No abstract

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.

Preeclampsia (PE) is characterized by maternal hypertension, proteinuria, oedema and, in 30% of cases, by intrauterine growth retardation. Causes are still unknown; however, epidemiological and clinical studies have suggested alterations in maternal calcium metabolism. We suggested that in PE, calcium transport by the syncytiotrophoblast (ST) is disturbed. From total placental tissues, we studied the expression of: calcium channels (TRPV5, TRPV6 [transient receptor potential vanilloid]), calcium binding proteins (CaBP-9K, CaBP-28K), plasma membrane calcium ATPase (PMCA)1,2,3,4 pumps, ATP synthase, genes implicated in Ca2+ release [inositol-1,4,5-triphosphate receptor (IP3R)1,2,3; Ryanodine receptor (RyR)1,2,3] and replenishment (SERCA1,2,3 [sarcoendoplasmic reticulum Ca2+ ATPases]) from endoplasmic reticulum, channels implicated in mitochondrial Ca2+ accumulation (VDAC1,2,3 [voltage-dependent anion channels]) and a marker of oxidative stress (hOGG1 [Human 8-oxoguanine-DNA glycosylase 1]), as well as the influence of these variations on calcium transport in primary ST cultures. The mRNA and protein levels were thereby examined by real-time PCR and Western blot analysis, respectively, in two different groups of pregnant women with similar gestational age: a normal group (n= 16) and a PE group (n= 8), diagnosed by a clinician. Our study showed a significant decrease in calcium transport by the ST cultured from preeclamptic placentas. We found a significant (P < 0.05) decrease in mRNA levels of TRPV5, TRPV6, CaBP-9K, CaBP-28K, PMCA1, PMCA4, ATP synthase, IP3R1, IP3R2, RyR1, RyR2 and RyR3 in PE group compared to normal one. We also noted a significant decrease in protein levels of TRPV5, TRPV6, CaBP-9K, CaBP-28K and PMCA1/4 in PE group. In contrast, SERCA1, SERCA2, SERCA3, VDAC3 and hOGG1 mRNA expressions were significantly increased in PE placentas. Calcium homeostasis and transport through placenta is compromised in preeclamptic pregnancies and it appears to be affected by a lack of ATP and an excess of oxidative stress.