Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction

Akturk, Aysi˙ma; Önal, Esra; Atalay, Yıldız; Yürekli, Muhittin; Erbas, Deni ̇z; Okumuş, Nurullah; Türkyılmaz, Canan; Unal, Suna; Ergenekon, Ebru; Koç, Esi˙N; Himmetoglu, Ö.

doi:10.1080/14767050701412263

Cited by 12 publications

(6 citation statements)

References 26 publications

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“…34 Alterations in ADM levels have also been associated with fetal growth in studies in human populations. [35][36][37][38] Our finding of a genetic variant in ADM associated with birth weight provides further evidence for the importance of maternal ADM in fetal growth.…”

Section: Discussionsupporting

confidence: 56%

Adrenomedullin Signaling Pathway Polymorphisms and Adverse Pregnancy Outcomes

et al. 2013

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Objective Reduced maternal plasma levels of the peptide vasodilator adrenomedullin have been associated with adverse pregnancy outcomes. We measured the extent to which genetic polymorphisms in the adrenomedullin signaling pathway are associated with birth weight, glycemic regulation, and preeclampsia risk. Study Design We genotyped 1353 women in the Pregnancy, Infection, and Nutrition Postpartum Study for 37 ancestry-informative markers and for single-nucleotide polymorphisms (SNPs) in adrenomedullin (ADM), complement factor H variant (CFH), and calcitonin receptor-like receptor (CALCRL). We used linear and logistic regression to model the association between genotype and birth weight, glucose loading test (GLT) results, preeclampsia, and gestational diabetes (GDM). All models were adjusted for pregravid BMI, maternal age, and probability of Yoruban ancestry. P values of <0.05 were considered statistically significant. Results Among Caucasian women, ADM rs57153895, a proxy for rs11042725, was associated with reduced birth weight z-score. Among African-American women, ADM rs57153895 was associated with increased birth weight z-score. Two CALCRL variants were associated with GDM risk. CFH rs1061170 was associated with higher GLT results and increased preeclampsia risk. Conclusion Consistent with studies of plasma adrenomedullin and adverse pregnancy outcomes, we found associations between variants in the adrenomedullin signaling pathway and birth weight, glycemic regulation, and preeclampsia.

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Section: Discussionsupporting

confidence: 56%

Adrenomedullin Signaling Pathway Polymorphisms and Adverse Pregnancy Outcomes

et al. 2013

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“…2004; Akturk et al . 2007; Nanetti et al . 2008); even fewer reports have examined placental tissue NOx concentrations in complicated pregnancies including pre‐eclampsia (Myatt et al .…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide metabolism in the human placenta during aberrant maternal inflammation

Mukosera

Clark

Ngo

et al. 2020

The Journal of Physiology

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Key points Nitric oxide (NO) is a gasotransmitter with important physiological and pathophysiological roles in pregnancy. There is limited information available about the sources and metabolism of NO and its bioactive metabolites (NOx) in both normal and complicated pregnancies. The present study characterized and quantified endogenous NOx in human and mouse placenta following determination of the stability of exogenous NOx in placental homogenates. NOx have differential stability in placental homogenates. NO and iron nitrosyl species (FeNOs), are relatively unstable in placental homogenates from normal placentas. Exogenous NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. FeNOs were also detected endogenously in mouse and human placenta. NOx levels in placental villous tissue are increased in fetal growth restriction vs. placentas from women with normal pregnancies, particularly in fetal growth restriction associated with pre‐eclampsia. Villitis was not associated, however, with an increase in NOx levels in either normotensive or pre‐eclamptic placentas. The results call for further investigation of FeNOs in normal and complicated pregnancies. Abstract Nitric oxide (NO) is a gasotransmitter with important roles in pregnancy under both physiological and pathophysiological conditions. Although products of NO metabolism (NOx) also have significant bioactivity, little is known about the role of NO and NOx under conditions of aberrant placental inflammation during pregnancy. An ozone‐based chemiluminescence approach was used to investigate the stability and metabolic fate of NOx in human placental homogenates from uncomplicated pregnancies in healthy mothers compared to that in placental tissue from normotensive and pre‐eclamptic pregnancies complicated with fetal growth restriction (FGR) with and without villitis of unknown aetiology. We hypothesized that placental NOx would be increased in FGR vs. normal tissue, and be further increased in villitis vs. non‐villitis placentas. Findings indicate that nitrate, nitrite and nitrosothiols, but not NO or iron nitrosyl species (FeNOs), are relatively stable in placental homogenates from normal placentas, and that NO, nitrite and nitrosothiols react with placental homogenates to form iron nitrosyl complexes. Furthermore, NOx levels in placental villous tissue are increased in FGR vs. placentas from women with normal pregnancies, particularly in FGR associated with pre‐eclampsia. However, in contrast to our hypothesis, villitis was not associated with an increase in NOx levels in either normotensive or pre‐eclamptic placentas. Our results also strongly support the involvement of FeNOs in both mouse and human placenta, and call for their further study as a critical mechanistic link between pre‐eclampsia and fetal growth restriction.

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“…al. showed no difference in AM concentrations between small for gestational age and appropriate for gestational age infants [51–52]. Based on animal studies, it is likely that altered AM levels may contribute to either the development of IUGR or the resulting adaptive compensation to other primary causes of IUGR.…”

Section: Adrenomedullin In Pregnancy Complicationsmentioning

confidence: 99%

Adrenomedullin and pregnancy: perspectives from animal models to humans

Lenhart¹,

Caron²

2012

Trends in Endocrinology & Metabolism

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A healthy pregnancy requires strict coordination of genetic, physiologic, and environmental factors. The relatively common incidence of infertility and pregnancy complications has resulted in increased interest in understanding the mechanisms that underlie normal versus abnormal pregnancy. The peptide hormone adrenomedullin has recently been the focus of some exciting breakthroughs in the pregnancy field. Supported by mechanistic studies in genetic animal models, there continues to be a growing body of evidence demonstrating the importance of adrenomedullin protein levels in a variety of human pregnancy complications. With more extensive mechanistic studies and improved consistency in clinical measurements of adrenomedullin, there is great potential for the development of adrenomedullin as a clinically-relevant biomarker in pregnancy and pregnancy complications.

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Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction

Abstract: We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.

Cited by 12 publications

References 26 publications

Adrenomedullin Signaling Pathway Polymorphisms and Adverse Pregnancy Outcomes

Adrenomedullin Signaling Pathway Polymorphisms and Adverse Pregnancy Outcomes

Nitric oxide metabolism in the human placenta during aberrant maternal inflammation

Adrenomedullin and pregnancy: perspectives from animal models to humans

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