Maternal Serum Melatonin Increases During Pregnancy and Falls Immediately After Delivery Implicating the Placenta as a Major Source of Melatonin

Melatonin is a neuroendocrine hormone which regulates circadian rhythm and is also an antioxidant. The role of melatonin in pregnancy is emerging. The enzymes needed for endogenous synthesis of melatonin have been identified in the placenta, although the contribution to circulating maternal melatonin in normal pregnancy is unclear. This work aimed to determine serum levels of melatonin and its major metabolite 6-hydroxymelatonin sulfate (6-OHMS) in normal pregnant women during each trimester of pregnancy, and immediately after delivery. Blood samples were obtained from a cohort of healthy pregnant women during each trimester of pregnancy (n = 26), from women scheduled for elective Cesarean section (CS) before and after delivery (n = 15), along with placental samples, and from healthy non-pregnant women as controls (n = 30). Melatonin and its major metabolite, 6-OHMS, were measured using enzyme immunoassay. Levels of serum melatonin were significantly higher during pregnancy than in non-pregnant women (P = 0.025) and increased throughout pregnancy (P < 0.0001). In women undergoing CS, serum melatonin decreased markedly 24 h after delivery (P = 0.0013). Similar results were seen for serum levels of 6-OHMS, and placental tissue 6-OHMS levels correlated with week of gestation at delivery (p = 0.018). In summary, maternal melatonin production is higher in pregnant than in non-pregnant women, increases significantly during pregnancy with highest levels in the third trimester, and decreases abruptly after delivery. These results suggest that the placenta is a major source of melatonin and supports a physiological role for melatonin in pregnancy.

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Enhancement of plasma corticotropin-releasing hormone in pregnancy-induced hypertension

Acta Endocrinologica ◽

10.1530/acta.0.1220711 ◽

1990 ◽

Vol 122 (6) ◽

pp. 711-714 ◽

Cited By ~ 20

Author(s):

W. Jeske ◽

P. Soszyński ◽

E. Lukaszewicz ◽

R. Dȩbski ◽

W. Latoszewska ◽

...

Keyword(s):

Pregnant Women ◽

Gestational Age ◽

Placental Tissue ◽

Normal Pregnancy ◽

Placental Lactogen ◽

Control Group ◽

Pregnancy Induced Hypertension ◽

Human Placental Lactogen ◽

Induced Hypertension ◽

In Pregnancy

Abstract. The role of a high CRH level in normal pregnancy remains unknown. Therefore we evaluated the concentrations of CRH and the related hormones in patients with pregnancy-induced hypertension. Fourteen women with pregnancy-induced hypertension, aged 20-39, at 30-39 gestational week, were investigated. The control group consisted of 20 healthy pregnant women matched according to gestational age. Plasma CRH, β-endorphin-like immunoreactivity, cortisol, and human placental lactogen were measured by radioimmunoassay, ACTH by an immunoradiometric method. It was found that in hypertensive patients the mean CRH concentration was significantly higher (4257±840 (sem) ng/l) than that in healthy pregnant women (1083±227 ng/l, p<0.001). The concentration of ACTH, however, was only slightly higher 65.0±6.0 vs 50.7±2.5 ng/l, p<0.025, whereas the differences in β-endorphin, cortisol and human placental lactogen were not significant. In both groups there was no correlation between the CRH level and those of the related hormones. In healthy pregnant women the CRH level closely correlated with gestational age (r=0.76, p<0.001), whereas in patients with hypertension no such correlation was present (r=0.29). We assume that the marked enhancement of plasma CRH in pregnancy-induced hypertension is probably caused by its decreased breakdown in ischemic placental tissue, but its increased synthesis in the placenta and its indirect counterregulatory hypotensive role must also be considered.

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Comparison of Maternal Serum Levels and Placental mRNA Levels of Dickkopf-1 in Preeclamptic and Normal Pregnant Women at Delivery

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-1557-1234 ◽

2021 ◽

Vol 81 (11) ◽

pp. 1247-1255

Author(s):

Mariz Kasoha ◽

Zoltan Takacs ◽

Lena Fackiner ◽

Christoph Gerlinger ◽

Panagiotis Sklavounos ◽

...

