Endometrial extracellular vesicles from women with recurrent implantation failure attenuate the growth and invasion of embryos

Liu, Chang; Yao, Wen; Yao, Junning; Li, Linshuang; Liu, Yang; Zhang, Hanwang; Sui, Cong

doi:10.1016/j.fertnstert.2020.04.005

Cited by 38 publications

(32 citation statements)

References 48 publications

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“…Indeed, sEVs from progesterone-primed Ishikwa cells conferred Matrigel-invading capacity to trophectoderm cells. Our findings are also supported by recent reports on endometrial EVs isolated from endometrial tissues obtained from women with recurrent implantation failure attenuating invasion of murine embryos [69]. Thus, future work would entail isolating sufficient EVs from uterine fluid and assessing their potential to confer human embryos with invasive capacity.…”

Section: Ul Proteome Provides Unique Insight Into Cycle Phase and Endometrial Receptivity: Implications For Clinical Applicationsupporting

confidence: 87%

Proteomic profiling of human uterine extracellular vesicles reveal dynamic regulation of key players of embryo implantation and fertility during menstrual cycle

et al. 2021

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Endometrial extracellular vesicles (EVs) are emerging as important players in reproductive biology. However, how their proteome is regulated throughout the menstrual cycle is not known. Such information can provide novel insights into biological processes critical for embryo development, implantation, and successful pregnancy. Using mass spectrometry-based quantitative proteomics, we show that small EVs (sEVs) isolated from uterine lavage of fertile women (UL-sEV), compared to infertile women, are laden with proteins implicated in antioxidant activity (SOD1, GSTO1, MPO, CAT).Functionally, sEVs derived from endometrial cells enhance antioxidant function in trophectoderm cells. Moreover, there was striking enrichment of invasion-related proteins (LGALS1/3, S100A4/11) in fertile UL-sEVs in the secretory (estrogen plus progesterone-driven, EP) versus proliferative (estrogen-driven, E) phase, with several players downregulated in infertile UL-sEVs. Consistent with this, sEVs from EP-versus E-primed endometrial epithelial cells promote invasion of trophectoderm cells. Interestingly, UL-sEVs from fertile versus infertile women carry known players/predictors of embryo implantation (PRDX2, IDHC), endometrial receptivity (S100A4, FGB, SER-PING1, CLU, ANXA2), and implantation success (CAT, YWHAE, PPIA), highlighting their potential to inform regarding endometrial status/pregnancy outcomes. Thus, this study provides novel insights into proteome reprograming of sEVs and soluble secretome in uterine fluid, with potential to enhance embryo implantation and hence fertility.

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Section: Ul Proteome Provides Unique Insight Into Cycle Phase and Endometrial Receptivity: Implications For Clinical Applicationsupporting

confidence: 87%

Proteomic profiling of human uterine extracellular vesicles reveal dynamic regulation of key players of embryo implantation and fertility during menstrual cycle

et al. 2021

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“…Given their fundamental role in regulating intercellular communication, it is not surprising that in some pathological contexts EVs can also play a negative role in embryo implantation. For example, endometrium-derived EVs from women with recurrent implantation failure (RIF) attenuate the growth and invasion of embryos (59). Therefore, EVs play a dual role in the process of embryo implantation, which may be attributed to the heterogeneity of EVs contents.…”

Section: Mesenchymal Stem Cell (Msc) -Derived Evsmentioning

confidence: 99%

“…It is widely accepted that women with a history of reproductive diseases such as recurrent implantation failure (RIF), polycystic ovary syndrome (PCOS), and endometriosis, are associated with future impaired embryo implantation (101)(102)(103)(104)(105). EVs-based intercellular communication plays an important role in female reproductive microenvironments and is involved in the pathogenesis of these disorders (59,89,(106)(107)(108)(109). The regulatory disorders caused by abnormal EVs may provide a new viewpoint of implantation failure in women with reproductive diseases (summarized in Table 3).…”

Section: Evs and Embryo Implantation: A New Viewpoint Of Reproductive Diseasesmentioning

confidence: 99%

“…The up-regulated miR-1246 and miR-1290 in the RIF-EVs may indicate the inadequate endometrial receptivity of RIF women (124). In vitro experimental studies have demonstrated that endometrial EVs from RIF women attenuate embryonic development and implantation capacity by inhibiting blastocyst formation, decreasing the total cell number of embryos as well as inhibiting the proliferation, migration, and invasion of trophoblast cells (59,109).…”

Section: Evs In Rifmentioning

confidence: 99%

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The Complicated Effects of Extracellular Vesicles and Their Cargos on Embryo Implantation

Jiang

2021

Front. Endocrinol.

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As a rate-limiting step in pregnancy, embryo implantation is highly dependent on intercellular communication. Extracellular vesicles (EVs) are newly identified to be important in the course of intercellular communication. EVs have been isolated from a wide variety of biofluids and tissues, including plasma, liver, uterine, semen, embryo, etc. The present and future use of EVs not only as biomarkers, but also as targeting drug delivery system, is promisingly pave the way for advanced comprehension of implantation failure in reproductive diseases. However, as the precise mechanisms of EVs in embryo implantation has not been elucidated yet. Herein, we summarize the current knowledge on the diverse effects of EVs from various sources and their cargos such as microRNA, long non-coding RNA, protein, etc. on embryo implantation, and the potential mechanisms of EVs in reproductive diseases such as recurrent implantation failure, polycystic ovary syndrome and endometriosis. It is essential to note that many of the biologically plausible functions of EVs in embryo implantation discussed in present literatures still need further research in vivo.

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“…The embryo, after all, is known to signal the endometrium through early human chorionic gonadotropin (hCG) secretion, and that signaling might be abnormal in the endometrium of endometriosis cases (5). The study by Liu et al (1) prompts the question of what function or purpose this type of signaling has in normal reproductive physiology. A question for those of us who study dysfunctional endometrium: Is there a physiologic role for endometrial EVs that turn off the embryo's ability to implant?…”

mentioning

confidence: 99%

Extracellular vesicles: a new understanding of endometrial receptivity?

Lessey

2020

Fertility and Sterility

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Endometrial extracellular vesicles from women with recurrent implantation failure attenuate the growth and invasion of embryos

Cited by 38 publications

References 48 publications

Proteomic profiling of human uterine extracellular vesicles reveal dynamic regulation of key players of embryo implantation and fertility during menstrual cycle

Proteomic profiling of human uterine extracellular vesicles reveal dynamic regulation of key players of embryo implantation and fertility during menstrual cycle

The Complicated Effects of Extracellular Vesicles and Their Cargos on Embryo Implantation

Extracellular vesicles: a new understanding of endometrial receptivity?

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