The Role of Syncytin in Placental Angiogenesis and Fetal Growth.

Background: Syncytin, a retroviral envelope protein, is specifically expressed on trophoblast cells and mediates formation of the syncytiotrophoblast through fusogenic activity. Decreased expression of Syncytin was found in fetal growth restriction placentas. Results: By generating an inducible knockout of the syncytin-a gene in mice, we show a specific disruption of placental angiogenesis with abnormal formation of two syncytiotrophoblast layers. Consistent with the defects observed in vivo, conditioned medium collected from trophoblast cells, following Syncytin-1 knockdown, contains lower expression of vascular endothelial growth factor and placental growth factor, and higher levels of soluble fms-like protein kinase-1 in BeWo and HTR-8/SVneo cells which related with suppressed PI3K/Akt/mTOR pathway, and is reduced in ability to induce tube formation by HUVECs. Conclusion: Syncytin participates in angiogenesis during placental development was first identified both in vivo and in vitro. Here, we give a new sight on understanding syncytin and pathophysiology of placenta related disease such as fetal growth restriction.

Inducible knockout of syncytin-a leads to poor placental glucose transport in mice.

INTRODUCTION: Cell-cell fusion of cytotrophoblasts into the syncytiotrophoblast layer is a key process in placental development. Syncytin, an endogenous retroviral envelope protein, is expressed in placental trophoblasts and specifically mediates syncytiotrophoblast layer formation. Syncytin deficiency has been observed in fetal growth-restricted placentas. Abnormal fetal growth, especially fetal growth restriction, is associated with the decreased expression of glucose transporters. Here, we aimed to determine the role of syncytin in fetal growth restriction in placental glucose transport capacity. METHODS: To better explore the function of syncytin in fetal growth-restricted placenta, we generated an inducible knockout mouse model of syncytin-a gene. The expression levels of glucose transporters in BeWo cells were measured before and after HERV-W knockdown. RESULTS: Syncytin-A disruption was associated with significant abnormalities in placental and fetal development in mice. Syncytin-A destruction causes extensive abnormalities in the maternal-fetal exchange structures in the labyrinth, including an extremely reduced number and dramatically irregular distribution of fetal vessels. Moreover, glucose transporter 1, glucose transporters 3, and connexin 26 expression levels decreased after E14.5. Consistently, low glucose transporter 1, glucose transporter 3, and connexin 26 levels were observed in HERV-W-silenced BeWo cells. DISCUSSION: Syncytin-A is crucial for both syncytiotrophoblast layer development and morphogenesis, suggesting that syncytin-A disruption leads to fetal growth restriction associated with abnormalities in the maternal-fetal exchange barrier and decreased glucose transport.

DNAJC12 as a Mediator Between ESR1 and ERBB4 in Breast Carcinoma Cells.

Mutation of the DNAJC12 gene is typically associated with non-progressive Parkinsonism, but is also detectable in breast carcinoma where its contribution and mechanisms are unexplored. In breast carcinoma, ESR1 was positively correlated with DNAJC12 and ERBB4, and DNAJC12 was positively correlated with ERBB4. We used the GEO2R tool to compare differential gene expression of MCF-7 cells, following ESR1 knockdown (GEO database, E-GEOD-27473 array), and found decreased expression of DNAJC12 and ERBB4 in ESR1-silenced MCF-7 cells. The number of identical genes having correlativity with ESR1, DNAJC12, or ERBB4 was 12,165 (66.41%). These results suggest that ESR1 can promote the expression of DNAJC12 and ERBB4, and DNAJC12 can enhance the expression of ERBB4 in MCF-7 cells, implying that there may be a regulatory network among these three genes.