Keyword(s):

Pregnant Women ◽

Serum Levels ◽

Normal Pregnancy ◽

Maternal Serum ◽

Mrna Levels ◽

Mortality And Morbidity ◽

Significant Difference ◽

Fetal Complications ◽

Development Processes ◽

Dickkopf 1

Abstract Background Preeclampsia remains a major cause of perinatal and maternal mortality and morbidity worldwide. Wnt/β-catenin signaling is known to be critically involved in placenta development processes. Dickkopf-1 (DKK1) is a key regulator of this transduction pathway. The aim of this study is to compare maternal serum DKK1 levels and placental mRNA levels of DKK1 and β-catenin in preeclamptic and normal pregnant women at delivery. Methods The present study included 30 women with preeclampsia and 30 women with normal pregnancy. Maternal serum DKK1 levels were measured by ELISA. Placental mRNA levels of DKK1 and β-catenin were detected using RT-PCR. Results Decreased maternal serum DKK1 levels were associated with worse maternal and fetal complications including HELLP syndrome, determination of one or more pathological symptom and IUGR diagnosis. No significant difference in maternal serum DKK1 levels was reported between preeclamptic women and women with normal pregnancy. Placental mRNA DKK1 levels were lower in preeclamptic women compared with normal pregnant women. Placental mRNA β-catenin levels showed no significant difference between two groups. Conclusions Our findings reported the aberrant placental mRNA DKK1 levels in patients with preeclampsia. In addition, worse preeclampsia features were associated with decreased maternal serum DKK1 levels. Hence, aberrant Wnt/β-catenin signaling might present a plausible mechanism in preeclampsia pathogenicity. Dysregulated expression of DKK1 at gene level in the placenta but not at protein level in the maternal serum might confirm the notion that preeclampsia is a type of placenta-derived disease.

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The identification of irisin in human cerebrospinal fluid: influence of adiposity, metabolic markers, and gestational diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00308.2013 ◽

2014 ◽

Vol 306 (5) ◽

pp. E512-E518 ◽

Cited By ~ 78

Author(s):

Milan K. Piya ◽

Alison L. Harte ◽

Kavitha Sivakumar ◽

Gyanendra Tripathi ◽

Philip D. Voyias ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Gestational Diabetes ◽

Pregnant Women ◽

Maternal Serum ◽

Elective Cesarean Section ◽

Metabolic Markers ◽

Cord Serum ◽

Human Cerebrospinal Fluid ◽

Elective Cesarean ◽

Hypothalamic Tissue

Peripheral action of irisin improves glucose homeostasis and increases energy expenditure, with no data on a central role of irisin in metabolism. These studies sought to examine 1) presence of irisin in human cerebrospinal fluid (CSF) and banked human hypothalamic tissue, 2) serum irisin in maternal subjects across varying adiposities with or without gestational diabetes (GDM), and 3) their respective neonate offspring. CSF, serum, and neonatal cord serum were collected from 91 pregnant women with and without GDM attending for an elective cesarean section [body mass index (BMI): 37.7 ± 7.6 kg/m2; age: 32 ± 8.3 yr]. Irisin was assessed by ELISA and correlated with biochemical and anthropometric data. Irisin expression was examined in human hypothalamus by immunohistochemical staining. Serum irisin in pregnant women was significantly lower in nonobese compared with obese and GDM subjects, after adjusting for BMI, lipids, and glucose. Irisin was present in neonatal cord serum (237 ± 8 ng/ml) and maternal CSF (32 ± 1.5 ng/ml). CSF irisin correlated positively with serum irisin levels from nonobese and obese pregnant women ( P < 0.01), with CSF irisin significantly raised in GDM subjects ( P < 0.05). Irisin was present in human hypothalamic sections in the paraventricular neurons, colocalized with neuropeptide Y. Irisin was detectable in CSF and in paraventricular neurons. Maternal serum irisin was lower in nonobese pregnant women after adjusting for BMI and a number of metabolic parameters. These studies indicate that irisin may have a central role in metabolism in addition to the known peripheral role. Further studies investigating the central action of irisin in human metabolic disease are required.

