Intrauterine growth restriction-induced deleterious adaptations in endothelial progenitor cells: possible mechanism to impair endothelial function

2017 ◽  
Vol 8 (6) ◽  
pp. 665-673 ◽  
Author(s):  
V. Oliveira ◽  
L. V. de Souza ◽  
T. Fernandes ◽  
S. D. S. Junior ◽  
M. H. C. de Carvalho ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Functional Capacity ◽  
Intrauterine Growth Restriction ◽  
Vascular Reactivity ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Ad Libitum

Intrauterine growth restriction (IUGR) can induce deleterious changes in the modulatory ability of the vascular endothelium, contributing to an increased risk of developing cardiovascular diseases in the long term. However, the mechanisms involved are not fully understood. Emerging evidence has suggested the potential role of endothelial progenitor cells (EPCs) in vascular health and repair. Therefore, we aimed to evaluate the effects of IUGR on vascular reactivity and EPCs derived from the peripheral blood (PB) and bone marrow (BM)in vitro. Pregnant Wistar rats were fed anad libitumdiet (control group) or 50% of thead libitumdiet (restricted group) throughout gestation. We determined vascular reactivity, nitric oxide (NO) concentration, and endothelial nitric oxide synthase (eNOS) protein expression by evaluating the thoracic aorta of adult male offspring from both groups (aged: 19–20 weeks). Moreover, the amount, functional capacity, and senescence of EPCs were assessedin vitro. Our results indicated that IUGR reduced vasodilation via acetylcholine in aorta rings, decreased NO levels, and increased eNOS phosphorylation at Thr495. The amount of EPCs was similar between both groups; however, IUGR decreased the functional capacity of EPCs from the PB and BM. Furthermore, the senescence process was accelerated in BM-derived EPCs from IUGR rats. In summary, our findings demonstrated the deleterious changes in EPCs from IUGR rats, such as reduced EPC function and accelerated senescencein vitro. These findings may contribute towards elucidating the possible mechanisms involved in endothelial dysfunction induced by fetal programming.

scholarly journals Human Cytomegalovirus Infection Interferes with the Maintenance and Differentiation of Trophoblast Progenitor Cells of the Human Placenta

2015 ◽  
Vol 89 (9) ◽  
pp. 5134-5147 ◽  
Author(s):  
Takako Tabata ◽  
Matthew Petitt ◽  
Martin Zydek ◽  
June Fang-Hoover ◽  
Nicholas Larocque ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Human Cytomegalovirus ◽  
Intrauterine Growth Restriction ◽  
Molecular Mechanisms ◽  
Hcmv Infection ◽  
Congenital Infection ◽  
Growth Restriction ◽  
Chorionic Villi ◽  
Intrauterine Growth

ABSTRACTHuman cytomegalovirus (HCMV) is a major cause of birth defects that include severe neurological deficits, hearing and vision loss, and intrauterine growth restriction. Viral infection of the placenta leads to development of avascular villi, edema, and hypoxia associated with symptomatic congenital infection. Studies of primary cytotrophoblasts (CTBs) revealed that HCMV infection impedes terminal stages of differentiation and invasion by various molecular mechanisms. We recently discovered that HCMV arrests earlier stages involving development of human trophoblast progenitor cells (TBPCs), which give rise to the mature cell types of chorionic villi—syncytiotrophoblasts on the surfaces of floating villi and invasive CTBs that remodel the uterine vasculature. Here, we show that viral proteins are present in TBPCs of the chorion in cases of symptomatic congenital infection.In vitrostudies revealed that HCMV replicates in continuously self-renewing TBPC lines derived from the chorion and alters expression and subcellular localization of proteins required for cell cycle progression, pluripotency, and early differentiation. In addition, treatment with a human monoclonal antibody to HCMV glycoprotein B rescues differentiation capacity, and thus, TBPCs have potential utility for evaluation of the efficacies of novel antiviral antibodies in protecting and restoring placental development. Our results suggest that HCMV replicates in TBPCs in the chorionin vivo, interfering with the earliest steps in the growth of new villi, contributing to virus transmission and impairing compensatory development. In cases of congenital infection, reduced responsiveness of the placenta to hypoxia limits the transport of substances from maternal blood and contributes to fetal growth restriction.IMPORTANCEHuman cytomegalovirus (HCMV) is a leading cause of birth defects in the United States. Congenital infection can result in permanent neurological defects, mental retardation, hearing loss, visual impairment, and pregnancy complications, including intrauterine growth restriction, preterm delivery, and stillbirth. Currently, there is neither a vaccine nor any approved treatment for congenital HCMV infection during gestation. The molecular mechanisms underlying structural deficiencies in the placenta that undermine fetal development are poorly understood. Here we report that HCMV replicates in trophoblast progenitor cells (TBPCs)—precursors of the mature placental cells, syncytiotrophoblasts and cytotrophoblasts, in chorionic villi—in clinical cases of congenital infection. Virus replication in TBPCsin vitrodysregulates key proteins required for self-renewal and differentiation and inhibits normal division and development into mature placental cells. Our findings provide insights into the underlying molecular mechanisms by which HCMV replication interferes with placental maturation and transport functions.

