PMID- 35816776
OWN - NLM
STAT- MEDLINE
DCOM- 20220816
LR  - 20220901
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Linking)
VI  - 126
DP  - 2022 Aug
TI  - Beyond fusion: A novel role for ERVW-1 in trophoblast proliferation and type I 
      interferon receptor expression.
PG  - 150-159
LID - S0143-4004(22)00294-6 [pii]
LID - 10.1016/j.placenta.2022.06.012 [doi]
AB  - INTRODUCTION: Throughout human pregnancy there is a delicate balance between the 
      maintenance of a proliferative, trophoblast stem cell pool (TSC) and the 
      differentiation from TSC to placental cell sub-lineages like the 
      syncytiotrophoblast (STB). The STB is comprised of multinucleated cells that come 
      into direct contact with maternal blood and provides the first line of defense to 
      protect the fetus from maternal infections. The differentiation of TSC towards 
      STB is primarily driven by human endogenous retroviruses (HERV), specifically 
      Syncytin-1 (ERVW-1) and Syncytin-2 (ERVFRD-1). Beyond cell fusion, there is also 
      evidence to suggest they can regulate cell proliferation and an antiviral 
      response in other cell types. Therefore, we hypothesized that HERV can regulate 
      cell proliferation as well as an antiviral response in TSCs. METHOD: shRNA was 
      used to knockdown ERVW-1 in TSCs and revealed reduction in cell proliferation, 
      differentiation, and cell fusion. RT-qPCR and flow cytometry was used to measure 
      other HERV and the presence of Type I and Type II interferon receptors. RESULTS: 
      ERVW-1 knockdown (KD) TSCs had a significantly longer cell doubling time and 
      reduced expression of the proliferation marker Ki67. ERVW-1 KD cells also 
      demonstrated a marked deficiency in the ability to differentiate. Interestingly, 
      ERVFRD-1 was upregulated in both ERVW-1 KD TSC and STB cells compared to 
      controls. Finally, we found that the Type I interferon receptors, IFNAR1 and 
      IFNAR2 were significantly increased in ERVW-1 KD STB cells. DISCUSSION: These 
      findings uncover critical HERV functions in the trophoblasts and a novel role for 
      ERVW-1 during early human placental development.
CI  - Published by Elsevier Ltd.
FAU - C West, Rachel
AU  - C West R
AD  - Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA; Auburn 
      University, Department of Anatomy, Physiology, Pharmacology, Auburn, AL, 36849, 
      USA. Electronic address: rcw0043@auburn.edu.
FAU - Ezashi, Toshihiko
AU  - Ezashi T
AD  - Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA.
FAU - B Schoolcraft, William
AU  - B Schoolcraft W
AD  - Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA.
FAU - Yuan, Ye
AU  - Yuan Y
AD  - Colorado Center for Reproductive Medicine, Lone Tree, CO, 80124, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220705
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (Antiviral Agents)
RN  - 0 (Gene Products, env)
RN  - 0 (IFNAR1 protein, human)
RN  - 0 (Pregnancy Proteins)
RN  - 0 (syncytin)
RN  - 156986-95-7 (Receptor, Interferon alpha-beta)
SB  - IM
MH  - Antiviral Agents
MH  - Cell Proliferation
MH  - *Endogenous Retroviruses/genetics
MH  - Female
MH  - Gene Products, env
MH  - Humans
MH  - Placenta/metabolism
MH  - Pregnancy
MH  - Pregnancy Proteins
MH  - Receptor, Interferon alpha-beta/genetics/metabolism
MH  - *Trophoblasts/metabolism
OTO - NOTNLM
OT  - ERVFRD-1
OT  - ERVW-1
OT  - Placenta
OT  - Syncytiotrophoblast
OT  - Trophoblast stem cells
OT  - Type I interferon Receptors
EDAT- 2022/07/12 06:00
MHDA- 2022/08/17 06:00
CRDT- 2022/07/11 18:13
PHST- 2022/01/31 00:00 [received]
PHST- 2022/05/23 00:00 [revised]
PHST- 2022/06/26 00:00 [accepted]
PHST- 2022/07/12 06:00 [pubmed]
PHST- 2022/08/17 06:00 [medline]
PHST- 2022/07/11 18:13 [entrez]
AID - S0143-4004(22)00294-6 [pii]
AID - 10.1016/j.placenta.2022.06.012 [doi]
PST - ppublish
SO  - Placenta. 2022 Aug;126:150-159. doi: 10.1016/j.placenta.2022.06.012. Epub 2022 
      Jul 5.