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Do pregnant women prefer timing of elective cesarean section prior to versus after 39 weeks of gestation? Secondary analyses from a randomized controlled trial

The Journal of Maternal-Fetal & Neonatal Medicine ◽

10.3109/14767058.2013.879707 ◽

2014 ◽

Vol 27 (17) ◽

pp. 1782-1786 ◽

Cited By ~ 2

Author(s):

J. Glavind ◽

T. B. Henriksen ◽

S. F. Kindberg ◽

N. Uldbjerg

Keyword(s):

Randomized Controlled Trial ◽

Cesarean Section ◽

Pregnant Women ◽

Controlled Trial ◽

Elective Cesarean Section ◽

Randomized Controlled ◽

Elective Cesarean ◽

Secondary Analyses

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Fibrin monomer complex in normal pregnant women: a potential thrombotic marker in pregnancy

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/000456307781646076 ◽

2007 ◽

Vol 44 (5) ◽

pp. 449-454 ◽

Cited By ~ 19

Author(s):

Hiroaki Onishi ◽

Kimiko Kaniyu ◽

Mitsutoshi Iwashita ◽

Asashi Tanaka ◽

Takashi Watanabe

Keyword(s):

Pregnant Women ◽

Late Pregnancy ◽

Normal Pregnancy ◽

Reference Ranges ◽

Vein Thrombosis ◽

Fibrin Monomer ◽

Potential Marker ◽

Deep Vein ◽

Positive Results ◽

In Pregnancy

Background: Pregnancy represents a major risk factor for deep vein thrombosis (DVT). Most coagulation/fibrinolysis markers currently utilized change during pregnancy, and therefore they cannot accurately evaluate thrombotic events in pregnancy because the rate of false positive results is high. Fibrin monomer complex (FMC) has recently become widely available for diagnosing DVT. The present study examined whether FMC is suitable for evaluating thrombotic status in pregnancy. Methods: Concentrations of FMC and other haemostatic markers were investigated in 87 pregnant women without major complications at early, mid- or late pregnancy. FMC concentrations were also measured in 127 normal non-pregnant women, and in one woman who developed DVT after delivery. Results: In normal pregnant women, FMC concentrations were unchanged during early or mid-pregnancy and slightly elevated during late pregnancy. Concentrations were within reference range in most cases, and none exceeded the cut-off value for DVT. In contrast, thrombin-antithrombin complex (TAT) and D-dimer (DD) concentrations were significantly elevated in late pregnancy, and median values exceeded reference ranges. The DVT case displayed significantly elevated FMC concentrations. Conclusions: Changes in FMC concentrations during normal pregnancy are minimal compared with other haemostatic markers. Because the rate of false positivity is lower, FMC could be a potential marker of thrombotic status in pregnancy rather than TAT and DD.

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Pregnancy-associated and placental proteins in the placental tissue of normal pregnant women and patients with pre-eclampsia at term

Acta Endocrinologica ◽

10.1530/eje.0.1470785 ◽

2002 ◽

pp. 785-793 ◽

Cited By ~ 35

Author(s):

NA Bersinger ◽

N Groome ◽

S Muttukrishna

Keyword(s):

