Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Nov 2;23(21):13382.
doi: 10.3390/ijms232113382.

Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles

Hsien-Ming Wu  1 , Liang-Hsuan Chen  1 , Le-Tien Hsu  1 , Chyong-Huey Lai  1   2
Affiliations
Review

Immune Tolerance of Embryo Implantation and Pregnancy: The Role of Human Decidual Stromal Cell- and Embryonic-Derived Extracellular Vesicles

Hsien-Ming Wu et al. Int J Mol Sci. .

Abstract

Embryo-endometrial communication plays a critical role in embryo implantation and the establishment of a successful pregnancy. Successful pregnancy outcomes involve maternal immune modulation during embryo implantation. The endometrium is usually primed and immunomodulated by steroid hormones and embryo signals for subsequent embryo implantation and the maintenance of pregnancy. The roles of extracellular vesicles (EVs) and microRNAs for the embryo-maternal interactions have been elucidated recently. New evidence shows that endometrial EVs and trophectoderm-originated EV cargo, including microRNAs, proteins, and lipids in the physiological microenvironment, regulate maternal immunomodulation for embryo implantation and subsequent pregnancy. On the other hand, trophoblast-derived EVs also control the cross-communication between the trophoblasts and immune cells. The exploration of EV functions and mechanisms in the processes of embryo implantation and pregnancy will shed light on a practical tool for the diagnostic or therapeutic approaches to reproductive medicine and infertility.

Keywords: decidual stromal cell; embryo implantation; endometrium; extracellular vesicle; immunomodulation; pregnancy.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Endometrial receptivity: decidualization, immune cells, cytokines, and immune modulatory properties determine reproductive outcomes. Under the influence of progesterone, ESCs complete decidualization. The decidualized ESCs are critical to the development of surrounding trophoblastic, hematopoietic (e.g., uNK and T cell), and mesenchymal cells (e.g., blood vessels), which play an important role in blastocyst implantation. ESCs: endometrial stromal cells; uNK: uterine natural killer.
Figure 2
Figure 2
Characteristics, cargos, and functions of extracellular vesicles. The three main subtypes of extracellular vesicles (EVs) are exosomes, microvesicles (MVs), and apoptotic bodies, which are generally differentiated through size, content, and function examination. MVB: multivesicular body.
Figure 3
Figure 3
Extracellular vesicles provide intercellular communication both between embryos and endometrium. Extracellular vesicles (EVs) extend across the blastocoel and link the mural trophectoderm and inner cell mass. Trophectoderm cell line releases miRNA-containing EVs that stimulate endometrial epithelium. The communication between blastocyst and endometrium triggers successful embryo implantation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gellersen B., Reimann K., Samalecos A., Aupers S., Bamberger A.M. Invasiveness of human endometrial stromal cells is promoted by decidualization and by trophoblast-derived signals. Hum. Reprod. 2010;25:862–873. doi: 10.1093/humrep/dep468. - DOI - PubMed
    1. Blois S.M., Kammerer U., Soto C.A., Tometten M.C., Shaikly V., Barrientos G., Jurd R., Rukavina D., Thomson A.W., Klapp B.F., et al. Dendritic cells: Key to fetal tolerance? Biol. Reprod. 2007;77:590–598. doi: 10.1095/biolreprod.107.060632. - DOI - PubMed
    1. Kliman H.J., Frankfurter D. Clinical approach to recurrent implantation failure: Evidence-based evaluation of the endometrium. Fertil. Steril. 2019;111:618–628. doi: 10.1016/j.fertnstert.2019.02.011. - DOI - PubMed
    1. Evans J., Salamonsen L.A., Winship A., Menkhorst E., Nie G., Gargett C.E., Dimitriadis E. Fertile ground: Human endometrial programming and lessons in health and disease. Nat. Rev. Endocrinol. 2016;12:654–667. doi: 10.1038/nrendo.2016.116. - DOI - PubMed
    1. Ashary N., Tiwari A., Modi D. Embryo Implantation: War in Times of Love. Endocrinology. 2018;159:1188–1198. doi: 10.1210/en.2017-03082. - DOI - PubMed

LinkOut - more resources