Reduced Expression of Hydrogen Sulfide–Generating Enzymes Down-Regulates 15-Hydroxyprostaglandin Dehydrogenase in Chorion during Term and Preterm Labor

Sun, Qianqian; Chen, Zixi; He, Ping; Li, Yuan; Ding, Xiaoying; Huang, Ying; Gu, Hang; Ni, Xin

doi:10.1016/j.ajpath.2017.09.006

Cited by 12 publications

(9 citation statements)

References 32 publications

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“…CBS is more abundant in rats [303]. CBS and CSE expression is lower in TL membranes compared with TNL cesarean controls [304]. Since sulfide attenuates oxidative stress and inhibits prostaglandin synthesis, CBS expression might reduce inflammation and delay membrane rupture [305].…”

Section: Rupture Of Membranesmentioning

confidence: 99%

Gasotransmitters in pregnancy: from conception to uterine involution†

Guerra

Hurt

2019

Biology of Reproduction

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Gasotransmitters are endogenous small gaseous messengers exemplified by nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S or sulfide). Gasotransmitters are implicated in myriad physiologic functions including many aspects of reproduction. Our objective was to comprehensively review basic mechanisms and functions of gasotransmitters during pregnancy from conception to uterine involution and highlight future research opportunities. We searched PubMed and Web of Science databases using combinations of keywords nitric oxide, carbon monoxide, sulfide, placenta, uterus, labor, and pregnancy. We included English language publications on human and animal studies from any date through August 2018 and retained basic and translational articles with relevant original findings. All gasotransmitters activate cGMP signaling. NO and sulfide also covalently modify target protein cysteines. Protein kinases and ion channels transduce gasotransmitter signals, and co-expressed gasotransmitters can be synergistic or antagonistic depending on cell type. Gasotransmitters influence tubal transit, placentation, cervical remodeling, and myometrial contractility. NO, CO, and sulfide dilate resistance vessels, suppress inflammation, and relax myometrium to promote uterine quiescence and normal placentation. Cervical remodeling and rupture of fetal membranes coincide with enhanced oxidation and altered gasotransmitter metabolism. Mechanisms mediating cellular and organismal changes in pregnancy due to gasotransmitters are largely unknown. Altered gasotransmitter signaling has been reported for preeclampsia, intrauterine growth restriction, premature rupture of membranes, and preterm labor. However, in most cases specific molecular changes are not yet characterized. Nonclassical signaling pathways and the crosstalk among gasotransmitters are emerging investigation topics.

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Section: Rupture Of Membranesmentioning

confidence: 99%

Gasotransmitters in pregnancy: from conception to uterine involution†

Guerra

Hurt

2019

Biology of Reproduction

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“…Our previous study demonstrated that human placenta samples express H 2 S synthetase, CSE and CBS, and deficiency of CSE and CBS in the placenta is associated with preeclampsia ( 32 ). Previous studies have also reported that deficiency in H 2 S synthetase is associated with other pregnancy complications, including premature labor ( 33 ) and fetal growth restriction ( 34 ). Thus, H 2 S may participate in the pathogenesis of GDM by regulating activation of the NLPR3 inflammasome in placentas.…”

Section: Introductionmentioning

confidence: 99%

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Tan

et al. 2021

Exp Ther Med

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The placenta may play a key role in the activation of inflammation and initiation of insulin resistance (IR) during gestational diabetes mellitus (GDM) pathogenesis. Interleukin (IL)-1β and IL-18, regulated by NLR family pyrin domain containing-3 (NLRP3) inflammasome, are important inflammatory cytokines in the initiation of maternal IR during GDM. However, the mechanism responsible for the regulatory of NLRP3 inflammasome in placenta remains unknown. Hydrogen sulfide (H 2 S) exerts anti-inflammatory function partially via suppressing the activation of the NLPR3 inflammasome. The present study aimed to investigate the role of NLRP3 inflammasome, H 2 S synthetase cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) in placenta in the pathogenesis of GDM. Clinical placenta samples were collected from pregnant women with GDM (n=16) and healthy pregnant women at term (n=16). Western blot analysis was performed to detect the protein expression levels of NLRP3, cleaved caspase-1, CBS and CSE in the placenta samples. Pearson's correlation analysis was performed to assess the correlation between NLRP3 inflammasome and H 2 S synthetase. Human placental cells were cultured and treated with different concentrations of NaHS (0, 10, 25 and 50 nmol/l) or L-cysteine (0, 0.25, 0.50 and 1.00 mmol/l). In addition, western blot analysis was performed to detect the protein expression levels of NLRP3 and cleaved caspase-1, while ELISA was performed to measure the production of IL-1β and IL-18 in the culture media. The results demonstrated that the expression levels of NLRP3 and cleaved caspase-1 increased, while the expression levels of CBS and CSE decreased in the placenta samples. In addition, the expression levels of NLRP3 and cleaved caspase-1 were inversely correlated with the expression levels of CBS and CSE. Notably, NaHS and L-cysteine significantly suppressed the expression levels of NLRP3 and cleaved caspase-1, and the production of IL-1 and IL-18 in human placental cells. Taken together, the results of the present study suggest that H 2 S synthetase deficiency in placenta may contribute to excessive activation of NLRP3 inflammasome in GDM.

