Effects of leptin on lipopolysaccharide-induced myometrial apoptosis in an in vitro human model of chorioamnionitis

Wendremaire, Maëva; Bardou, Marc; Peyronel, Caroline; Hadi, Tarik; Sagot, Paul; Lirussi, Frédéric

doi:10.1016/j.ajog.2011.05.041

Cited by 17 publications

(21 citation statements)

References 46 publications

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“…However, STAT3 activation in this cell type remains primordial as it induces the expression of the anti‐apoptotic protein Bcl2 and protects the cell against death. Consistent with this, our team has demonstrated anti‐apoptotic effects of leptin in the myometrium (Wendremaire et al ., ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in vitro studies have shown that leptin is able to oppose both spontaneous and oxytocin‐induced contractions in human myometrium (Moynihan et al ., ). It also prevents myometrial cell apoptosis and extracellular matrix remodelling (Wendremaire et al ., 2011; 2013), two common features of uterine preparation for labour (Smith, ), in an in vitro model of human myometrial inflammation. Another common feature of labour onset is the switch in the phenotype of myometrial smooth muscle cells from a proliferative to a hypertrophic state, which allows the synthesis of contractile material (Sharma et al ., ; Magarinos et al ., ; Saxena et al ., ; Tanfin et al ., ).…”

Section: Introductionmentioning

confidence: 99%

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Dose‐dependent biphasic leptin‐induced proliferation is caused by non‐specific IL‐6/NF‐κB pathway activation in human myometrial cells

Barrichon

Hadi

Wendremaire

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSELeptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour (PTL), as it is able to prevent in vitro uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence. EXPERIMENTAL APPROACHWe stimulated human primary myometrial smooth muscle cells with leptin in the presence or absence of receptor antagonists or signalling pathway inhibitors. KEY RESULTSLeptin induced myometrial cell proliferation in a biphasic manner. At 6.25 ng·mL , leptin induced direct non-specific stimulation of the IL-6 receptor, leading to NF-κB activation, and exerted anti-proliferative effects. However, at 50 ng·mL, leptin re-induces proliferation via IL-6 receptor stimulation that requires STAT3 and delayed ERK1/2 activation. CONCLUSIONS AND IMPLICATIONSThese data bring new insights into leptin signalling-induced myometrial proliferation and its interrelationship with the IL-6/IL-6 receptor axis. In the light of our previous work, the present study emphasizes the potential value of leptin in the pharmacological management of PTL and it also strengthens the hypothesis that leptin might be a contributory factor in the parturition-related disorders observed in obese women.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dose‐dependent biphasic leptin‐induced proliferation is caused by non‐specific IL‐6/NF‐κB pathway activation in human myometrial cells

Barrichon

Hadi

Wendremaire

et al. 2015

British J Pharmacology

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“…17 However, actin signals did not decrease in high BMI patients, which may also be attributed to high leptin levels that have been shown to prevent cell apoptosis in vitro. 14,64 …”

Section: Commentmentioning

confidence: 99%

In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy

O’Brien

Vargis

Rudin

et al. 2018

American Journal of Obstetrics and Gynecology

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BACKGROUND The cervix must undergo significant biochemical remodeling to allow for successful parturition. This process is not fully understood, especially in instances of spontaneous preterm birth. In vivo Raman spectroscopy is an optical technique that can be used to investigate the biochemical composition of tissue longitudinally and non-invasively in human beings, and has been utilized to measure physiology and disease states in a variety of medical applications. OBJECTIVE The purpose of this study is to measure in vivo Raman spectra of the cervix throughout pregnancy in women, and to identify biochemical markers that change with the preparation for delivery and postpartum repair. STUDY DESIGN In all, 68 healthy pregnant women were recruited. Raman spectra were measured from the cervix of each patient monthly in the first and second trimesters, weekly in the third trimester, and at the 6-week postpartum visit. Raman spectra were measured using an in vivo Raman system with an optical fiber probe to excite the tissue with 785 nm light. A spectral model was developed to highlight spectral regions that undergo the most changes throughout pregnancy, which were subsequently used for identifying Raman peaks for further analysis. These peaks were analyzed longitudinally to determine if they underwent significant changes over the course of pregnancy (P < .05). Finally, 6 individual components that comprise key biochemical constituents of the human cervix were measured to extract their contributions in spectral changes throughout pregnancy using a linear combination method. Patient factors including body mass index and parity were included as variables in these analyses. RESULTS Raman peaks indicative of extracellular matrix proteins (1248 and 1254 cm−1) significantly decreased (P < .05), while peaks corresponding to blood (1233 and 1563 cm−1) significantly increased (P <.0005) in a linear manner throughout pregnancy. In the postpartum cervix, significant increases in peaks corresponding to actin (1003, 1339, and 1657 cm−1) and cholesterol (1447 cm−1) were observed when compared to late gestation, while signatures from blood significantly decreased. Postpartum actin signals were significantly higher than early pregnancy, whereas extracellular matrix proteins and water signals were significantly lower than early weeks of gestation. Parity had a significant effect on blood and extracellular matrix protein signals, with nulliparous patients having significant increases in blood signals throughout pregnancy, and higher extracellular matrix protein signals in early pregnancy compared to patients with prior pregnancies. Body mass index significantly affected actin signal contribution, with low body mass index patients showing decreasing actin contribution throughout pregnancy and high body mass index patients demonstrating increasing actin signals. CONCLUSION Raman spectroscopy was successfully used to biochemically monitor cervical remodeling in pregnant women during pre-natal visits. This foundational study has d...

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“…Some researchers also found that hormones can regulate the apoptosis, and through this way hormone can control the metabolism of tissues or organs. For example, the leptin is one hormone produced by adipocytes, and it has been found as a inhibitor of apoptosis, leptin can down-regulate cleaved caspase-3 and Bcl-2 associated X protein and up-regulate Bcl-2 protein, if this hormone level is normal, there will be no apoptosis, however, if the hormone level decreased, the apoptosis will happen [27], this is one mechanism by which the hormone act as inhibitor of apoptosis, the other mechanism is that hormone act as an inducer of apoptosis. The majority relations between the hormone and apoptosis are concluded as below the …”

Section: Hormonementioning

confidence: 99%

Extrinsic and Intrinsic Apoptosis Signal Pathway Review

Hongmei¹

2012

Apoptosis and Medicine

106

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Effects of leptin on lipopolysaccharide-induced myometrial apoptosis in an in vitro human model of chorioamnionitis

Cited by 17 publications

References 46 publications

Dose‐dependent biphasic leptin‐induced proliferation is caused by non‐specific IL‐6/NF‐κB pathway activation in human myometrial cells

Dose‐dependent biphasic leptin‐induced proliferation is caused by non‐specific IL‐6/NF‐κB pathway activation in human myometrial cells

In vivo Raman spectroscopy for biochemical monitoring of the human cervix throughout pregnancy

Extrinsic and Intrinsic Apoptosis Signal Pathway Review

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