Dysregulation of inflammatory cytokines and inhibition of VEGFA in the human umbilical cord are associated with negative pregnancy outcomes

Chehroudi, Camron; Kim, Hugh; Wright, Tricia E.; Collier, Abby C.

doi:10.1016/j.placenta.2019.09.002

Cited by 12 publications

(8 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This inflammatory environment at the delivery day could be the reason why we found higher levels of IL-1β and TNF-α in UCP than in the MP. This result is in line with a recent report stablishing that fetal-placental variables are directly associated with changes in the CKs present in UCP [ 38 ]. A successful pregnancy needs these pro-inflammatory events, but it is well known that an overexpression of pro-inflammatory CKs can disrupt fetal and placental developmental pathways [ 3 ] and can promote pre-term parturition or other delivery disorders [ 10 ].…”

Section: Discussionsupporting

confidence: 93%

“…The most important finding is that CKs, mainly the pro-inflammatory ones (IFN- γ, IL-1β, IL-6, IL-12, IL-17, and TNF-α), were decreased in the Enterotype II group at the day of delivery. These results are in line with the fact that pro-inflammatory CKs play an important role in a normal parturition [ 3 , 11 , 38 ]. However, it has to be taken into account that the cesarean delivery proportion is higher in this enterotype, and in this situation, high levels of these CKs could not be required.…”

Section: Discussionsupporting

confidence: 79%

“…On the other hand, the under-expression of those CKs is associated with adverse pregnancy outcomes. For example, Chehroudi et al observed lower levels of IL-1β, IL-6, and TNF-α in umbilical cord lysates at birth in mothers suffering from pre-eclampsia and gonococcus infection [ 38 ]. They also observed a decrease in IL-10 concentration.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles

Rio-Aigé

Azagra-Boronat

Massot-Cladera

et al. 2021

IJMS

View full text Add to dashboard Cite

Mothers confer natural passive immunization to their infants through the transplacental pathway during the gestation period. The objective of the present study was to establish at birth the maternal and cord plasma concentration and relationship of immunoglobulins (Igs), cytokines (CKs), and adipokines. In addition, the impact of the maternal microbiota and diet was explored. The plasma profile of these components was different between mothers and babies, with the levels of many CKs, IgM, IgG2a, IgE, IgA, and leptin significantly higher in mothers than in the cord sample. Moreover, the total Igs, all IgG subtypes, IgE, and the Th1/Th2 ratio positively correlated in the mother–infant pair. Maternal dietary components such as monounsaturated fatty acids-polyunsaturated fatty acids and fiber were positively associated with some immune factors such as IgA in cord samples. The microbiota composition clustering also influenced the plasma profile of some factors (i.e., many CKs, some Ig, and adiponectin). In conclusion, we have established the concentration of these immunomodulatory factors in the maternal–neonatal pair at birth, some positive associations, and the influence of maternal diet and the microbiota composition, suggesting that the immune status during pregnancy, in terms of CKs and Igs levels, can influence the immune status of the infant at birth.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 79%

See 1 more Smart Citation

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles

Rio-Aigé

Azagra-Boronat

Massot-Cladera

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…32) VEGFA gene can be induced by hypoxia, inflammatory cytokines, and oncogenes. 33,34) Thus, we suspected that VEGFA can regulate the viability of cardiomyocytes damaged by hypoxia by inducing cell apoptosis and promoting cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

MiR-448-5p/VEGFA Axis Protects Cardiomyocytes from Hypoxia Through Regulating the FAS/FAS-L Signaling Pathway

et al. 2021

View full text Add to dashboard Cite

Bioinformatics analysis showed that miR-448-5p expression in the myocardial tissue of rats with myocardial infarction significantly increased, suggesting that it may participate in myocardial cell apoptosis in myocardial infarction. This study aimed to explore the protective effects of miR-448-5p on hypoxic myocardial cells.H9C2 cells were cultured and subjected to anoxia for 2, 4, and 8 hours to establish a hypoxia model. MiR-448-5p mimic and inhibitor were transfected into the cells; then, a dual-luciferase experiment was conducted to verify the targeting relationship between miR-448-5p and VEGFA. Cell viability and apoptosis was detected by cell counting kit-8 and flow cytometry, respectively. The expressions of apoptosis-related proteins, miR-448-5p, FAS, and FAS-L were measured using western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Hypoxia-reduced H9C2 cell viability and promoted apoptosis. MiR-448-5p expression was increased after H9C2 cell hypoxia. MiR-448-5p mimic significantly inhibited the viability and promoted the apoptosis of hypoxia-induced model cells. Hypoxia promoted the expression of apoptosis-related protein B-cell lymphoma-2 (Bcl-2) and inhibited the expressions of Bcl-2-associated x protein (Bax), cleaved caspase-3, and caspase-3, whereas the effect of inhibitor on hypoxia-reduced H9C2 cell and apoptotic protein expression were opposite to miR-448-5p mimic. MiR-448-5p targeted VEGFA and regulated its expression. Silenced VEGFA expression significantly inhibited inhibitor effect on increasing cell viability and promoted apoptosis. In addition, miR-448-5p mimic inhibited the effect of hypoxia on promoting the expressions of FAS and FAS-L of H9C2 cells. Inhibitors had the opposite effect on cell hypoxia model.The miR-448-5p/VEGFA axis could protect cardiomyocytes from hypoxia through inhibiting the FAS/FAS-L signaling pathway.

show abstract

“…Presence of a drug in fetal tissues demonstrates that some level of exposure is occurring, but there are no currently defined dose:concentration relationships that would make this process predictive of maternal ingestion or absolute fetal exposure levels. With our prior experience using reproductive tissues for detection and quantification of drugs, endo- and xenobiotics and their effects on reproductive outcomes [ [31] , [32] , [33] , [34] , [35] , [36] ], we developed the hypothesis that UC would be a reliable matrix for detecting NSAID use, more reflective of fetal NSAID exposure than maternal blood alone. In this study, we retrospectively screened 380 UC lysates for five of the most commonly used NSAIDs: diclofenac, ibuprofen, indomethacin, naproxen, and salicylic acid, to determine maternal ingestion of these drugs close to birth, fetal exposure, and relationships (if any) between NSAID use and obstetric and neonatal outcomes.…”

Section: Introductionmentioning

confidence: 99%

Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Dysregulation of inflammatory cytokines and inhibition of VEGFA in the human umbilical cord are associated with negative pregnancy outcomes

Cited by 12 publications

References 46 publications

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles

Association of Maternal Microbiota and Diet in Cord Blood Cytokine and Immunoglobulin Profiles

MiR-448-5p/VEGFA Axis Protects Cardiomyocytes from Hypoxia Through Regulating the FAS/FAS-L Signaling Pathway

Detection and quantitation of non-steroidal anti-inflammatory drug use close to the time of birth using umbilical cord tissue

Contact Info

Product

Resources

About