Effect of cytochrome <scp>P</scp>‐450 epoxygenase and hydroxylase metabolites on rat myometrium contractility in non‐pregnancy, late pregnancy and late pregnancy under inflammatory conditions

Corriveau, Stéphanie; Berthiaume, Maryse; Girard, Isabelle; Nolin, Marc-Antoine; Rousseau, Éric; Pasquier, Jean-Charles

doi:10.1111/jog.12247

Cited by 6 publications

(8 citation statements)

References 32 publications

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“…Of note, inflammatory conditions induced an increase in the amplitude, the time to peak and the duration of phasic contractions, corroborating previous works [29,28] by Ross et al in which the authors demonstrated an increase in amplitude of spontaneous rhythmic contractions in their LPStreated group [31]. Note that the frequency of contractions under LPS was decreased unexpectedly and could be explained by the major increase in amplitude and duration of the phasic contractions.…”

Section: Contractile Activitysupporting

confidence: 89%

“…Myometrial rings (n = 72) were obtained by median laparatomy at G22 from Sprague-Dawley rats as previously described [28]. Each uterine horn was dissected in 6 uterine rings.…”

Section: Tissue Collection and Isometric Tension Measurementsmentioning

confidence: 99%

“…For each sample, 1 stirrup was fixed to the bottom of the chamber, and the other was connected to an isometric force transducer coupled to Polyview software (Grass-Astro-Med Inc., West Warwick, RI). The organ baths (Radnoti Glass Tech., Monrovia, CA) contained 7 ml of Krebs solution thermostated at 37 C and bubbled continuously with carbogen (95% O 2 -5% CO 2 ; pH 7.40) as previously described [28].…”

Section: Tissue Collection and Isometric Tension Measurementsmentioning

confidence: 99%

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Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Corriveau

Blouin

Burt

et al. 2016

European Journal of Obstetrics & Gynecology and Reproductiv

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Section: Contractile Activitysupporting

confidence: 89%

“…Myometrial rings (n = 72) were obtained by median laparatomy at G22 from Sprague-Dawley rats as previously described [28]. Each uterine horn was dissected in 6 uterine rings.…”

Section: Tissue Collection and Isometric Tension Measurementsmentioning

confidence: 99%

Section: Tissue Collection and Isometric Tension Measurementsmentioning

confidence: 99%

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Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Corriveau

Blouin

Burt

et al. 2016

European Journal of Obstetrics & Gynecology and Reproductiv

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“…Similarly, eicosanoids produced through CYP450 pathway also contribute to vascular remodeling, with a hypothesized link to hypertension and inflammation 34 . For instance, in rat models, disruption in the production of eicosanoids from the CYP450 pathway has been shown to alter myometrium contractile activity 35 and lead to the development of hypertension and renal dysfunction 36 . Thus, LOX and CYP450 eicosanoid products as whole groups can be useful in predicting broad pathological precursors to preterm birth; whereas analysis of disruption in any single metabolite may only provide limited insight due to potential compensatory roles of multiple metabolites produced from the same pathway.…”

Section: Discussionmentioning

confidence: 99%

Prediction and associations of preterm birth and its subtypes with eicosanoid enzymatic pathways and inflammatory markers

