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Decreased B7-H3 promotes unexplained recurrent miscarriage via RhoA/ROCK2 signaling pathway and regulates the secretion of decidual NK cells†.
- Source :
-
Biology of reproduction [Biol Reprod] 2023 Mar 13; Vol. 108 (3), pp. 504-518. - Publication Year :
- 2023
-
Abstract
- The cause for at least 50% of recurrent miscarriages is unclear, which is defined as unexplained recurrent miscarriages. The B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in unexplained recurrent miscarriages. We found reduced levels of B7-H3 in the villus tissue of unexplained recurrent miscarriage patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts. Further, the HTR-8/SVneo and JEG-3 cells were selected to explore the role of B7-H3 in proliferation, apoptosis, tube formation, migration, and invasion. We found that B7-H3 regulated trophoblast migration and invasion via RhoA/ROCK2 signaling pathway. Inflammatory cytokines were detected through enzyme-linked immunosorbent assay after co-culturing with decidual natural killer cells and B7-H3-knockout JEG-3. Results showed that B7-H3 inhibited IL-8 and IP-10 secretion from the decidual natural killer cells. In a CBA/J × DBA/2 abortion-prone mice model, treatment with B7-H3-Fc protein successfully reduced the rate of embryo resorption. In conclusion, our results revealed a possible mechanism by which decreased B7-H3 on trophoblasts of unexplained recurrent miscarriages inhibited trophoblast migration and invasion and increased IL-8 and IP-10 secretion from the decidual natural killer cells. Furthermore, B7-H3 may be a promising new therapeutic target in unexplained recurrent miscarriage patients.<br /> (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Animals
Female
Humans
Mice
Pregnancy
Cell Line, Tumor
Chemokine CXCL10 metabolism
Decidua metabolism
Killer Cells, Natural metabolism
Mice, Inbred CBA
Mice, Inbred DBA
rho-Associated Kinases metabolism
rhoA GTP-Binding Protein metabolism
Signal Transduction
Trophoblasts metabolism
Abortion, Habitual metabolism
Interleukin-8 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-7268
- Volume :
- 108
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biology of reproduction
- Publication Type :
- Academic Journal
- Accession number :
- 36504380
- Full Text :
- https://doi.org/10.1093/biolre/ioac220