Advances in the role of oxytocin receptors in human parturition

Kim, Sung Hye; Bennett, Phillip R.; Terzidou, Vasso

doi:10.1016/j.mce.2017.01.034

Cited by 50 publications

(38 citation statements)

References 95 publications

(91 reference statements)

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“…This result was also observed for the GpC ODN control. While the results presented in this study do not define the mechanism responsible for this effect, a reasonable suggestion is that GpC ODN may interfere with the role of oxytocin receptor in activating non‐specific inflammatory pathways, regulation of miRNA expression, as well as the crosstalk between oxytocin and G protein‐coupled receptors . Another possibility is that CpG and GpC motifs function as utero‐relaxant agents independent of TLR9, which is in line with previous in‐vitro observations that GpC ODN acting through TLR7 displayed immunosuppressive properties by allowing plasmacytoid dentritic cells to assist with generation of FOXP3+ T cells .…”

Section: Discussionsupporting

confidence: 84%

Toll‐like receptor 9, maternal cell‐free DNA and myometrial cell response to CpG oligodeoxynucleotide stimulation

Beck

Buhimschi

Summerfield

et al. 2019

American J Rep Immunol

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Problem: Among mechanisms triggering onset of parturition, it has been recently postulated that Toll-Like Receptor (TLR)9 engagement by cell-free DNA (cfDNA) triggers inflammation, myometrial contractions, and labor in absence of infection. The current study evaluated whether direct (myometrial) or indirect (decidual) TLR9 engagement enhances human myometrial contractility. Method of Study:Toll-like receptor 9 expression and cellular localization were surveyed by immunohistochemistry of placenta, fetal membranes, and myometrium in term (gestational age [GA]: >37 weeks) labor (TL, n = 7) or term non-labor (TNL, n = 7)tissues. Non-pregnant myometrium (n = 4) served as reference. TLR9 mRNA expression relative to other TLRs was evaluated through the mining of an RNA-seq dataset and confirmed by RT-PCR. Immortalized human myometrial cells (hTERT-HM) were treated with incremental concentrations of TLR9 agonist ODN2395, TNF-α, or LPS.Secreted cytokines were quantified by multiplex immunoassay, and contractility was assessed by an in-gel cell contraction assay (n = 9). Induction of hTERT-HM contractility was also evaluated indirectly following exposure to conditioned media from primary term decidual cells (n = 4) previously stimulated with ODN2395.Results: Toll-like receptor 9 immunostaining in placenta and amniochorion was strongest in decidual cells, but unrelated to labor. TLR9 staining intensity was significantly decreased in TL compared with TNL myometrium (P = 0.002). Although total cfDNA in maternal circulation increased in TL (P = 0.025 vs TNL), difference in cffDNA was non-significant. Myometrial TLR9 mRNA levels were unaffected by contractile status and far less abundant than other pro-inflammatory TLRs. hTERT-HM contractility was enhanced by LPS (P = 0.002) and TNF-α (P = 0.003), but not by ODN2395 (P = 0.345) or supernatant of TLR9-stimulated decidual cells.Conclusion: Myometrial and decidual TLR9 are unlikely to directly regulate human parturition. K E Y W O R D Scytokines, decidua, DNA, labor, myometrium, toll-like receptor 9

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Section: Discussionsupporting

confidence: 84%

Toll‐like receptor 9, maternal cell‐free DNA and myometrial cell response to CpG oligodeoxynucleotide stimulation

Beck

Buhimschi

Summerfield

et al. 2019

American J Rep Immunol

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“…Oxytocin is also important in the process of parturition (Table 6 ; Oxytocin); it stimulates the contraction of smooth muscle cells in the myometrium (Ayar et al, 2001 ; Arrowsmith and Wray, 2014 ), by inducing calcium influx and stimulating prostaglandin release (Wilson et al, 1988 ; Voltolini and Petraglia, 2014 ; Kim S. H. et al, 2017 ). Cardiovascular effects of oxytocin include its ability to significantly lower blood pressure in non-pregnant rats (Petersson et al, 1996 ).…”

