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Differential gene expression and limited epigenetic dysregulation at the materno-fetal interface in preeclampsia

journal contribution
posted on 2020-01-15, 00:00 authored by M N Leseva, A M Binder, A L Ponsonby, Peter VuillerminPeter Vuillermin, R Saffery, K B Michels
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com. Despite the many advances made in the diagnosis and management of preeclampsia, this syndrome remains a leading cause of maternal mortality and life-long morbidity, as well as adverse fetal outcomes. Successful prediction and therapeutic intervention require an improved understanding of the molecular mechanisms, which underlie preeclampsia pathophysiology. We have used an integrated approach to discover placental genetic and epigenetic markers of preeclampsia and validated our findings in an independent cohort of women. We observed the microRNA, MIR138, to be upregulated in singleton preeclamptic placentas; however, this appears to be a female infant sex-specific effect. We did not identify any significant differentially methylated positions (DMPs) in singleton pregnancies, indicating that DNA methylation changes in mild forms of the disease are likely limited. However, we identified infant sex-specific preeclampsia-associated differentially methylated regions among singletons. Disease-associated DMPs were more obvious in a limited sampling of twin pregnancies. Interestingly, 2 out of the 10 most significant changes in methylation over larger regions overlap between singletons and twins and correspond to NAPRT1 and ZNF417.

History

Journal

Human Molecular Genetics

Volume

29

Issue

2

Pagination

335 - 350

Publisher

Oxford Academic

Location

Oxford, Eng.

ISSN

0964-6906

eISSN

1460-2083

Language

eng

Publication classification

C1 Refereed article in a scholarly journal