Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

Keqing Wang, Meng Cai, Wijdan Abu-Alkheir, Shakil Ahmad, Asif Ahmed

Research output: Contribution to journalMeeting abstract

Abstract

Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

LanguageEnglish
Article numberPP108
PagesS57-S58
Number of pages2
JournalNitric Oxide
Volume47
Issue numberSuppl.1
Early online date14 Apr 2015
DOIs
Publication statusPublished - 1 May 2015
Event3rd European Conference on the Biology of Hydrogen Sulfide - Athens, Greece
Duration: 3 May 20156 May 2015

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Cystathionine beta-Synthase
Fetal Development
Pre-Eclampsia
Cystathionine
Aminooxyacetic Acid
Lyases
Intercellular Signaling Peptides and Proteins
Placental Insufficiency
Placentation
Hydrogen Sulfide
Perinatal Mortality
Blood pressure
Trophoblasts
Pathology
Giant Cells
First Pregnancy Trimester
Glycogen
Birth Weight
Placenta
Nutrients

Bibliographical note

Abstract from the 3rd European Conference on the Biology of Hydrogen Sulfide (H2S 2015), 3–6 May 2015, Athens, Greece.

Cite this

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title = "Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction",
abstract = "Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.",
author = "Keqing Wang and Meng Cai and Wijdan Abu-Alkheir and Shakil Ahmad and Asif Ahmed",
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Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction. / Wang, Keqing; Cai, Meng; Abu-Alkheir, Wijdan; Ahmad, Shakil; Ahmed, Asif.

In: Nitric Oxide, Vol. 47, No. Suppl.1, PP108, 01.05.2015, p. S57-S58.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Dysregulation of placental cystathionine-β-synthase promotes fetal growth restriction

AU - Wang, Keqing

AU - Cai, Meng

AU - Abu-Alkheir, Wijdan

AU - Ahmad, Shakil

AU - Ahmed, Asif

N1 - Abstract from the 3rd European Conference on the Biology of Hydrogen Sulfide (H2S 2015), 3–6 May 2015, Athens, Greece.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

AB - Fetal growth restriction (FGR) is characterized by the birth weight and body mass below the tenth percentile for gestational age. FGR is a major cause of perinatal morbidity and mortality and babies born with FGR are prone to develop cardiovascular diseases later in life. The underlying pathology of FGR is inadequate placental transfer of nutrients from mother to fetus, which can be caused by placental insufficiency. Hydrogen sulfide (H2S), a gaseous messenger is produced endogenously by cystathionine-lyase (Cth), cystathionine-β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), which are present in human placenta. Recently, we demonstrated that the dysregulation of H2S/Cth pathway is associated with preeclampsia and blockade of CSE activity induces preeclampsia-like condition in pregnant mice. We hypothesized that defect in H2S pathways promote FGR and H2S donor restores fetal growth in mice where CBS or CSE activity has been compromised. Western blotting and qPCR revealed that placental CBS expressions were significantly reduced in women with FGR. ELISA analysis showed reduced placental growth factor production (PlGF) from first trimester (8–12 weeks gestation) human placental explants following inhibition of CBS activity by aminooxyacetic acid (AOA). Administration of AOA to pregnant mice had no effects on blood pressure, but caused fetal growth restriction. This was associated with reduced PlGF production. Histological analysis revealed a reduction in the placental junction zone, within which trophoblast giant cells and glycogen cells were less prominent in CBS inhibitor treated mice. These results imply that placental CBS is required for placental development and that dysregulation of CBS activity may contribute to the pathogenesis of FGR but not preeclampsia.

U2 - 10.1016/j.niox.2015.02.138

DO - 10.1016/j.niox.2015.02.138

M3 - Meeting abstract

VL - 47

SP - S57-S58

JO - Nitric Oxide

T2 - Nitric Oxide

JF - Nitric Oxide

SN - 1089-8603

IS - Suppl.1

M1 - PP108

ER -