PMID- 34803505 OWN - NLM STAT- MEDLINE DCOM- 20211220 LR - 20231213 IS - 1449-2288 (Electronic) IS - 1449-2288 (Linking) VI - 17 IP - 15 DP - 2021 TI - Extracellular Vesicle-Mediated Secretion of HLA-E by Trophoblasts Maintains Pregnancy by Regulating the Metabolism of Decidual NK Cells. PG - 4377-4395 LID - 10.7150/ijbs.63390 [doi] AB - Extracellular vesicles derived from trophoblasts (T-EVs) play an important role in pregnancy, but the mechanism is not entirely clear. In this study, we found that HLA-E, which is mostly confined to the cytoplasm of trophoblast cells, was secreted by T-EVs. The level of HLA-E in T-EVs from unexplained recurrent spontaneous abortion (URSA) patients was lower than that in normal pregnancy (NP) and RSA patients who had an abnormal embryo karyotype (AK-RSA). T-EVs promoted secretion of IFN-gamma and VEGFalpha by decidual NK (dNK) cells from URSA patients via HLA-E, VEGFalpha was necessary for angiogenesis and trophoblast growth, and IFN-gamma inhibited Th17 induction. Glycolysis and oxidative phosphorylation (OxPhos) were involved in this process. Glycolysis but not OxPhos of dNK cells facilitated by T-EVs was dependent on mTORC1 activation. Inhibition of T-EV production in vivo increased the susceptibility of mice to embryo absorption, which was reversed by transferring exogenous T-EVs. T-EVs promoted secretion of IFN-gamma and VEGFalpha by dNK cells to maintain pregnancy via Qa-1 in abortion-prone mouse models. This study reveals a new mechanism of pregnancy maintenance mediated by HLA-E via T-EVs. CI - (c) The author(s). FAU - Jiang, Lingling AU - Jiang L AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Fei, Haiyi AU - Fei H AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Jin, Xiaoying AU - Jin X AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Liu, Xiu AU - Liu X AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Yang, Cuiyu AU - Yang C AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Li, Chao AU - Li C AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Chen, Jianmin AU - Chen J AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Yang, Anran AU - Yang A AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. FAU - Zhu, Jiajuan AU - Zhu J AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Medical, Jiaxing University Affiliated Women and Children Hospital, 314051, Jiaxing, China. FAU - Wang, Huihong AU - Wang H AD - Department of Obstetrics and Gynecology, Hangzhou Women's Hospital, 310008, Hangzhou, China. FAU - Fei, Xiaoyang AU - Fei X AD - Department of Obstetrics and Gynecology, Hangzhou Women's Hospital, 310008, Hangzhou, China. FAU - Zhang, Songying AU - Zhang S AD - Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China. AD - Department of Obstetrics and Gynecology, Key Laboratory of Reproductive Dysfunction, Management of Zhejiang Province, 310016, Hangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211022 PL - Australia TA - Int J Biol Sci JT - International journal of biological sciences JID - 101235568 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cell Line MH - Decidua/*cytology MH - Extracellular Vesicles/*metabolism MH - Female MH - Histocompatibility Antigens Class I/genetics/*metabolism MH - Humans MH - Interferon-gamma/genetics/metabolism MH - Killer Cells, Natural/*physiology MH - Mice MH - Mice, Nude MH - Placenta/cytology MH - Pregnancy MH - Tissue Culture Techniques MH - Trophoblasts/*physiology MH - Vascular Endothelial Growth Factor A/genetics/metabolism MH - HLA-E Antigens PMC - PMC8579460 OTO - NOTNLM OT - Extracellular Vesicles OT - HLA-E OT - decidual NK Cells OT - pregnancy OT - secretion COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2021/11/23 06:00 MHDA- 2021/12/21 06:00 PMCR- 2021/01/01 CRDT- 2021/11/22 06:37 PHST- 2021/06/01 00:00 [received] PHST- 2021/09/24 00:00 [accepted] PHST- 2021/11/22 06:37 [entrez] PHST- 2021/11/23 06:00 [pubmed] PHST- 2021/12/21 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - ijbsv17p4377 [pii] AID - 10.7150/ijbs.63390 [doi] PST - epublish SO - Int J Biol Sci. 2021 Oct 22;17(15):4377-4395. doi: 10.7150/ijbs.63390. eCollection 2021.