Factors released from the human placentae, including extracellular vesicles, reduce the migration of endometriotic cells: A potential therapeutic for endometriosis.

Abstract

Endometriosis is characterised by the growth of abnormal endometrial tissue outside the uterus and chronic inflammation. Increasing evidence suggests that placenta extracellular vesicles (EVs) inhibit the growth and migration of ovarian and cervical cancer cells. This study investigated whether placental EVs have similar inhibitory effects on endometriotic cells. Human placental tissues were collected from the first trimester and cultured. The conditioned media were collected, and placental EVs were harvested. Endometriotic cell line 12Z cells were cultured with placental explant-conditioned media or placental EVs for 24 and 48 h. Cell proliferation, viability, migration, and invasion were then measured. The C19MC miRNAs were measured in 12Z cells after treatment. The proliferation and viability of 12Z cells were significantly reduced at 24 or 48 h after treatment with conditioned media compared with controls. Extracellular vesicles isolated from conditioned media also reduced proliferation and viability in 12Z cells, and this finding was confirmed by the transfection of miRNA mimics. Additionally, the migration and invasion of 12Z cells were significantly reduced after treatment. The levels of four C19MC miRNAs increased significantly in 12Z cells that had been treated with conditioned medium. This study demonstrates that factors released from the human placenta significantly inhibit endometriotic cell proliferation, migration, and inflammation. Placental EVs may contribute to these effects. These effects appear to be mediated, at least in part, by C19MC miRNAs. Our findings suggest that factors released from the human placentae, including extracellular vesicles, may be a novel therapeutic approach for managing endometriosis.