Monoamine Oxidase Expression and Activity in Human Placentae from Pre-eclamptic and Normotensive Pregnancies

doi:10.1053/plac.2001.0770

Placenta

Volume 23, Issues 2–3, February 2002, Pages 163-171

https://doi.org/10.1053/plac.2001.0770 Get rights and content

Abstract

A feature of pre-eclampsia is that circulating levels of maternal serotonin (5-hydroxytryptamine) are elevated and placental monoamine oxidase-A (MAO-A) activity, the major factor in the regulation of serotonin levels in pregnancy, is reduced. It is not known whether this is due to a reduced MAO-A protein content or a reduced catalytic turnover of the serotonin by MAO-A; this question has been addressed in the present work. Term placentae from normotensive and pre-eclamptic women were analysed for MAO-A specific mRNA expression (by semi-quantitative RT-PCR), MAO-A protein (by immunohistochemistry and quantitative ELISA, using a MAO-A specific monoclonal antibody), together with MAO activity (using [³H] labelled 5-hydroxytryptamine as substrate). Immunohistochemical analysis of placentae from both normotensive and pre-eclamptic women demonstrated that MAO-A protein is located in the cytoplasm of the placental syncytiotrophoblast layer, consistent with a mitochondrial location; no MAO-A protein was found in the nucleus. No MAO-B protein was detected in this placental layer, despite the presence of MAO-B mRNA. The results indicate that both total protein/g fresh weight and MAO-A protein/g fresh weight were approximately 40 per cent lower in pre-eclamptic than in normotensive placentae, but that there was no statistical difference in the expression of MAO-A mRNA in relation to GAPDH or actin mRNA or in MAO-A protein/mg total protein. However, MAO-A activity/g fresh weight was significantly reduced in pre-eclamptic placentae, in agreement with previous findings. This was found to be due to a 60 per cent reduction (P< 0.05) in the catalytic turnover (activity/molecule) of the enzyme. This study has therefore clearly shown that the expression of placental MAO-A specific mRNA and MAO-A protein are not specifically affected in pre-eclampsia, but that the catalytic efficiency of the expressed MAO-A enzyme in pre-eclamptic placentae is greatly reduced.

