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

Autor: Hajipour H; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Farzadi L; Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Roshangar L; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Latifi Z; Department of Biochemistry and Clinical Laboratories, Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Kahroba H; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Shahnazi V; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran., Hamdi K; Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Ghasemzadeh A; Women's Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Fattahi A; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: amirfattahi@gmail.com., Nouri M; Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: nourim@tbzmed.ac.ir.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Jun 15; Vol. 275, pp. 119351. Date of Electronic Publication: 2021 Mar 15.
DOI: 10.1016/j.lfs.2021.119351
Abstrakt: Aim: Endometrial 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.
Main Methods: Exosomes 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.
Key Findings: The isolated uterine fluid exosomes had a cup-shaped or spherical morphology with a mean size of 91.8 nm and zeta potential of -9.75 mV. The average loading capacity of exosomes for hCG was 710.05 ± 73.74 and 245.06 ± 95.66 IU/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.
Significance: These 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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