Severe preeclampsia is associated with high inhibin A levels and normal leptin levels at 7 to 13 weeks into pregnancy

Salomon, Laurent; Benattar, C; Audibert, François; Fernandez, H.; Duyme, M.; Taieb, Julien; Frydman, René

doi:10.1016/s0002-9378(03)00902-5

Cited by 54 publications

(32 citation statements)

References 32 publications

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“…In PE serum, leptin was found to be increased after the onset of maternal symptoms [23] . More recent studies, however, did not find elevated serum leptin levels in the first [24] or second [25] trimester of subsequently pre-eclamptic pregnancies.…”

Section: Introductionmentioning

confidence: 77%

First Trimester Markers for Pre-Eclampsia: Placental vs<i>.</i> Non-Placental Protein Serum Levels

Zwahlen

Gerber

Bersinger

2006

Gynecol Obstet Invest

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Background/Aim: Parallel investigation, in a matched case-control study, of the association of different first-trimester markers with the risk of subsequent pre-eclampsia (PE). Method: The levels of different first trimester serum markers and fetal nuchal translucency thickness were compared between 52 cases of PE and 104 control women by non-parametric two-group comparisons and by calculating matched odds ratios. Results: In univariable analysis increased concentrations of inhibin A and activin A were associated with subsequent PE (p < 0.02). Multivariable conditional logistic regression models revealed an association between increased risk of PE and increased inhibin A and translucency thickness and respectively reduced pregnancy-associated plasma protein A (PAPP-A) and placental lactogen . However, these associations varied with the gestational age at sample collection. For blood samples taken in pregnancy weeks 12 and 13 only, increased levels of activin A, inhibin A and nuchal translucency thickness, and lower levels of placenta growth factor and PAPP-A were associated with an increased risk of PE. Conclusions: Members of the inhibin family and to some extent PAPP-A and placental growth factor are superior to other serum markers, and the predicitive value of these depends on the gestational age at blood sampling. The availability of a single, early pregnancy ‘miracle’ serum marker for PE risk assessment seems unlikely in the near future.

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Section: Introductionmentioning

confidence: 77%

First Trimester Markers for Pre-Eclampsia: Placental vs<i>.</i> Non-Placental Protein Serum Levels

Zwahlen

Gerber

Bersinger

2006

Gynecol Obstet Invest

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“…** Subfertility and its treatment (especially the use of donor eggs, sperm and/or gametes), after correction for multiple gestations. *** Decreased first trimester PAPP-A (pregnancy-associated plasma protein A) 65th centile [141], decreased first or second trimester PlGF (placental growth factor) [154][155][156], unexplained increased second trimester AFP (alphafetoprotein) [142][143][144][145][146][147], increased second trimester hCG [145][146][147][148], increased first or second trimester inhibin A [144,[149][150][151][152], increased second trimester activin. [153].…”

Section: Preventing Preeclampsia and Its Complicationsmentioning

confidence: 99%

RETIRED: Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy

Magee

Pels

Helewa

et al. 2008

Journal of Obstetrics and Gynaecology Canada

421

218

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“…In vivo, we previously observed decreased placental DNA methylation of 20% points at the INHBA promoter in preeclampsia, as well as a non-significant trend towards increased gene expression . Other studies have found INHBA mRNA to be significantly up-regulated in pre-eclampsia-associated placentae (Enquobahrie et al, 2008;Hoegh et al, 2010) and an elevation of inhibin A in maternal plasma of women with pre-eclampsia (Bersinger et al, 2003;Salomon et al, 2003). Thus, these in vitro and in vivo data point towards DNA methylation as a potential contributor to the elevated INHBA/inhibin A observed in pre-eclampsia.…”

Section: Discussionmentioning

confidence: 66%

Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down

Hogg

Robinson

Beristain

2014

MHR: Basic Science of Reproductive Medicine

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Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications, yet the transcriptional impact of such findings is not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylated in pre-eclampsia-associated placentae in vivo. We aimed to determine whether reduced DNA methylation at specific loci was associated with transcriptional changes at the corresponding gene, thus providing mechanistic underpinnings for previous clinical findings and to assess the degree of transcriptional response amongst our candidate genes. BeWo and JEG3 choriocarcinoma cells were exposed to 1 mM 5-Aza-2 ′ -deoxycytidine (5-Aza-CdR) or vehicle control for 48 h, and re-plated and cultured for a further 72 h in normal media before cells were harvested for RNA and DNA. Bisulphite pyrosequencing confirmed that DNA methylation was reduced by 30 -50% points at the selected loci studied in both cell lines. Gene activation, measured by qRT-PCR, was highly variable and transcript specific, indicating differential sensitivity to DNA methylation. Most notably, loss of DNA methylation at the leptin (LEP) promoter corresponded to a 200-fold and 40-fold increase in LEP expression in BeWo and JEG3 cells, respectively (P , 0.01). Transcripts of steroidogenic pathway enzymes CYP11A1 and HSD3B1 were up-regulated 40-fold in response to 5-Aza-CdR exposure in BeWo cells (P , 0.01). Other transcripts, including aromatase (CYP19), HSD11B2, inhibin (INHBA) and glucocorticoid receptor (NR3C1) were more moderately, although significantly, affected by loss of associated DNA methylation. These data present a mixed effect of DNA methylation changes at selected loci supporting cautionary interpretation of DNA methylation results in the absence of functional data.

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Severe preeclampsia is associated with high inhibin A levels and normal leptin levels at 7 to 13 weeks into pregnancy

Cited by 54 publications

References 32 publications

First Trimester Markers for Pre-Eclampsia: Placental vs<i>.</i> Non-Placental Protein Serum Levels

First Trimester Markers for Pre-Eclampsia: Placental vs<i>.</i> Non-Placental Protein Serum Levels

RETIRED: Diagnosis, Evaluation, and Management of the Hypertensive Disorders of Pregnancy

Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down

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