Dynamics of Base Excision Repair at the Maternal-Fetal Interface in Pregnancies Complicated by Preeclampsia

Serkalem Tadesse, Nicholas G. Norwitz, Seth Guller, Felice Arcuri, Paolo Toti, Errol R. Norwitz, Dawit Kidane

Research output: Contribution to journalArticle

Abstract

Preeclampsia (PE) (gestational proteinuric hypertension) is the leading cause of maternal and perinatal mortality worldwide. Although placental endothelial dysfunction and oxidative stress are known to contribute to PE, the exact pathological basis for this disorder remains unclear. Previously, we demonstrated that DNA damage at the maternal-fetal interface is more common in the placentas of women with PE than normotensive controls. In this study, we utilized an in vivo comparative study, including 20 preeclamptic women and 8 healthy control subjects, and an in vitro hypoxia/reperfusion model to mimic the effects of oxidative stress at the maternal-fetal interface. We tracked the spatial pattern of expression of 2 base excision repair proteins, 8-oxoguanine glycosylase (OGG1) and apurinic/apyrimidinic endonuclease-1 (APE1), at the maternal-fetal interface in response to oxidative stress. In vivo, we found a significant increase in OGG1 and APE1 concentrations in PE placental tissues as compared to normotensive controls (P <.0001). Further, our in vitro study revealed that OGG1 and APE1 expression is much greater in maternal cells (decidua) than in fetal cells (cytotrophoblasts) of placental tissue subjected to oxidative stress (P <.0001). Our results suggest that OGG1 and APE1 likely protect decidual cells from oxidative base damage.

Original languageEnglish (US)
Pages (from-to)856-864
Number of pages9
JournalReproductive Sciences
Volume24
Issue number6
DOIs
StatePublished - Jan 1 2017

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Pre-Eclampsia
DNA Repair
Endonucleases
Oxidative Stress
Mothers
Pregnancy
DNA-(Apurinic or Apyrimidinic Site) Lyase
Decidua
Pregnancy Induced Hypertension
Maternal Mortality
Perinatal Mortality
Trophoblasts
Placenta
DNA Damage
Reperfusion
Healthy Volunteers
Proteins
In Vitro Techniques

Keywords

  • OGG1 and APE1
  • base excision repair
  • preeclampsia

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Dynamics of Base Excision Repair at the Maternal-Fetal Interface in Pregnancies Complicated by Preeclampsia. / Tadesse, Serkalem; Norwitz, Nicholas G.; Guller, Seth; Arcuri, Felice; Toti, Paolo; Norwitz, Errol R.; Kidane, Dawit.

In: Reproductive Sciences, Vol. 24, No. 6, 01.01.2017, p. 856-864.

Research output: Contribution to journalArticle

Tadesse, Serkalem ; Norwitz, Nicholas G. ; Guller, Seth ; Arcuri, Felice ; Toti, Paolo ; Norwitz, Errol R. ; Kidane, Dawit. / Dynamics of Base Excision Repair at the Maternal-Fetal Interface in Pregnancies Complicated by Preeclampsia. In: Reproductive Sciences. 2017 ; Vol. 24, No. 6. pp. 856-864.
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