Aung

Ferguson

et al. 2019

Sci Rep

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Endogenous signaling molecules derived from lipids, peptides, and DNA, are important regulators of physiological processes during pregnancy. The effect of their collective impact on preterm birth (delivery < 37 weeks gestation) is understudied. We aimed to characterize the associations and predictive capacity of an extensive panel of eicosanoids, immune biomarkers, oxidative stress markers, and growth factors towards preterm birth and its subtypes. We conducted a cross-sectional study of pregnant women (recruited < 15 weeks gestation) in the LIFECODES birth cohort, which included 58 cases of preterm birth and 115 controls that delivered term. Among the cases there were 31 cases who had a spontaneous preterm birth (cases who had spontaneous preterm labor and/or preterm premature rupture of membranes) and 25 that had preterm birth associated with aberrant placentation (cases who had preeclampsia and/or intrauterine growth restriction) and 2 cases that could not be sufficiently categorized as either. We analyzed single biomarker associations with each preterm birth outcome using multiple logistic regression. Adaptive elastic-net was implemented to perform a penalized multiple logistic regression on all biomarkers simultaneously to identify the most predictive biomarkers. We then organized biomarkers into biological groups and by enzymatic pathways and applied adaptive elastic-net and random forest to evaluate the accuracy of each group for predicting preterm birth cases. The majority of associations we observed were for spontaneous preterm birth, and adaptive elastic-net identified 5-oxoeicosatetraenoic acid, resolvin D1, 5,6-epoxy-eicsatrienoic acid, and 15-deoxy-12,14-prostaglandin J2 as most predictive. Overall, lipid biomarkers performed the best at separating cases from controls compared to other biomarker categories (adaptive elastic-net AUC = 0.78 [0.62, 0.94], random forest AUC = 0.84 [0.72, 0.96]). Among the enzymatic pathways that differentiate eicosanoid metabolites, we observed the highest prediction of overall preterm birth by lipoxygenase metabolites using random forest (AUC = 0.83 [0.69, 0.96]), followed by cytochrome p450 metabolites using adaptive elastic-net (AUC = 0.74 [0.52, 0.96]). In this study we translate biological hypothesis into the language of modern machine learning. Many lipid biomarkers were highly associated with overall and spontaneous preterm birth. Among eicosanoids, lipoxygenase and cytochrome p450 products performed best in identifying overall and spontaneous preterm birth. The combination of lipid biomarkers may have good utility in clinical settings to predict preterm birth.

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“…For each tissue, 1 stirrup was fixed to the bottom of the chamber, and the other was connected to an isometric force transducer coupled to Polyview software (Grass-Astro-Med Inc, West Warwick, RI). The organ chambers contained 7 ml of Krebs solution maintained at 37 °C and continuously bubbled with a mixture of 95% oxygen/5% carbon dioxide (pH 7.40) as previously described [14] . After a 1 h equilibration period, spontaneous contractile activity was recorded after which tested agents were sequentially added.…”

Section: Methodsmentioning

confidence: 99%

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model

Corriveau

Blouin

Raiche

et al. 2015

Journal of Clinical & Translational Endocrinology

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ObjectiveAbnormal uterine contraction patterns were recently demonstrated in uterine strips from pregnant women treated with Levothyroxine (T4). These abnormalities were correlated with an increased risk of C-section delivery and associated surgical complications. To date, no study has investigated whether uterine contractility is modified by hypothyroidism or T4 treatment. Herein, we analyze the physiological role of T4 on uterine contractions.Study designFemale non-pregnant Sprague–Dawley rats (N = 22) were used and divided into four groups: 1) control, 2) hypothyroidism, 3) hypothyroidism treated with low T4 doses (20 μg/kg/day) and 4) with high T4 doses (100 μg/kg/day). Hypothyroidism was induced by an iodine-deficient diet. Isometric tension measurements were performed in vitro on myometrium tissues in isolated organ baths. Contractile activity parameters were quantified (amplitude, duration, frequency and area under the curve) using pharmacological tools to assess their effect.ResultsScreening of thyroid function confirmed a hypothyroid state for all rats under iodine-free diet to which T4 was subsequently administered to counterbalance hypothyroidism. Results demonstrate that hypothyroidism significantly decreased contractile duration (−17%) and increased contractile frequency (+26%), while high doses of T4 increased duration (+200%) and decreased frequency (−51%). These results thus mimic the pattern of abnormal contractions previously observed in uterine tissue from T4-treated hypothyroid pregnant women.ConclusionOur data suggest that changes in myometrial reactivity are induced by T4 treatment. Thus, in conjunction with our previous observations on human myometrial strips, management of hypothyroidism should be improved to reduce the rate of C-sections in this group of patients.

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Effect of cytochrome P‐450 epoxygenase and hydroxylase metabolites on rat myometrium contractility in non‐pregnancy, late pregnancy and late pregnancy under inflammatory conditions

Cited by 6 publications

References 32 publications

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model

Prediction and associations of preterm birth and its subtypes with eicosanoid enzymatic pathways and inflammatory markers

Levothyroxine treatment generates an abnormal uterine contractility patterns in an in vitro animal model

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