Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress

Hosni, Ahmed; El-Twab, Sanaa Abd; Abdul-Hamid, Manal; Prinsen, Els; AbdElgawad, Hamada; Abdel-Moneim, Adel; Beemster, Gerrit T.S.

doi:10.1016/j.phrs.2021.105426

Cited by 15 publications

(12 citation statements)

References 99 publications

(145 reference statements)

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“…Further, it has been reported [ 12 , 13 ] that reactive oxygen species can directly damage the systolic function of the heart. Excessive glucose may cause fetal hyperinsulinemia, which may lead to a decrease in fetal blood oxygen levels [ 14 ]. Fetal hypoxia is accompanied by a surge in the levels of adrenaline and catecholamines, which cause heart remodeling and hypertrophy, resulting in abnormal fetal cardiac function [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study

Wang

Liu

et al. 2021

Cardiovasc Ultrasound

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Background Due to metabolic changes in the second trimester and the increasing number of pregnant women with obesity and advanced maternal age, the incidence of gestational diabetes mellitus (GDM) remains high. This study aimed to evaluate the effects of GDM on fetal cardiac morphology and function, and to determine whether these changes increase with increasing estimated fetal weight (EFW). Methods Fifty-eight women with GDM (GDM group) and 58 women with a healthy pregnancy (control group) were included in this prospective observational cohort study. Each group included subgroups of 31 pregnant women with a gestational age between 24+0 weeks and 27+6 weeks as well as 27 pregnant women with a gestational age between 28+0 weeks and 40+0 weeks. For all fetuses, a cine of 2–3 s in the four-chamber view was obtained, and online speckle-tracking analysis was performed using the GE Automatic Fetal Heart Assessment Tool (fetal HQ; General Electric Healthcare Ultrasound, Zipf, Austria) to measure the global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC), 24-segment sphericity index (SI), and 24-segment end-diastolic diameter of the left ventricle (LV) and right ventricle (RV). Data were analyzed using the independent t-test and Wilcoxon rank-sum test, as applicable. Results The GDM group (mean HbA1c value was 5.3 ± 0.57 mmol/L) showed a lower GSI value than the control group (1.21 vs. 1.27, P = 0.000), which indicated a rounder shape of the heart. In addition, fetuses in the GDM group demonstrated significant impairment in cardiac function compared to those in the control group (LV-GLS: -18.26% vs. -22.70%, RV-GLS: -18.52% vs. -22.74%, LV-FAC: 35.30% vs. 42.36%, RV-FAC: 30.89% vs. 36.80%; P = 0.000 for all). Subgroup analyses according to gestational age (24+0–27+6 weeks and 28+0–40+0 weeks) showed that the statistical differences were retained between the GDM and control groups in each subgroup. Conclusions Fetuses of women with GDM present with signs of biventricular systolic dysfunction according to deformation analysis using fetal HQ. Additionally, the heart had a rounder shape in the GDM group than in the control group. This study showed that fetal HQ can be used to assess fetal cardiac morphology and function easily and quickly, and the effects of GDM on fetal cardiac morphology and function appeared from the second trimester. Thus, whether earlier and stricter clinical intervention was necessary remained to be further studied. Furthermore, future studies will need to supplement the effects of blood glucose levels on GLS, FAC, GSI, and 24-segment SI. Additionally, the long-term follow-up after birth should also be improved to observe the influence of changes in the indicators on the prognosis.

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Section: Discussionmentioning

confidence: 99%

Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study

Wang

Liu

et al. 2021

Cardiovasc Ultrasound

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“…GDM patients who do not have significant high-risk lifestyle habits do not usually show obvious signs of disease. Without effective control, both the fetus and the pregnant mother are affected, with outcomes including fetal anemia, high levels of serum erythropoietin, and other abnormal manifestations [ 31 ]. In severe cases, GDM greatly reduces fetal quality of life and threatens the mother's life.…”

Section: Gdm and Vegfmentioning

confidence: 99%

Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia

Bolatai

2022

J Transl Med

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Background An imbalance in the expression of vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) during pregnancy plays an important role in the pathogenesis of gestational diabetes mellitus (GDM) and eclampsia. VEGF and its receptors change during the regulation of blood vessels as a result of risk factors such as familial genetics. These modifications include loss of original balance of serological indicators, upregulation or downregulation of growth factor indicators, and changes in the placenta, kidney, liver and other organs to varying degrees of damage. This has an impact on both the pregnant woman's and the fetus's health. Main body This paper summarizes the mechanisms of unbalanced VEGF and receptor expression based on data from relevant literature on GDM and eclampsia. An Imbalance in VEGF and its binding receptor is often associated with the occurrence of multiple pregnancy disorders. In recent years, researchers have focused on the potential role of VEGF and its receptors in the development of GDM and eclampsia. Conclusion This paper summarizes the different VEGF subtypes and their binding receptors, as well as mechanisms that cause GDM and eclampsia, in order to provide valuable data to inform monitoring, diagnosis, and prognosis.

