Engineered exosome as a biological nanoplatform for drug delivery of Rosmarinic acid to improve implantation in mice with induced endometritis

Abstract

Endometritis is an inflammatory and histopathologic disease in uterine tissues that interferes with the proper decidualization and implantation of the embryo. In this study, rosmarinic acid (RA) is used as an anti-inflammatory agent that encapsulates in exosomes and is used to attenuate lipopolysaccharide (LPS)-induced endometritis and improve implantation. For this purpose, exosomes were loaded with RA and then administrated into the animal groups, including RA, exosome, RA plus exosome (RA + Exo), and RA-loaded exosomes (RALExo) groups. The concentrations of RA or exosomes used in this study were 10 mg/kg, and the compounds were injected into the uterine horn 24 h following the induction of endometritis. Upon the presence of inflammation detected by the histopathological method, the most proper groups were mated with male mice. The effect of the treatment group on the implantation rate, progesterone levels, and gene expressions were assessed by Chicago Blue staining, enzyme-linked immunosorbent assay (ELISA), and Quantitative PCR (qPCR), respectively. Results showed RALExo10 and RA10 + Exo10 groups improved pathological alterations, enhanced progesterone levels, increased implantation rate, as well as heightened expression levels of Leukemia inhibitory factor (LIF) and Mucin-16 (MUC-16) genes. Besides, the expression levels of inflammatory cytokines, including Transforming growth factor-β (TGF-β), Interlukine-10 (IL-10), Interlukine-15 (IL-15), and Interlukine-18 (IL-18), were regulated. Our findings indicated that the expression of LIF, Muc-16 genes as well as IL-18, were significantly correlated with serum progesterone concentrations and the implantation rate in the treatment groups. The RALExo10 and RA10 + Exo10 groups showed ameliorated implantation rates in experimental groups.

Keywords:

• Endometritis
• exosome
• implantation
• Rosmarinic acid
• drug delivery

Acknowledgments

The authors thank Drug Applied Research Center, Tabriz University of Medical Sciences and Faculty of Veterinary Medicine, university of Tabriz, Tabriz, Iran, for scientific support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Designed the experiments and taken the data and wrote the manuscript: MT; writing and editing the manuscript and planned experiments and ideas presented: RA; helped in gene expression analysis and data analysis: RJJ; conducted experimental design and revised the manuscript: AF; helped in pathological analysis: MKH; revised the manuscript and helped in drug loading procedure: HH. All authors have read the manuscript and approved to submit it to your journal.

Data availability statement

Data available upon request of the authors.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was not funded by any specific grant from any funding agency in the public or sectors.