scholarly journals Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation

2019 ◽  
Vol 2 (2) ◽  
pp. e201800252 ◽  
Author(s):  
Alexander M Tseng ◽  
Amanda H Mahnke ◽  
Alan B Wells ◽  
Nihal A Salem ◽  
Andrea M Allan ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Epithelial Mesenchymal Transition ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Growth Restriction ◽  
Circulating Mirnas ◽  
Placental Development ◽  
Mesenchymal Transition ◽  
Pregnant Mice

Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following PAE. Here, we investigated whether theseHEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial–mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and thatHEamiRNAs collectively, but not individually, mediate placental EMT inhibition.HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intravascular administration of the pooled murine-expressedHEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest thatHEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.

scholarly journals Maternal Circulating MiRNAs That Predict Infant FASD Outcomes Influence Placental Maturation

2018 ◽  
Author(s):  
Alexander M. Tseng ◽  
Amanda H. Mahnke ◽  
Alan B. Wells ◽  
Nihal A. Salem ◽  
Andrea M. Allan ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Epithelial Mesenchymal Transition ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Growth Restriction ◽  
Circulating Mirnas ◽  
Placental Development ◽  
Mesenchymal Transition ◽  
Prenatal Alcohol

AbstractPrenatal Alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, though the linking causal mechanisms are unclear. We previously identified 11 gestationally-elevated maternal circulating miRNAs that predicted infant growth deficits following PAE. Here, we investigated whether theseHEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time, that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and thatHEamiRNAs collectively, but not individually, mediate placental EMT inhibition.HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intra-vascular administration of the pooled murine-expressedHEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited expression of pro-EMT transcripts in placenta. Our data suggests thatHEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.SummaryMaternal gestational circulating microRNAs, predictive of adverse infant outcomes including growth deficits, following prenatal alcohol exposure, contribute to placental pathology by impairing the EMT pathway in trophoblasts.

Diabetes and pre-eclampsia affecting pregnancy: a retrospective cross-sectional study

2017 ◽  
Vol 66 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Ram R Kalagiri ◽  
Niraj Vora ◽  
Jessica L Wilson ◽  
Syeda H Afroze ◽  
Venkata N Raju ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cross Sectional Study ◽  
Growth Restriction ◽  
Sectional Study ◽  
Placental Development ◽  
Cross Sectional ◽  
Diabetes Status ◽  
Elevated Glucose ◽  
Post Hoc

The interaction between pre-eclampsia and diabetes mellitus (DM) is far from being completely understood. In this study, we compared normal pregnancies with those complicated with pre-eclampsia, gestational DM, and/or pre-existing diabetes to assess the effects of hyperglycemia on placental development. AnInstitutional Review Board (IRB) approved retrospective cross-sectional study with 621 subjects was performed. Statistical analysis was performed using Duncan’s post hoc test and analysis of variance. Regardless of diabetes status, patients with pre-eclampsia delivered prematurely. Patients in the group with pre-eclampsia and pregestational diabetes delivered much earlier, at 35.0±0.4 weeks, when compared with the patients that had pre-eclampsia with gestational diabetes and pre-eclampsia with no diabetes (*P<0.05 for each). Additionally, patients with pre-existing diabetes who developed pre-eclampsia delivered smaller babies than those with pre-existing diabetes without pre-eclampsia (1.00±0.03, P<0.05 for each). Pre-existing diabetes with added insult of pre-eclampsia led to fetal growth restriction. This outcome validates the understanding that elevated glucose earlier in pregnancy alters placentogenesis and leads to fetal growth restriction.

Development of Structures and Transport Functions in the Mouse Placenta

Physiology ◽  
2005 ◽  
Vol 20 (3) ◽  
pp. 180-193 ◽  
Author(s):  
Erica D. Watson ◽  
James C. Cross
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Cell Biology ◽  
Fetal Death ◽  
Nutrient Transport ◽  
Growth Restriction ◽  
Molecular Pathways ◽  
Placental Development ◽  
Mouse Mutants ◽  
Mouse Placenta

The placenta is essential for sustaining the growth of the fetus during gestation, and defects in its function result in fetal growth restriction or, if more severe, fetal death. Several molecular pathways have been identified that are essential for development of the placenta, and mouse mutants offer new insights into the cell biology of placental development and physiology of nutrient transport.

scholarly journals Effects of excess thromboxane A2 on placental development and nutrient transporters in a Mus musculus model of fetal growth restriction†

2018 ◽  
Vol 98 (5) ◽  
pp. 695-704 ◽  
Author(s):  
Karen J Gibbins ◽  
Katherine N Gibson-Corley ◽  
Ashley S Brown ◽  
Matthew Wieben ◽  
Richard C Law ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Mus Musculus ◽  
Fetal Growth Restriction ◽  
Thromboxane A2 ◽  
Growth Restriction ◽  
Nutrient Transporters ◽  
Placental Development

scholarly journals Cigarette exposure induces changes in maternal vascular function in a pregnant mouse model

2010 ◽  
Vol 298 (5) ◽  
pp. R1249-R1256 ◽  
Author(s):  
Robin E. Gandley ◽  
Arun Jeyabalan ◽  
Ketaki Desai ◽  
Stacy McGonigal ◽  
Jennifer Rohland ◽  
...  
Keyword(s):  
Mouse Model ◽  
Cigarette Smoke ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Smoke Exposure ◽  
Renal Arteries ◽  
Growth Restriction ◽  
Whole Body ◽  
Cigarette Smoke Exposure ◽  
Pregnant Mice

Smoking is associated with multiple adverse pregnancy outcomes, including fetal growth restriction. The objective of this study was to determine whether cigarette smoke exposure during pregnancy in a mouse model affects the functional properties of maternal uterine, mesenteric, and renal arteries as a possible mechanism for growth restriction. C57Bl/CJ mice were exposed to whole body sidestream smoke for 4 h/day. Smoke particle exposure was increased from day 4 of gestation until late pregnancy ( day 16–19), with mean total suspended particle levels of 63 mg/m3, representative of moderate-to-heavy smoking in humans. Uterine, mesenteric, and renal arteries from late-pregnant and virgin mice were isolated and studied in a pressure-arteriograph system ( n = 23). Plasma cotinine was measured by ELISA. Fetal weights were significantly reduced in smoke-exposed compared with control fetuses (0.88 ± 0.1 vs. 1.0 ± 0.08 g, P < 0.02), while litter sizes were not different. Endothelium-mediated relaxation responses to methacholine were significantly impaired in both the uterine and mesenteric vasculature of pregnant mice exposed to cigarette smoke during gestation. This difference was not apparent in isolated renal arteries from pregnant mice exposed to cigarette smoke; however, relaxation was significantly reduced in renal arteries from smoke-exposed virgin mice. In conclusion, we found that passive cigarette smoke exposure is associated with impaired vascular relaxation of uterine and mesenteric arteries in pregnant mice. Functional maternal vascular perturbations during pregnancy, specifically impaired peripheral and uterine vasodilation, may contribute to a mechanism by which smoking results in fetal growth restriction.

scholarly journals Levels of miR-374 increase in BeWo b30 cells exposed to hypoxia

2021 ◽  
Author(s):  
EN Knyazev ◽  
SYu Paul
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Target Genes ◽  
Expression Profiles ◽  
Growth Restriction ◽  
Trophoblast Invasion ◽  
Placental Development ◽  
Cell Potential ◽  
Bewo B30 ◽  
Next Generation Sequencing Ngs

In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia.

Sign in / Sign up

Export Citation Format

Share Document