Extracellular vesicles in embryo implantation and disorders of the endometrium

Mishra, Anuradha; Ashary, Nancy; Sharma, Richa; Modi, Deepak

doi:10.1111/aji.13360

Cited by 32 publications

(20 citation statements)

References 116 publications

(336 reference statements)

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“…EVs have been reported to mediate cell–cell communication and modulate numerous biological processes, including endometrial receptivity, which is essential in embryo implantation [ 62 ]. Here, we isolated goat UFs’ EVs and validated them through TEM, NTA, and Western blotting.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression Pattern of Goat Uterine Fluids Extracellular Vesicles miRNAs during Peri-Implantation

Xie

Liu

Zang

et al. 2021

Cells

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Early pregnancy failure occurs when a mature embryo attaches to an unreceptive endometrium. During the formation of a receptive endometrium, extracellular vesicles (EVs) of the uterine fluids (UFs) deliver regulatory molecules such as small RNAs to mediate intrauterine communication between the embryo and the endometrium. However, profiling of small RNAs in goat UFs’ EVs during pregnancy recognition (day 16) has not been carried out. In this study, EVs were isolated from UFs on day 16 of the estrous cycle or gestation. They were isolated by Optiprep™ Density G radient (ODG) and verified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Immunostaining demonstrated that CD63 was present both in the endometrial epithelium and glandular epithelium, and stain intensity was greater in the pregnant endometrium compared to the non-pregnant endometrium. Small RNA sequencing revealed that UFs’ EVs contained numerous sRNA families and a total of 106 differentially expressed miRNAs (DEMs). Additionally, 1867 target genes of the DEMs were obtained, and miRNA–mRNA interaction networks were constructed. GO and KEGG analysis showed that miRNAs were significantly associated with the formation of a receptive endometrium and embryo implantation. In addition, the fluorescence in situ hybridization assay (FISH) showed that chi-miR-451-5p was mainly expressed in stromal cells of the endometrium and a higher level was detected in the endometrial luminal epithelium in pregnant states. Moreover, the dual-luciferase reporter assay showed that chi-miR-451-5p directly binds to PSMB8 and may play an important role in the formation of a receptive endometrium and embryo implantation. In conclusion, these results reveal that UFs’ EVs contain various small RNAs that may be vital in the formation of a receptive endometrium and embryo implantation.

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Section: Discussionmentioning

confidence: 99%

Differential Expression Pattern of Goat Uterine Fluids Extracellular Vesicles miRNAs during Peri-Implantation

Xie

Liu

Zang

et al. 2021

Cells

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“…Recent data suggest that EVs play a key role in these complex processes 109‐111 . EVs that contribute to bidirectional maternal‐embryo communication during preimplantation/implantation may emanate from the blastocyst's inner cell mass and trophectoderm and from the maternal oviduct, endometrial lining, endometrial stroma, and more distant tissues 109,112‐121 . Indeed, local bidirectional EV‐mediated communication between blastocyst cells and recipient endometrium is believed to modulate maternal immune response and to prepare the trophectoderm cells for interaction with the endometrial epithelium 122,123 …”

Section: Placental‐maternal‐fetal Ev Trafficking Patterns During Preg...mentioning

confidence: 99%

Extracellular vesicles and immune response during pregnancy: A balancing act*

Morelli

Sadovsky

2022

Immunological Reviews

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A healthy pregnancy represents an immunological paradox, first described by Peter Medawar, in which the fetus is not rejected by the maternal immune system. 1 Indeed, the feto-placental unit constitutes a semi-allogeneic graft within the maternal host, where typically maternal T and B lymphocytes have not been previously exposed to and tolerized by the expression of paternal antigens (Ags).The paradox is heightened when pregnancy results from a sperm and a donor oocyte, or in a surrogate pregnancy, where the fetus is a full allograft. The intricate immune-regulatory mechanisms that operate at the fetal-maternal interface and in the mother's lymphoid organs and avert the maternal immunologic attack on feto-placental tissues while maintaining immune homeostasis and maternal competent defense against pathogens remain largely unknown. 2 Complex developmental processes underlie the development of the embryonic immune system. 3 As the immune interactions evolve, multiple tolerance-promoting mechanisms become active at the

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“…The endometrium is proposed to have a mechanism to screen embryo quality prior to implantation [ 130 ], and EVs secreted by embryos have been suggested as the mediator where the cargo in the EVs is exposed to and assessed by the endometrium for embryo quality [ 130 ]. Embryonic EVs have been suggested to epigenetically regulate endometrial cells via EV-mediated RNA transfer, and poor embryos are unable to establish the same epigenetic changes [ 131 ].…”

Section: Micrornas and Endometrial Receptivitymentioning

confidence: 99%

“…There is growing evidence suggesting that the endometrium also has an active role in selecting embryonic EVs based on the cargo profile, which could include miRNAs such as the let-7 family, miR-31, miR-101a, miR-199a, miR-200 and the aforementioned miR-661 [ 121 , 132 ]. Other studies have predicted that miRNAs derived from the blastocyst culture medium may potentially modulate endometrial epithelial proliferation and embryo attachment [ 31 , 130 , 133 ].…”

Section: Micrornas and Endometrial Receptivitymentioning

confidence: 99%

MicroRNAs in the Regulation of Endometrial Receptivity for Embryo Implantation

Shekibi

Heng

Nie

2022

IJMS

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Development of endometrial receptivity is crucial for successful embryo implantation and pregnancy initiation. Understanding the molecular regulation underpinning endometrial transformation to a receptive state is key to improving implantation rates in fertility treatments such as IVF. With microRNAs (miRNAs) increasingly recognized as important gene regulators, recent studies have investigated the role of miRNAs in the endometrium. Studies on miRNAs in endometrial disorders such as endometriosis and endometrial cancer have been reviewed previously. In this minireview, we aim to provide an up-to-date knowledge of miRNAs in the regulation of endometrial receptivity. Since endometrial remodelling differs considerably between species, we firstly summarised the key events of the endometrial cycle in humans and mice and then reviewed the miRNAs identified so far in these two species with likely functional significance in receptivity establishment. To date, 29 miRNAs have been reported in humans and 15 miRNAs in mice within various compartments of the endometrium that may potentially modulate receptivity; miRNAs regulating the Wnt signalling and those from the let-7, miR-23, miR-30, miR-200 and miR-183 families are found in both species. Future studies are warranted to investigate miRNAs as biomarkers and/or therapeutic targets to detect/improve endometrial receptivity in human fertility treatment.

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Extracellular vesicles in embryo implantation and disorders of the endometrium

Cited by 32 publications

References 116 publications

Differential Expression Pattern of Goat Uterine Fluids Extracellular Vesicles miRNAs during Peri-Implantation

Differential Expression Pattern of Goat Uterine Fluids Extracellular Vesicles miRNAs during Peri-Implantation

Extracellular vesicles and immune response during pregnancy: A balancing act*

MicroRNAs in the Regulation of Endometrial Receptivity for Embryo Implantation

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