Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the ...steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (
= 44) and GDM- women (
= 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.
Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. ...The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.
Insulin-like growth factors (IGFs) are involved in regulating growth and metabolism and increase insulin sensitivity, improve glucose metabolism, and are potentially related to gestational diabetes ...mellitus (GDM) and its complications for mothers and fetuses.
This study aimed to assess serum levels and cord blood levels of IGF system components in pregnant women with (39 participants) and without GDM (22 participants). Blood samples were obtained at 28–32 and 36–38 weeks of gestation and 6–12 months after delivery. Cord blood samples were obtained during delivery. Results between both groups as well as between single visits were statistically compared.
Both IGF1 and IGF2 maternal serum levels did not differ between the GDM and non-GDM groups. However, levels of IGF-binding proteins (IGFBPs) were different. IGFBP4 levels were decreased during pregnancy and after delivery in women with GDM, while IGFBP7 levels were increased during pregnancy in women with GDM. Cord blood IGFBP3 and IGFBP7 levels were increased (p < 0.001 for IGFBP3, p = 0.003 for IGFBP7), while IGFBP4 levels were decreased (p < 0.001) in the GDM group compared with the non-GDM group.
Although IGF levels did not differ, changes in their function level could still persist possibly because of the effects of the binding proteins, especially their promoting or inhibitory effects on IGFs. These results should be considered in interpretation of IGF levels.
•Both IGF1 and IGF2 maternal serum levels remained unchanged between the GDM and non-GDM groups.•GDM is associated with differences in the levels of IGFBP3, IGFBP4, and IGFBP7, which show differences in serum of women with GDM and cord blood of their infants in comparison to healthy pregnant women and their infants.•Although IGF levels were unchanged, they could exhibit changed activity levels due to interaction with binding proteins, which may be linked to the complications related to GDM.
Mannose‐binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro‐organisms, but also for efferocytosis. The aim of this study ...was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non‐pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%‐100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%‐97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%‐83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%‐83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.
Chronic inflammation has been implicated as the underlying mechanism responsible for the pathophysiology of preterm labor. Mannose-bindig lectin (MBL) plays a central role in the innate immune ...response and is thus an important component of the first line of defense. The aim of this study was to investigate whether serum concentrations of MBL correlated with the incidence of preterm birth and low birth weight in a cohort of women with signs of threatened preterm birth.
A cohort of 60 patients who presented with regular contractions and/or short cervix (group A) between 24 to 32 weeks of gestation and 20 healthy controls (group B) who had no pregnancy complications and delivered at term were recruited into a prospective study. The following outcomes were recorded : presence of preterm labor and birth weight in all patients. Mannose binding lectin (MBL) and high sensitivity C-reactive protein (hs-CRP) levels were measured in all serum samples.
The serum concentrations of MBL were significantly reduced in patients with threatened preterm labor (Group A), compared to the control Group B. Furthermore, infants born to Group A mothers with MBL deficiency (n = 13, MBL ≤ 100 ng/mL) had significantly lower birth weights, compared to those born to Group A women with normal MBL serum concentrations (p< 0.0001) CONCLUSIONS: Our small cohort study demonstrated a strong association between MBL deficiency and preterm delivery, and associated low birth weight. MBL deficiency could thus be considered an important risk factor for preterm birth. This article is protected by copyright. All rights reserved.
