Human endogenous retroviruses (HERVs) represent up to 8% of the human genome and express several of its genes in the placenta. Studies have demonstrated that HERV envelope proteins syncytins 1 and 2 play a crucial role in trophoblast fusion and placenta development. Here, we compared the levels of placental expression of syncytins with the severity of preeclampsia (PE) symptoms. Confocal microscopy experiments indicated a pronounced deficiency in cellular fusion in trophoblast cells from patients with PE when compared to controls. As determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot analyses, syncytin mRNA and protein levels were decreased in PE placentas versus controls. Interestingly, syncytin 2 levels were more importantly impaired than syncytin 1. Our results further highlighted the existence of a correlation between the extent of the decrease in the expression levels of both fusogenic proteins and the degree of severity of PE symptoms. These HERV proteins could thereby be used as potential markers for the early diagnosis of PE.
LöwerRLöwerJKurthR. The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc Natl Acad Sci U S A. 1996;93(11):5177–5184.
2.
LarssonEAnderssonG. Beneficial role of human endogenous retroviruses: facts and hypotheses. Scand J Immunol. 1998;48(4):329–338.
3.
MiSLeeXLiX. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature. 2000;403(6771):785–789.
4.
BlaiseSde ParsevalNBenitLHeidmannT. Genomewide screening for fusogenic .human endogenous retrovirus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci U S A. 2003;100(22):13013–13018.
5.
BlaiseSde ParsevalNHeidmannT. Functional characterization of two newly identified Human Endogenous Retrovirus coding envelope genes. Retrovirology. 2005;2:19.
6.
FrendoJLOlivierDCheynetV. Direct involvement of HERV-W Env glycoprotein in human trophoblast cell fusion and differentiation. Mol Cell Biol. 2003;23(10):3566–3574.
7.
BlondJ-LBesèmeFDuretL. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J Virol. 1999;73(2):1175–1185.
8.
MalassineABlaiseSHandschuhK. Expression of the fusogenic HERV-FRD Env glycoprotein (syncytin 2) in human placenta is restricted to villous cytotrophoblastic cells. Placenta. 2006;28(2-3):185–191.
9.
ChenCPChenLFYangSR. Functional characterization of the human placental fusogenic membrane protein syncytin 2. Biol Reprod. 2008;79(5):815–823.
10.
KeithJCJr. Pijnenborg R, Van Assche FA. Placental syncytin expression in normal and preeclamptic pregnancies. Am J Obstet Gynecol. 2002;187(4):1122–1123.
11.
LangbeinMStrickRStrisselPL. Impaired cytotrophoblast cell-cell fusion is associated with reduced Syncytin and increased apoptosis in patients with placental dysfunction. Mol Reprod Dev. 2008;75(1):175–183.
12.
KnerrIBeinderERascherW. Syncytin, a novel human endogenous retroviral gene in human placenta: evidence for its dysregulation in preeclampsia and HELLP syndrome. Am J Obstet Gynecol. 2002;186(2):210–213.
13.
LeeXKeithJCJr. Stumm N, et al. Downregulation of placental syncytin expression and abnormal protein localization in pre-eclampsia. Placenta. 2001;22(10):808–812.
14.
ChenCPWangKGChenCYYuCChuangHCChenH. Altered placental syncytin and its receptor ASCT2 expression in placental development and pre-eclampsia. Bjog. 2006;113(2):152–158.
15.
AcienPLloretGLloretM. Perinatal morbidity and mortality in pregnancy hypertensive disorders: prognostic value of the clinical and laboratory findings. Int J Gynaecol Obstet. 1990;32(3):229–235.
16.
WilsonMLGoodwinTMPanVLInglesSA. Molecular epidemiology of preeclampsia. Obstet Gynecol Surv. 2003;58(1):39–66.
17.
VargasAMoreauJLe BellegoFLafondJBarbeauB. Induction of trophoblast cell fusion by a protein tyrosine phosphatase inhibitor. Placenta. 2008;29(2):170–174.
18.
MayhewTM. Taking tissue samples from the placenta: an illustration of principles and strategies. Placenta. 2008;29(1):1–14.
19.
VargasAMoreauJLandryS. Syncytin-2 plays an important role in the fusion of human trophoblast cells. J Mol Biol. 2009;392(2):301–318.
20.
KlimanHJNestlerJESermasiESangerJMStraussJF3rd. Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology. 1986;118(4):1567–1582.
21.
GenbacevOJoslinRDamskyC. HPolliottiB. MFisherS. J. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occurs in preeclampsia. J Clin Invest. 1996;97(2):540–550.
22.
RedlineRWPattersonP. Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum Pathol. 1995;26(6):594–600.
23.
KudoYBoydCASargentILRedmanCW. Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. Biochim Biophys Acta. 2003;1638(1):63–71.
24.
WichCKauslerSDotschJRascherWKnerrI. Syncytin-1 and glial cells missing a: hypoxia-induced deregulated gene expression along with disordered cell fusion in primary term human trophoblasts. Gynecol. Obstet. Invest. 2009;68(1):9–18.
25.
KudakaWOdaTJinnoYYoshimiNAokiY. Cellular localization of placenta-specific human endogenous retrovirus (HERV) transcripts and their possible implication in pregnancy-induced hypertension. Placenta. 2008;29(3):282–289.
