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.
项目概要/摘要
产妇肥胖与自然分娩率较低、宫颈扩张进展缓慢、
产程逮捕障碍和引产失败的风险增加。另外,与瘦女性相比,
肥胖女性的剖腹产率高出近三倍,使她们面临更高的风险
孕产妇和新生儿发病率。虽然孕产妇肥胖与异常分娩之间存在关联
虽然已有详细记录,但造成这种现象的机制仍然未知。有证据表明
肥胖会导致女性子宫收缩功能障碍。女性子宫平滑肌(子宫肌层)
与正常体重女性相比,肥胖女性的子宫肌层收缩力和频率更小,
肥胖女性需要更高剂量的催产素才能实现阴道分娩,这表明存在异常
收缩反应。我们开发了饮食诱发肥胖的小鼠模型,该模型概括了
肥胖女性中观察到的功能失调的分娩模式可用于进一步的机制研究。
在这里,我们的目标是提供对控制子宫肌层能量代谢的机制理解
和分娩期间的肥胖小鼠。我们关注能量代谢,因为能量代谢所需的收缩性
分娩过程中宫颈扩张和胎儿排出——在人类中持续数小时至数天——使
子宫肌层的能量需求。我们的初步数据还表明,肥胖的水坝有显着的
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、糖酵解通量功能失调以及关键葡萄糖转运蛋白的表达减少
足月子宫肌层高于对照母鼠。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酯抑制葡萄糖氧化,这是启动和
早期临产的进展。尽管每年有数百万妇女分娩,但我们知道
令人惊讶的是,关于健康女性或患有子宫肌瘤的女性的子宫肌层如何满足其能量需求却知之甚少。
肥胖。该项目的目标是 (1) 定义饮食引起的肥胖对自发性肥胖和肥胖的影响。
激动剂诱导的小鼠子宫肌层收缩性和分娩,以及(2)确定子宫肌层的影响
小鼠分娩过程中能量底物可用性对子宫收缩力的影响。我们提出的研究将
提供必要的机制数据来开发药理学和行为干预措施以优化
分娩过程中子宫肌层能量的储存和利用。最终,这项研究可能会让我们改进
数百万肥胖女性的产科结果。
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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