Pregnant Women ◽

Protein A ◽

Placental Tissue ◽

Serum Levels ◽

Activin A ◽

Placental Lactogen ◽

Compensatory Mechanism ◽

Protein Markers ◽

Inhibin A ◽

Placental Disease

OBJECTIVE: Pre-eclampsia is a placental disease of unknown cause. Maternal circulating concentrations of a number of protein markers are altered (mainly increased) in pre-eclampsia in comparison with controls of matched gestational age. Inhibin A and activin A were found to be elevated even before the onset of the disease. The aim of this study was to compare the levels of inhibin A, activin A: follistatin ratio, leptin, pregnancy-associated plasma protein-A (PAPP-A), human placental lactogen (HPL), placenta growth factor (PLGF) and pregnancy-specific beta1-glycoprotein (SP1) in placental extracts of normal pregnant women and pre-eclampsia patients at term. METHODS: Placental tissue from normal pregnancies (n=14) and patients with pre-eclampsia (n=13) were collected at term (> or =37 weeks of gestation) and stored at -80 degrees C. The frozen tissue pieces were homogenised and the above-mentioned proteins were measured by specific enzyme-linked immunosorbent assays. RESULTS: Placental contents of inhibin A and PAPP-A were significantly higher (P<0.05) in pre-eclampsia placental extracts compared with the controls. Activin A:follistatin ratio was higher (23) in pre-eclampsia extracts than in the controls (15). Leptin, PLGF, SP1 and HPL levels were not altered in the term pre-eclampsia placenta. Inhibin A and PAPP-A contents were increased in the placental extracts of pre-eclampsia patients. CONCLUSION: Our data suggest that the placenta, possibly by a compensatory mechanism, is at least in part responsible for the altered serum levels observed in pre-eclampsia.

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Hyperlipidemia in pregnancy

Orvosi Hetilap ◽

10.1556/oh.2011.29108 ◽

2011 ◽

Vol 152 (19) ◽

pp. 753-757 ◽

Cited By ~ 1

Author(s):

Tatjána Ábel ◽

Anna Blázovics ◽

Márta Kemény ◽

Gabriella Lengyel

Keyword(s):

Cardiovascular Disease ◽

Acute Pancreatitis ◽

Cohort Studies ◽

Pregnant Women ◽

Breast Feeding ◽

Normal Pregnancy ◽

Large Cohort ◽

Physiological Changes ◽

Teratogenic Effects ◽

In Pregnancy

Physiological changes in lipoprotein levels occur in normal pregnancy. Women with hyperlipoproteinemia are advised to discontinue statins, fibrates already when they consider pregnancy up to and including breast-feeding the newborn, because of the fear for teratogenic effects. Hypertriglyceridemia in pregnancy can rarely lead to acute pancreatitis. Management of acute pancreatitis in pregnant women is similar to that used in non-pregnant patients. Further large cohort studies are needed to estimate the consequence of supraphysiologic hyperlipoproteinemia or extreme hyperlipoproteinemia in pregnancy on the risk for cardiovascular disease later in life. Orv. Hetil., 2011, 152, 753–757.

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Association between abnormal maternal serum levels of vitamin B12 and preeclampsia: a systematic review and meta-analysis

Nutrition Reviews ◽

10.1093/nutrit/nuaa096 ◽

2020 ◽

Author(s):

Farzaneh Mardali ◽

Somaye Fatahi ◽

Maryam Alinaghizadeh ◽

Hamed Kord Varkaneh ◽

Mohammad Hassan Sohouli ◽

...

Keyword(s):

Systematic Review ◽

Vitamin B12 ◽

Pregnant Women ◽

Data Extraction ◽

Meta Analysis ◽

Serum Vitamin ◽

Serum Levels ◽

Folic Acid Supplementation ◽

Maternal Serum ◽

Study Selection

Abstract Context Some evidence has shown an association between maternal vitamin B12 levels and the development of preeclampsia in pregnant women, but the relationship between preeclampsia and vitamin B12 is not clear. Objective The aim of this systematic review was to compare serum vitamin B12 levels in women with preeclampsia with those in normotensive pregnant women. Data Sources The PubMed/MEDLINE, Scopus, and Web of Science databases were searched up to August 2019, along with the reference lists of included articles. Study Selection The literature was searched for observational studies that investigated vitamin B12 levels in women with preeclampsia. Data Extraction Data were extracted independently by 2 authors. Data were pooled using a random-effects model. Results Vitamin B12 levels in women with preeclampsia were significantly lower than those in healthy women (mean, −15.24 pg/mL; 95%CI, −27.52 to −2.954; P < 0.015), but heterogeneity between studies was high (I2 = 97.8%; P = 0.0103). Subgroup analyses based on folic acid supplementation, homocysteine concentrations, and gestational age at the time of sampling for vitamin B12 assessment did not identify the sources of heterogeneity. Conclusions Women with preeclampsia had significantly lower vitamin B12 concentrations than normotensive pregnant women.

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