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“… 25 , 26 Our previous study found that the expression levels of the H 2 S-generating enzymes CBS and CSE and the production of H 2 S are decreased with the onset of labour and preterm labour in human chorionic tissues and the myometrium. 27 , 28 Furthermore, our studies have demonstrated that H 2 S produced by CSE and CBS contributes to uterine quiescence during pregnancy, 28 which suggests that H 2 S is involved in the initiation of labour. However, the mechanism by which H 2 S contributes to uterine quiescence and the regulation of labour remains largely unknown.…”

Section: Introductionmentioning

confidence: 77%

Hydrogen Sulfide Contributes to Uterine Quiescence Through Inhibition of NLRP3 Inflammasome Activation by Suppressing the TLR4/NF-κB Signalling Pathway

Chen¹,

Zhang²,

Zhao³

et al. 2021

JIR

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Background The NLRP3 inflammasome plays a critical role in inflammatory responses in various diseases. Our previous study showed that NLRP3 expression was significantly increased in human pregnancy tissue during term labour. Therefore, we explored whether NLRP3 participated in inflammatory responses of preterm and term labour and whether this process could be relieved by H 2 S, one anti-inﬂammatory gasotransmitter. Methods Human myometrium was obtained from non-labouring and labouring women. Mouse myometrium was obtained from LPS-induced infectious preterm labour. Uterine smooth muscle cells were isolated from non-labouring women’s myometrial tissues, transfected with siRNA, and treated cells with IL-1β, H 2 S donor NaHS, NF-κB inhibitor BAY 11–7082 and TLR4 inhibitorTAK-242. The NLRP3 inflammasome, CSE, CBS, TLR4, uterine contraction-associated proteins (CAPs), NF-κB activation and inflammatory cytokine expression were assessed by Western blotting and RT-PCR. Results The NLRP3 inflammasome, TLR4 and activated NF-κB expression were upregulated in human term labour, mouse preterm labour and human uterine smooth muscle cells treated with IL-1β. NLRP3 levels were negatively correlated with CSE and CBS expression. Treatment with the H 2 S donor NaHS delayed LPS-induced preterm birth in mice and inhibited NLRP3 inflammasome activation. In siNLRP3-transfected cells, there was a significant decrease in the expression of CAPs and inflammatory cytokines compared with IL-1β stimulation. In addition, treatment with the H 2 S donor NaHS inhibited NLRP3 inflammasome activation, reduced the expression of uterine contraction-associated proteins and inflammatory cytokines and reduced the activation of TLR4 and NF-κB compared with stimulation with IL-1β in human uterine smooth muscle cells. Furthermore, treatment of uterine smooth muscle cells with BAY 11–7082 and TAK-242 found that NLRP3 activation was regulated by the TLR4 and NF-κB pathways. Conclusion H 2 S suppresses CAP expression and the inflammatory response and contributes to uterine quiescence by inhibiting the TLR4/NF-κB signalling pathway and downstream NLRP3 inflammasome activation. Thus, H 2 S contributes to uterine quiescence through inhibition of NLRP3 inflammasome activation by suppressing the TLR4/NF-κB signalling pathway.

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Reduced Expression of Hydrogen Sulfide–Generating Enzymes Down-Regulates 15-Hydroxyprostaglandin Dehydrogenase in Chorion during Term and Preterm Labor

Cited by 12 publications

References 32 publications

Gasotransmitters in pregnancy: from conception to uterine involution†

Gasotransmitters in pregnancy: from conception to uterine involution†

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency

Hydrogen Sulfide Contributes to Uterine Quiescence Through Inhibition of NLRP3 Inflammasome Activation by Suppressing the TLR4/NF-κB Signalling Pathway

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