Melatonin-MT1 signal is essential for endometrial decidualization

Reproduction ◽  
2021 ◽  
Author(s):  
Liyuan Cui ◽  
Feng Xu ◽  
Songcun Wang ◽  
Zhuxuan Jiang ◽  
Lu Liu ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Endometrial Stromal Cells ◽  
Reproductive Process ◽  
Intrauterine Growth ◽  
In Vivo Experiments ◽  
Adverse Pregnancy

Deficient decidualization of endometrial stromal cells (ESCs) can cause adverse pregnancy outcomes including miscarriage, intrauterine growth restriction and pre-eclampsia. Decidualization is regulated by multiple factors such as hormones and circadian genes. Melatonin, a circadian-controlled hormone, is reported to be important for various reproductive process, including oocyte maturation and placenta development. Its receptor, MT1, is considered to be related to intrauterine growth restriction and pre-eclampsia. However, the role of melatonin-MT1 signal in decidualization remains unknown. Here, we reported that decidual stromal cells from miscarriages displayed deficient decidualization with decreased MT1 expression. The expression level of MT1 is gradually increased with the process of decidualization induction in vitro. MT1 knockdown suppressed decidualization level, while overexpression of MT1 promoted the decidualization process. Moreover, changing MT1 level could regulate the expression of decidualization-related transcription factor FOXO1. Melatonin promoted decidualization and reversed the decidualization deficiency due to MT1 knockdown. Using in vitro and in vivo experiments, we further identified that lipopolysaccharide (LPS) could induce inflammation and decidualization resistance with downregulated MT1 expression, and melatonin could reverse the inflammation and decidualization resistance induced by LPS. These results suggested melatonin-MT1 signal might be essential for decidualization and might provide a novel therapeutic target for decidualization deficiency-associated pregnancy complications.

scholarly journals Whey Versus Casein as a Protein Source during the Weaning Period: Impact on Growth and Later Adiposity and Glucose Homeostasis in a Rat Model of Intrauterine Growth Restriction

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3399
Author(s):  
Yasaman Shahkhalili ◽  
Florence Blancher-Budin ◽  
Cathriona Monnard ◽  
Julie Moulin ◽  
José Sanchez-Garcia ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Intrauterine Growth Restriction ◽  
Early Life ◽  
Growth Restriction ◽  
Protein Source ◽  
Intrauterine Growth ◽  
Populations At Risk ◽  
Ad Libitum ◽  
The Impact

The impact of early life protein source (whey vs. casein) on short- and long-term glucose homeostasis and adiposity is unknown and was investigated in this study. At the end of the suckling period, non-IUGR (intrauterine growth restriction) and IUGR pups were separated from dams and were randomized into four groups. From age 21–49 days, non-IUGR and IUGR pups were fed ad-libitum chow or a semi-synthetic diet (20% from protein; casein or whey) and from age 50–199 days, all groups were fed ad-libitum chow. Food intake, body composition, glucose, and insulin homeostasis were assessed. Among the chow groups, IUGR had slower growth and higher fasting glucose at age 42 days, as well as higher fasting and AUC glucose at age 192 days relative to non-IUGR. The whey IUGR group had a slower growth rate and higher fasting glycemia in early life (age 21–49 days) and higher HOMA-IR later in life (age 120–122 and 190–192 days) relative to casein IUGR. This study shows the potential advantage of casein relative to whey during weaning on short term energy intake, growth, and glucose homeostasis in an IUGR model and reveals, for the first time, its long term impact on insulin sensitivity, which may have implications for later metabolic health, particularly in small-for-gestational-age populations at risk of type 2 diabetes.

Neurokinin B and nitric oxide plasma levels in pre-eclampsia and isolated intrauterine growth restriction

2004 ◽  
Vol 111 (10) ◽  
pp. 1046-1050 ◽  
Author(s):  
Rosario D'Anna ◽  
Giovanni Baviera ◽  
Francesco Corrado ◽  
Alessandra Crisafulli ◽  
Riccardo Ientile ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Plasma Levels ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Neurokinin B ◽  
Intrauterine Growth
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