Metabolic mechanisms of uterine contractility in labor
临产时子宫收缩力的代谢机制
基本信息
- 批准号:10741953
- 负责人:
- 金额:$ 42.76万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-05 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:Adipose tissueAffectAgeAgonistAtopobium vaginaeAutomobile DrivingBehavior TherapyBirthBody mass indexCell SeparationCervicalCesarean sectionContractsDataDefectDiseaseDoseEnergy MetabolismEuropeExerciseFailureFatty AcidsFetusFiberFrequenciesFunctional disorderGene ExpressionGlucoseGlucose TransporterGlycolysisGoalsHourHumanInfantKnowledgeLabor DystociaLipidsLuteolysisMetabolicMetabolic PathwayMusMuscleMyocardiumMyometrialObese MiceObesityOutcomeOxytocinPatternPhenotypePractice ManagementPregnancyPrevalenceProgesteroneProstaglandinsResearchResolutionRiskRisk FactorsSkeletal MuscleSmooth MuscleSmooth Muscle MyocytesSpirometryTelemetryTestingThinnessTriglyceridesTrimetazidineUterine ContractionUterusVaginal delivery procedureWeightWithdrawalWomanWorkdiet-induced obesityetomoxirevidence baseglucose uptakeimprovedin vivoinhibitorinsulin sensitivitymaternal morbiditymaternal obesitymaternal outcomematernal riskmother nutritionmouse modelmyometriumneonatal morbidityneonatal outcomeobstetric outcomesobstetrical complicationoxidationpharmacologicpreferencepupreproductiveresponseuptakeuterine contractility
项目摘要
PROJECT SUMMARY/ABSTRACT
Maternal obesity is associated with lower rates of spontaneous labor, slower progress of cervical dilation,
and increased risks of labor arrest disorders and induction failure. Additionally, compared to lean women,
women with obesity have a nearly three-fold higher rate of cesarean delivery, putting them at increased risk
of maternal and neonatal morbidity. While the association between maternal obesity and abnormal labor has
been well documented, the mechanisms responsible for this remain unknown. Evidence suggests that
obesity causes uterine contractility dysfunction in women. Uterine smooth muscle (myometrium) from women
with obesity contracts with less force and frequency than myometrium from normal-weight women and
women with obesity require higher doses of oxytocin to achieve a vaginal delivery, suggesting abnormal
contractile response. We developed a mouse model of diet-induced obesity that recapitulates the
dysfunctional labor patterns seen in women with obesity and can be applied for further mechanistic studies.
Here, our objective is to provide a mechanistic understanding of myometrial energy metabolism in control
and obese mice during parturition. We focus on energy metabolism because the contractility required for
cervical dilation and expulsion of the fetus during labor – lasting for hours to days in humans – places a high
energy demand on the myometrium. Our preliminary data also suggest that obese dams have significantly
higher lipid (triglyceride and fatty acids) content, increased expression of genes responsible for fatty acid
uptake and storage, dysfunctional glycolytic flux, and decreased expression of a key glucose transporter in
the myometrium than control dams at term. Thus, our overall hypothesis is that excess fatty acid and
triglycerides in the myometrium of obese dams inhibit glucose oxidation, which is required for initiation and
progression of early labor. Despite the fact that millions of women deliver an infant each year, we know
surprisingly little about how the myometrium meets its energy demands in healthy women or those with
obesity. The goals of this project are to (1) define the effects of diet-induced obesity on spontaneous and
agonist-induced myometrial contractility and parturition in mice and (2) determine the effects of myometrial
energy substrate availability on uterine contractility during labor in the mouse. Our proposed research will
provide the necessary mechanistic data to develop pharmacologic and behavioral interventions to optimize
myometrial energy storage and utilization during labor. Ultimately, this research may allow us to improve
obstetric outcomes for millions of women with obesity.
项目总结/摘要
母亲肥胖与自然分娩率较低,宫颈扩张进展缓慢,
以及增加分娩停滞障碍和引产失败的风险。此外,与瘦女性相比,
肥胖妇女的剖腹产率高出近三倍,使她们面临更大的风险。
产妇和新生儿的发病率。虽然母亲肥胖和异常分娩之间的联系
尽管有大量文献记载,但造成这种情况的机制仍然不明。证据表明
肥胖导致女性子宫收缩功能障碍。来自女性的子宫平滑肌(子宫肌层)
与正常体重的妇女相比,肥胖妇女子宫肌层收缩的力量和频率更小,
肥胖的女性需要更高剂量的催产素才能实现阴道分娩,这表明
收缩反应我们开发了一种饮食诱导肥胖的小鼠模型,
在肥胖妇女中观察到的功能失调的分娩模式,可以应用于进一步的机制研究。
在这里,我们的目标是提供一个机制的理解,子宫肌层能量代谢控制
和肥胖的小鼠。我们专注于能量代谢,因为
子宫颈扩张和胎儿在分娩过程中的排出--人类持续数小时至数天--使高血压发生在子宫颈。
子宫肌层的能量需求。我们的初步数据还表明,肥胖的母鼠
脂质(甘油三酯和脂肪酸)含量较高,负责脂肪酸的基因表达增加
摄取和储存,功能失调的糖酵解通量,和减少表达的关键葡萄糖转运蛋白,
子宫肌层比对照组母鼠在足月。因此,我们的总体假设是,过量的脂肪酸和
肥胖母鼠子宫肌层中的甘油三酸酯抑制葡萄糖氧化,葡萄糖氧化是启动和
早期劳动的进展。尽管每年有数百万妇女分娩,
令人惊讶的是,关于子宫肌层如何满足健康女性或患有
肥胖本项目的目标是(1)确定饮食诱导的肥胖对自发性和
激动剂诱导的小鼠子宫肌层收缩性和分娩,以及(2)确定子宫肌层收缩性和分娩的影响。
能量底物利用率对小鼠分娩期间子宫收缩力的影响。我们的研究计划将
提供必要的机制数据,以开发药理学和行为干预措施,
产程中子宫肌层的能量储存和利用。最终,这项研究可能会让我们改善
数百万肥胖妇女的产科结局。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Antonina I Frolova其他文献
Antonina I Frolova的其他文献
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{{ truncateString('Antonina I Frolova', 18)}}的其他基金
Steroid regulation of glucose utilization during early pregnancy.
妊娠早期葡萄糖利用的类固醇调节。
- 批准号:
7612302 - 财政年份:2008
- 资助金额:
$ 42.76万 - 项目类别:
Steroid regulation of glucose utilization during early pregnancy.
妊娠早期葡萄糖利用的类固醇调节。
- 批准号:
7741207 - 财政年份:2008
- 资助金额:
$ 42.76万 - 项目类别:
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