Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery

Kothiyal, Prachi; Schulkers, Keriann; Hazrati, Sahel; Vilboux, Thierry; Gómez, Luis M.; Huddleston, Kathi; Wong, Wendy S. W.; Niederhuber, John E.; Conrads, Thomas P.; Maxwell, G. Larry; Hourigan, Suchitra K.

doi:10.1038/s41598-020-74989-8

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…Briefly, cesarean section has been associated with a number of inflammatory conditions in newborns, childhood, and adulthood and is considered to be an environmental risk factor for chronic immune and inflammatory diseases 42,43 . Cesarean delivery differs from vaginal delivery in terms of various factors such as the use of anesthetic agents and antibiotics, physiological effects on the newborn, and the postpartum hospital environment.…”

Section: Discussionmentioning

confidence: 99%

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Yerlikaya

Onmaz

Altunhan

et al. 2021

American J Rep Immunol

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Problem The cesarean section (CS) rate has increased significantly in North America, Western Europe, and Latin America. However, it has been reported that the incidence of inflammatory and autoimmune diseases such as asthma and type 1 diabetes increased in parallel with CS in these countries. Our aim was to investigate the expression level of miRNAs associated with inflammatory response and autoimmune diseases in colostrum samples and contribute to elucidating the role of CS in the pathogenesis of immune system–related diseases. Method of study Colostrum samples were taken from voluntary mothers who had 40 normal and 50 cesarean births. miRNAs were extracted from colostrums and detected to miRNA expression profiling (eighty‐four miRNAs) by quantitative real‐time PCR with the Fluidigm integrated microfluidic circuit technology. Results There was a statistically significant change in the expression levels of 17 miRNAs in the colostrums of mothers who had normal and cesarean delivery (p < .05), and all of miRNAs were upregulated in the colostrums of mothers who have had cesarean delivery. Conclusion Our best knowledge is that the study we conducted was the first to investigate the effect of delivery method (CS or normal) on the miRNA profile of colostrum. Cesarean delivery is a potential risk factor for inflammatory and immune system–related diseases in children due to dysregulation in miRNA expression.

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Section: Discussionmentioning

confidence: 99%

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Yerlikaya

Onmaz

Altunhan

et al. 2021

American J Rep Immunol

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“…Furthermore, in our analysis, we corrected for two major delivery variables which have been associated with placental gene expression at birth: delivery mode (i.e. C-section) [ 77 ] and induced labor [ 78 ]. The fact that we did not observe much remaining variability in placental gene expression after this correction could also indicate that gene expression in placenta at birth represents the state and circumstances of birth rather than any developmental processes.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in DNA methylation across gestation: a large scale, cross-cohort, multi-tissue analysis

Czamara,

Dieckmann,

Lahti-Pulkkinen

et al. 2024

Cell. Mol. Life Sci.

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Biological sex is a key variable influencing many physiological systems. Disease prevalence as well as treatment success can be modified by sex. Differences emerge already early in life and include pregnancy complications and adverse birth outcomes. The placenta is a critical organ for fetal development and shows sex-based differences in the expression of hormones and cytokines. Epigenetic regulation, such as DNA methylation (DNAm), may underlie the previously reported placental sexual dimorphism. We associated placental DNAm with fetal sex in three cohorts. Individual cohort results were meta-analyzed with random-effects modelling. CpG-sites differentially methylated with sex were further investigated regarding pathway enrichment, overlap with methylation quantitative trait loci (meQTLs), and hits from phenome-wide association studies (PheWAS). We evaluated the consistency of findings across tissues (CVS, i.e. chorionic villus sampling from early placenta, and cord blood) as well as with gene expression. We identified 10,320 epigenome-wide significant sex-differentially methylated probes (DMPs) spread throughout the epigenome of the placenta at birth. Most DMPs presented with lower DNAm levels in females. DMPs mapped to genes upregulated in brain, were enriched for neurodevelopmental pathways and significantly overlapped with meQTLs and PheWAS hits. Effect sizes were moderately correlated between CVS and placenta at birth, but only weakly correlated between birth placenta and cord blood. Sex differential gene expression in birth placenta was less pronounced and implicated genetic regions only marginally overlapped with those associated with differential DNAm. Our study provides an integrative perspective on sex-differential DNAm in perinatal tissues underscoring the possible link between placenta and brain.

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“…The adult-type definitive erythroid cell (EryD) expresses AQP9 [81]. The PI3 gene is expressed in the human placenta [82] and encodes trappin2/elafin, a key component of the innate immune system, which functions in antimicrobial and anti-inflammatory pathways [83,84].…”

Section: Discussionmentioning

confidence: 99%

Visual Analytics for Robust Investigations of Placental Aquaporin Gene Expression in Response to Maternal SARS-CoV-2 Infection

Isokpehi,

Abioye,

Hamilton

et al. 2024

Analytics

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The human placenta is a multifunctional, disc-shaped temporary fetal organ that develops in the uterus during pregnancy, connecting the mother and the fetus. The availability of large-scale datasets on the gene expression of placental cell types and scholarly articles documenting adverse pregnancy outcomes from maternal infection warrants the use of computational resources to aid in knowledge generation from disparate data sources. Using maternal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection as a case study in microbial infection, we constructed integrated datasets and implemented visual analytics resources to facilitate robust investigations of placental gene expression data in the dimensions of flow, curation, and analytics. The visual analytics resources and associated datasets can support a greater understanding of SARS-CoV-2-induced changes to the human placental expression levels of 18,882 protein-coding genes and at least 1233 human gene groups/families. We focus this report on the human aquaporin gene family that encodes small integral membrane proteins initially studied for their roles in water transport across cell membranes. Aquaporin-9 (AQP9) was the only aquaporin downregulated in term placental villi from SARS-CoV-2-positive mothers. Previous studies have found that (1) oxygen signaling modulates placental development; (2) oxygen tension could modulate AQP9 expression in the human placenta; and (3) SARS-CoV-2 can disrupt the formation of oxygen-carrying red blood cells in the placenta. Thus, future research could be performed on microbial infection-induced changes to (1) the placental hematopoietic stem and progenitor cells; and (2) placental expression of human aquaporin genes, especially AQP9.

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Differences in maternal gene expression in Cesarean section delivery compared with vaginal delivery

Cited by 8 publications

References 42 publications

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Can altered colostrum miRNA expression profile after cesarean delivery be a risk factor for autoimmune diseases?

Sex differences in DNA methylation across gestation: a large scale, cross-cohort, multi-tissue analysis

Visual Analytics for Robust Investigations of Placental Aquaporin Gene Expression in Response to Maternal SARS-CoV-2 Infection

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