Pregnanolone isomers (PIs) and their polar conjugates (PICs) modulate ionotropic receptors such as gamma-aminobutyric acid or pregnane X receptors. Besides, brain synthesis, PI penetrates the ...blood-brain barrier. We evaluated the physiological importance of PI respecting the status of sex, menstrual cycle, and pregnancy. Accordingly, circulating levels of allopregnanolone (P3alpha 5alpha ), isopregnanolone (P3beta 5alpha ), pregnanolone (P3alpha 5beta ), epipregnanolone (P3beta 5beta ), their polar conjugates, and related steroids were measured in 15 men (M), 15 women in the follicular phase (F), 16 women in the luteal phase (L), and 30 women in the 36th week of gestation (P) using GC-MS. The steroid levels were similar in M and F, increased about thrice in L and escalated in P (38-410 times compared with F). The PICs were prevalent over the PIs (16-150 times). Higher ratios of 5alpha-PIC to 5alpha-PI found in P indicate the more intensive conjugation of 5alpha-PI during pregnancy. This mechanism probably provides for the elimination of neuroinhibitory P3alpha 5alpha in the maternal compartment. Additionally, our result points to a limited sulfation capacity for neuroinhibitory P3alpha 5beta in P. In contrast to the situation in M, F, and L where the P3alpha 5beta C is the most abundant PIC, and P3alpha 5beta is present in minor quantities compared with the P3alpha 5alpha, P3alpha 5beta may acquire physiological importance during pregnancy, contributing to the sustaining thereof. On the other hand, the declining formation of P3alpha 5beta may participate in the initiation of parturition, given the relative abundance of the steroid, its potency to suppress the activity of oxytocin-producing cells and its effectiveness in uterine relaxation.
The receptor for advanced glycation end products, RAGE, has been implicated in pathogenesis of many diseases. Soluble RAGE, sRAGE, extracellular domain of RAGE, is new biomarker. The aim of the study ...was to determine sRAGE levels in physiological pregnancy and their changes in pregnancies complicated by preterm labor or preeclampsia.
Serum levels of sRAGE were determined in 79 healthy pregnant women, 42 pregnant women in preterm labor or with preeclampsia and 24 non-pregnant controls.
sRAGE serum levels are decreased in physiological pregnancy compared to healthy non-pregnant controls (
p
<
0.001). Serum sRAGE concentrations are higher in the 2nd trimester of physiological pregnancy, compared to the 1st and 3rd trimesters of pregnancy (
p
<
0.001). sRAGE levels in women with preterm labor are decreased (
p
<
0.05) and correlate negatively with the leukocyte count (
r
=
-0.47,
p
<
0.05). In women with preeclampsia, sRAGE is elevated (
p
<
0.05) and correlates with serum creatinine concentration (
r
=
0.54,
p
<
0.05) and with uric acid concentration (
r
=
0.51,
p
<
0.05).
Our results clearly demonstrate significant differences in serum sRAGE levels in physiological pregnancy and in pathological states in pregnancy, however, further studies are required demonstrate the usefulness and significance of sRAGE.
This study addresses the question of whether changes in the biosynthesis and metabolism of neuroactive pregnanolone isomers (PIs) might participate in the timing of parturition in humans. The time ...profiles of unconjugated allopregnanolone (3α-hydroxy-5α-pregnan-20-one, P3α5α), pregnanolone (3α-hydroxy-5β-pregnan-20-one, P3α5β), isopregnanolone (3β-hydroxy-5α-pregnan-20-one, P3β5α) and epipregnanolone (3β-hydroxy-5β-pregnan-20-one, P3β5β), pregnenolone, their polar conjugates, progesterone, 5α-dihydroprogesterone (P5α), and 5β-dihydroprogesterone (P5β) were monitored in the plasma of 30 healthy women during the third trimester of pregnancy, at 1-week intervals from the 30th week of gestation using GC–MS. Changes in the steroid levels were evaluated by two-way ANOVA with gestational age and subject as independent factors. The mean concentrations of free PIs ranged from 2 to 50
nmol/L, while the mean levels of their polar conjugates were 40–100× higher. The ratio of 5α-PIs to progesterone significantly but inconspicuously culminated in the 35th week. The decelerating biosynthesis of free 5β-PIs from the 31st week and their escalating sulfation was found from the 30th week. The changes were particularly evident in the second most abundant PI pregnanolone that may, like the allopregnanolone, sustain the pregnancy via attenuation of hypothalamic GABA
A-receptors and prevent uterine contractility via binding to nuclear pregnane X receptor.
Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of ...liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.
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