King's College London

Research portal

NPFF increases fusogenic proteins syncytin 1 and syncytin 2 via GCM1 in first trimester primary human cytotrophoblast cells

Research output: Contribution to journalArticlepeer-review

Hua Zhu, Bo Peng, Christian Klausen, Yuyin Yi, Yan Li, Siyuan Xiong, Peter von Dadelszen, Peter C.K. Leung

Original languageEnglish
Pages (from-to)9419-9432
Number of pages14
JournalFaseb Journal
Issue number7
Accepted/In press1 Jan 2020
Published1 Jul 2020

King's Authors


Neuropeptide FF (NPFF) is well-known for its roles in the central nervous system. Despite studies demonstrating that NPFF receptor 2 (NPFFR2) mRNA is highest in placenta, nothing is known about NPFF-NPFFR2 functions in placental development. Here, we investigated the effects of NPFF-NPFFR2 on expression of syncytial [human chorionic gonadotropin (hCG) β] and fusogenic [syncytin 1, syncytin 2, and glial cells missing 1 (GCM1)] genes in first trimester primary human cytotrophoblast cells. By analyzing two publicly available microarray data sets, we found that NPFF is consistently expressed throughout gestation whereas NPFFR2 increases in first trimester and is elevated in placenta samples from women with preeclampsia. Immunohistochemistry showed that NPFFR2, syncytin 1/2, and GCM1 each displayed unique patterns of expression among different trophoblast populations in first trimester placenta. Treatment of primary human cytotrophoblast cells with NPFF increased the mRNA and protein levels of hCG β, syncytin 1, syncytin 2, and GCM1; and knockdown of NPFFR2 abolished these effects. Interestingly, GCM1 mediated NPFF-induced upregulation of syncytin 1 and syncytin 2, but not hCG β, in primary human cytotrophoblasts. Our results demonstrate that NPFF acts via NPFFR2 to enhance production of hCG β and promote GCM1-dependent expression of syncytin 1 and 2 in human cytotrophoblasts.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454