On the other hand, intrauterine administration of human chorionic gonadotropin (hCG) could improve endometrial receptivity. Therefore, we investigated the delivery of hCG to the endometrial cells by uterine exosomes to increase endometrial receptivity.\n\n\nMAIN METHODS\nExosomes were isolated from uterine fluid and characterized by dynamic light scattering, transmission electron microscopy, and western blotting. The freeze-thaw cycle and sonication methods were used to load hCG into the exosomes. The drug release pattern and uptake of exosomes into the endometrial cells were evaluated. Finally, the influence of hCG loaded-exosomes on the expression of several endometrial receptivity markers was evaluated.\n\n\nKEY FINDINGS\nThe isolated uterine fluid exosomes had a cup-shaped or spherical morphology with a mean size of 91.8\u202fnm and zeta potential of -9.75\u202fmV. The average loading capacity of exosomes for hCG was 710.05\u202f±\u202f73.74 and 245.06\u202f±\u202f95.66\u202fIU/mg using the sonication and freeze-thaw cycle methods, respectively. The effect of hCG loaded-exosomes on the endometrial receptivity was greater than the hCG or exosomes alone. We found that hCG upregulated LIF and Trophinin and downregulated Muc-16 and IGFBP1 genes. Interestingly, the effect of hCG on the expression of LIF and Muc-16 was significantly intensified when used in the form of hCG loaded-exosomes.\n\n\nSIGNIFICANCE\nThese findings strengthen our hope in using uterine fluid-derived exosome as an effective carrier for proteins or other therapeutic agents to effective delivery into endometrial cells.