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Certain monoamine oxidase (MAO) inhibitors exhibit beneficial effects, such as reducing adiposity and metabolic disorders; however, their effects on hepatic lipid metabolism have not been revealed. This study aimed to investigate the effects of a selective MAO-B inhibitor, selegiline, on dyslipidemia and hepatic steatosis in mice induced by a high-fat diet (HFD). Administration of selegiline (0.6 mg/kg body weight) by intraperitoneal injection was found to reduce HFD-induced body weight gain and increases in liver and adiposity coefficients, blood lipids and fatty acid levels. Furthermore, selegiline dramatically reduced the total triglyceride (TG) and cholesterol (TC) levels and lipid accumulation in the livers of HFD-fed mice and palmitic acid (PA)-treated AML-12 hepatocytes. In vivo and in vitro results indicated that selegiline protects against HFD- and PA-induced hepatic inflammation by reducing the expression of proinflammatory cytokines, namely IL-6, TNF‐α, IL‐1β, and IL‐1α. Additionally, selegiline exhibited antioxidative effects on HFD and PA exposure in mouse liver and AML-12 cells by decreasing the levels of reactive oxygen species (ROS) and malonaldehyde (MDA) and increasing superoxide dismutase (SOD) activity. Further study showed that selegiline administration mitigated the expression of Srebf-1, Fasn, and Acaca and downregulated the expression of Cpt-1 and Pparα in HFD-fed mouse livers and PA-treated AML-12 cells. In conclusion, our findings suggest that selegiline exerts protective effects against HFD-induced dyslipidemia and hepatic steatosis, which may be related to an improved inflammatory response, oxidative stress, and hepatic lipid metabolism.
Serotonin-estrogen interactions: What can we learn from pregnancy?
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Citation Excerpt :
It would rather result from platelet activation following endothelial damage [377]. Pre-eclampsia placentas have lower 5-HT metabolism and MAOA expression, while SERT activity and expression are not affected [378–380] and resulting placental 5-HT concentrations are increased [380]. In pre-eclampsia, 5-HT7R expression, a G protein-coupled receptor (Gs) involved notably in anxiety, mood and vasoconstriction, is increased about 8 times in the placenta [321,376], but the significance of this important increase remains to be characterized.
We have reviewed the scientific literature related to four diseases in which to serotonin (5-HT) is involved in the etiology, herein named 5-HT-linked diseases, and whose prevalence is influenced by estrogenic status: depression, migraine, irritable bowel syndrome and eating disorders. These diseases all have in common a sex-dimorphic prevalence, with women more frequently affected than men. The co-occurrence between these 5-HT-linked diseases suggests that they have common physiopathological mechanisms. In most 5-HT-linked diseases (except for anorexia nervosa and irritable bowel syndrome), a decrease in the serotonergic tone is observed and estrogens are thought to contribute to the improvement of symptoms by stimulating the serotonergic system. Human pregnancy is characterized by a unique 5-HT and estrogen synthesis by the placenta. Pregnancy-specific disorders, such as hyperemesis gravidarum, gestational diabetes mellitus and pre-eclampsia, are associated with a hyperserotonergic state and decreased estrogen levels. Fetal programming of 5-HT-linked diseases is a complex phenomenon that involves notably fetal-sex differences, which suggest the implication of sex steroids. From a mechanistic point of view, we hypothesize that estrogens regulate the serotonergic system, resulting in a protective effect against 5-HT-linked diseases, but that, in turn, 5-HT affects estrogen synthesis in an attempt to retrieve homeostasis. These two processes (5-HT and estrogen biosynthesis) are crucial for successful pregnancy outcomes, and thus, a disruption of this 5-HT-estrogen relationship may explain pregnancy-specific pathologies or pregnancy complications associated with 5-HT-linked diseases.
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Citation Excerpt :
Monoamine oxidase is involved in the oxidative deamination of neurotransmitters such as serotonin, and this enzyme has also been investigated as a target for prodrug activation [120]. Reduced activity of monoamine oxidase A in placentas from preeclamptic pregnancies may be responsible for increases in serotonin levels and blood pressure [121]. Glucuronide conjugation is conducted by uridine 5′-diphosphate glucuronosyltransferase enzymes, or UGTs.
The placenta serves as the interface between the maternal and fetal circulations and regulates the transfer of oxygen, nutrients, and waste products. When exogenous substances are present in the maternal bloodstream—whether from environmental contact, occupational exposure, medication, or drug abuse—the extent to which this exposure affects the fetus is determined by transport and biotransformation processes in the placental barrier. Advances in drug delivery strategies are expected to improve the treatment of maternal and fetal diseases encountered during pregnancy.
Placenta and Placental Transport Function
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For all eutherian mammals, the placenta forms the interface between the fetus and the mother, providing all functions that are essential for fetal survival, growth, and development, including gas exchange, nutrient transport, removal of waste products, production of essential hormones, and establishment of fetal immunological defense. Although all placentas fulfill these functions, marked differences exist among different organisms with respect to placental shape, vascularity, blood flow, and tissue interface, resulting in marked structural and functional diversity. The basic unit of the human placenta, the villus, contains fetal blood vessels and is surfaced by the trophoblast, which is directly bathed in the maternal blood. The trophoblast regulates the transport of gases, water, electrolytes, glucose, amino acids, lipids, vitamins, micronutrients, and immunoglobulins, and controls acid–base balance and the transfer of drugs and xenobiotics. When resources are limited, the placenta is uniquely positioned to integrate a number of maternal and fetal signals in order to balance fetal demands with maternal resources, negotiating the growth and homeostatic needs of the two organisms.
Maternal prenatal symptoms of depression and down regulation of placental monoamine oxidase A expression
2013, Journal of Psychosomatic Research
Citation Excerpt :
The current investigation is the first to examine the association between maternal mood and placental MAO A expression. However pre-eclampsia, a condition in which maternal 5-HT is raised, has been associated with a 40% reduction in placental MAO A activity [31]. No relationship was found in that study with MAO A expression, suggesting posttranslational modifications to the protein.
Maternal prenatal symptoms of depression and anxiety have been associated with altered neurodevelopmental outcomes in the child. These effects may be mediated in part by altered placental function, with increased fetal 5-hydroxytryptamine (5-HT) exposure being one possible mechanism. The current study aimed to determine whether maternal symptoms of depression or anxiety were associated with decreased placental expression of monoamine oxidase A (MAO A), the enzyme which metabolises 5-HT into 5-hydroxyindoleacetic acid. The localisation of MAO A in the placenta was also investigated.
Pregnant women were recruited one day prior to elective caesarean and assessed using psychometric tests for symptoms of depression (Edinburgh Depression Scale) and anxiety (Spielberger State/Trait Index). Villous trophoblast tissue was extracted from each placenta and used for subsequent gene expression analysis (N = 62). Localisation was studied using immunohistochemistry, with a specific polyclonal antibody.
Increasing symptoms of maternal depression were associated with a reduction in placental MAO A expression (r = − 0.339, p = 0.007, N = 62). There was a trend for a similar correlation with symptoms of maternal trait anxiety, but not with state anxiety. MAO A was localised to the syncytiotrophoblast, the tissue between maternal and fetal blood.
These findings support the hypothesis that maternal mood is associated with altered placental function. A reduction in placental MAO A expression is consistent with a subsequent increase in fetal exposure to 5-HT.

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^f1: To whom correspondence should be addressed at: Department of Life Sciences, The Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, UK.

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Regular ArticlesMonoamine Oxidase Expression and Activity in Human Placentae from Pre-eclamptic and Normotensive Pregnancies

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Monoamine Oxidase Expression and Activity in Human Placentae from Pre-eclamptic and Normotensive Pregnancies