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“…Human and rodent placentas are villous placentas, including syncytiotrophoblast and cytotrophoblast cells, which form the maternal–fetal barrier of villous tissue, thus effectively regulating the transfer and circulation of nutrients from mother to fetus [ 33 ]. By establishing a rat GDM model, a recent study has demonstrated that cinnamaldehyde alleviates placental structural abnormalities [ 25 ]. However, the effects of probiotics in this area remain unknown.…”

Section: Discussionmentioning

confidence: 99%

“…The pancreatic and hepatic tissues of rats with HIP were fixed in 4% formaldehyde (Beijing Changhua Zhicheng Technology Co., Ltd., Beijing, China) and embedded in paraffin for hematoxylin–eosin (H&E) staining, using standard protocols and histological scoring criteria [ 24 , 25 ].…”

Section: Methodsmentioning

confidence: 99%

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Ameliorative Effects of Bifidobacterium animalis subsp. lactis J-12 on Hyperglycemia in Pregnancy and Pregnancy Outcomes in a High-Fat-Diet/Streptozotocin-Induced Rat Model

Yang

et al. 2022

Nutrients

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Bifidobacterium, a common probiotic, is widely used in the food industry. Hyperglycemia in pregnancy has become a common disease that impairs the health of the mother and can lead to adverse pregnancy outcomes, such as preeclampsia, macrosomia, fetal hyperinsulinemia, and perinatal death. Currently, Bifidobacterium has been shown to have the potential to mitigate glycolipid derangements. Therefore, the use of Bifidobacterium-based probiotics to interfere with hyperglycemia in pregnancy may be a promising therapeutic option. We aimed to determine the potential effects of Bifidobacterium animalis subsp. lactis J-12 (J-12) in high-fat diet (HFD)/streptozotocin (STZ)-induced rats with hyperglycemia in pregnancy (HIP) and respective fetuses. We observed that J-12 or insulin alone failed to significantly improve the fasting blood glucose (FBG) level and oral glucose tolerance; however, combining J-12 and insulin significantly reduced the FBG level during late pregnancy. Moreover, J-12 significantly decreased triglycerides and total cholesterol, relieved insulin and leptin resistance, activated adiponectin, and restored the morphology of the maternal pancreas and hepatic tissue of HIP-induced rats. Notably, J-12 ingestion ameliorated fetal physiological parameters and skeletal abnormalities. HIP-induced cardiac, renal, and hepatic damage in fetuses was significantly alleviated in the J-12-alone intake group, and it downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health. Furthermore, placental tissue damage in rats with HIP appeared to be in remission in the J-12 group. Upon exploring specific placental microbiota, we observed that J-12 affected the abundance of nine genera, positively correlating with FBG and leptin in rats and hippocampal mRNA levels of InsR and IGF-1R mRNA in the fetus, while negatively correlating with adiponectin in rats and hippocampal levels of AKT in the fetus. These results suggest that J-12 may affect the development of the fetal central nervous system by mediating placental microbiota via the regulation of maternal-related indicators. J-12 is a promising strategy for improving HIP and pregnancy outcomes.

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Cinnamaldehyde mitigates placental vascular dysfunction of gestational diabetes and protects from the associated fetal hypoxia by modulating placental angiogenesis, metabolic activity and oxidative stress

Cited by 15 publications

References 99 publications

Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study

Evaluation of prenatal changes in fetal cardiac morphology and function in maternal diabetes mellitus using a novel fetal speckle-tracking analysis: a prospective cohort study

Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia

Ameliorative Effects of Bifidobacterium animalis subsp. lactis J-12 on Hyperglycemia in Pregnancy and Pregnancy Outcomes in a High-Fat-Diet/Streptozotocin-Induced Rat Model

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