Section: Placental Hormones That Mediate Maternal Adaptations To Pregmentioning

confidence: 99%

The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation

et al. 2018

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During pregnancy, the mother must adapt her body systems to support nutrient and oxygen supply for growth of the baby in utero and during the subsequent lactation. These include changes in the cardiovascular, pulmonary, immune and metabolic systems of the mother. Failure to appropriately adjust maternal physiology to the pregnant state may result in pregnancy complications, including gestational diabetes and abnormal birth weight, which can further lead to a range of medically significant complications for the mother and baby. The placenta, which forms the functional interface separating the maternal and fetal circulations, is important for mediating adaptations in maternal physiology. It secretes a plethora of hormones into the maternal circulation which modulate her physiology and transfers the oxygen and nutrients available to the fetus for growth. Among these placental hormones, the prolactin-growth hormone family, steroids and neuropeptides play critical roles in driving maternal physiological adaptations during pregnancy. This review examines the changes that occur in maternal physiology in response to pregnancy and the significance of placental hormone production in mediating such changes.

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“…Interestingly, the genes affected by SV in GZP enriched in several mainly pathway related to reproduction, immune and adaptability, containing oxytocin signaling pathway, mTOR signaling pathway, axon guidance and cholinergic synapse. This oxytocin signaling pathway has a role in uterine contractions during parturition and milk release during lactation [ 64 ]. The mTOR signaling pathway regulated in porcine reproductive and respiratory syndrome virus (PRRSV) infected porcine alveolar macrophages at different activation statuses [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Detection of genomic structural variations in Guizhou indigenous pigs and the comparison with other breeds

et al. 2018

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Genomic structural variation (SV) is noticed for the contribution to genetic diversity and phenotypic changes. Guizhou indigenous pig (GZP) has been raised for hundreds of years with many special characteristics. The present paper aimed to uncover the influence of SV on gene polymorphism and the genetic mechanisms of phenotypic traits for GZP. Eighteen GZPs were chosen for resequencing by Illumina sequencing platform. The confident SVs of GZP were called out by both programs of pindel and softSV simultaneously and compared with the SVs deduced from the genomic data of European pig (EUP) and the native pig outside of Guizhou, China (NPOG). A total of 39,166 SVs were detected and covered 27.37 Mb of pig genome. All of 76 SVs were confirmed in GZP pig population by PCR method. The SVs numbers in NPOG and GZP were about 1.8 to 1.9 times higher than that in EUP. And a SV hotspot was found out from the 20 Mb of chromosome X of GZP, which harbored 29 genes and focused on histone modification. More than half of SVs was positioned in the intergenic regions and about one third of SVs in the introns of genes. And we found that SVs tended to locate in genes produced multi-transcripts, in which a positive correlation was found out between the numbers of SV and the gene transcripts. It illustrated that the primary mode of SVs might function on the regulation of gene expression or the transcripts splicing process. A total of 1,628 protein-coding genes were disturbed by 1,956 SVs specific in GZP, in which 93 GZP-specific SV-related genes would lose their functions due to the SV interference and gathered in reproduction ability. Interestingly, the 1,628 protein-coding genes were mainly enriched in estrogen receptor binding, steroid hormone receptor binding, retinoic acid receptor binding, oxytocin signaling pathway, mTOR signaling pathway, axon guidance and cholinergic synapse pathways. It suggested that SV might be a reason for the strong adaptability and low fecundity of GZP, and 51 candidate genes would be useful for the configuration phenotype in Xiang pig breed.

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Advances in the role of oxytocin receptors in human parturition

Cited by 50 publications

References 95 publications

Toll‐like receptor 9, maternal cell‐free DNA and myometrial cell response to CpG oligodeoxynucleotide stimulation

Toll‐like receptor 9, maternal cell‐free DNA and myometrial cell response to CpG oligodeoxynucleotide stimulation

The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation

Detection of genomic structural variations in Guizhou indigenous pigs and the comparison with other breeds

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