title: Alteration of calcium homeostasis in primary preeclamptic syncytiotrophoblasts: effect on calcium exchange in placenta.
abstract: 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 Ca(2+) release [inositol-1,4,5-triphosphate receptor (IP3R)1,2,3; Ryanodine receptor (RyR)1,2,3] and replenishment (SERCA1,2,3 [sarcoendoplasmic reticulum Ca(2+) ATPases]) from endoplasmic reticulum, channels implicated in mitochondrial Ca(2+) 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.
authors.affiliation: Biomed Research Center, Department of Biological Sciences, University of Quebec at Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Haché
authors.forename: L
authors.initials: L
authors.lastname: Takser
authors.forename: F
authors.initials: F
authors.lastname: LeBellego
authors.forename: H
authors.initials: H
authors.lastname: Weiler
authors.forename: L
authors.initials: L
authors.lastname: Leduc
authors.forename: J C
authors.initials: JC
authors.lastname: Forest
authors.forename: Y
authors.initials: Y
authors.lastname: Giguère
authors.forename: A
authors.initials: A
authors.lastname: Masse
authors.forename: B
authors.initials: B
authors.lastname: Barbeau
authors.forename: J
authors.initials: J
authors.lastname: Lafond
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006706:Homeostasis; D006801:Humans; D017136:Ion Transport; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C492239:TRPV5 protein, human; C422827:TRPV6 protein, human; D050994:Voltage-Dependent Anion Channels; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D053499:Plasma Membrane Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium