Epithelial Regeneration in the Adult Oviduct
成人输卵管上皮再生
基本信息
- 批准号:10542901
- 负责人:
- 金额:$ 3.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-01 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectApicalApoptosisBypassCell DeathCell ShapeCellsCellular biologyCenters for Disease Control and Prevention (U.S.)CiliaCollaborationsCore-Binding FactorDevelopmentEctopic PregnancyEmbryoEpithelialEstrogensEstrous CycleEventFemaleFemale infertilityFertilityFertility DisordersFertilizationFertilization in VitroGenesGeneticGenetic TranscriptionGenomicsGoalsHomeostasisHormonalHormonal ChangeHumanImageInfertilityLabelMammalian OviductsMammalsMedicineModelingMolecularMolecular BiologyMolecular GeneticsMorphogenesisMusMutant Strains MiceNatural regenerationOocytesOptical Coherence TomographyOrganOvaryOvulationPathologyPeriodicityPhysiologyPopulationPregnancy RatePrevalenceProgesteroneProteinsPseudostratified EpitheliumRecurrenceReporterRoleSecretory CellSiteSurfaceTherapeuticTimeTissuesTransgenic MiceTransgenic OrganismsTravelUnited StatesUterusWomanWomen&aposs HealthWorkapical membranecell behaviorcilium motilitycollegeendometriosisepithelium regenerationfemale fertilityfluid flowhigh resolution imagingimprovedin vivoin vivo imaginginsightloss of functionmouse geneticsmouse modelmutantnovelplanar cell polaritypregnantreproductivereproductive organresponsestem cell populationstem cellssuccesstranscriptometranscriptome sequencing
项目摘要
Project Summary
Despite the prevalence of female reproductive pathologies, such as endometriosis and ectopic pregnancy, there
is shockingly little known about the molecular or cell biology of the organs involved. This proposal focuses on
the oviduct, because the oviduct serves as the conduit between the ovary and uterus, and is the site of
mammalian fertilization. While the oviduct is a critical site for female fertility, how oviduct physiology is regulated
at the genetic, molecular, and cellular level is almost completely unknown. Like all female reproductive organs,
the oviduct undergoes recurrent tissue morphogenesis in response to the cyclical hormonal changes of the
estrous cycle, which is the fundamental hormonal regulator that allows all mammals, including humans, to
become pregnant. The oviduct is lined by a single layer of epithelium which is composed of multiciliated and
secretory cells. The multiciliated cells (MCCs) project hundreds of motile cilia from their apical surface, where
they beat together and are hypothesized to capture the ovulated oocyte and sweep it down the oviduct. The
MCCs remodel dramatically during the estrous cycle: during the first half of the cycle, the percentage of MCCs
increases and peaks at ovulation, after which the percentage of MCCs decreases significantly. While oviduct
epithelial remodeling is known to occur, it is completely unclear how these remodeling events are regulated.
Does oviduct MCC remodeling occur via apoptosis or deciliation? Do stem cells participate in these remodeling
events? In multiciliated tissues, cilia beat together because the tissue is planar polarized. How is planar cell
polarity of the oviduct lost and regained throughout the estrous cycle? Finally, how are these remodeling events
regulated at the genetic level? This proposal seeks to explore oviduct MCC remodeling using a combination of
mouse genetics, high resolution imaging of cell shapes and behaviors, in vivo imaging of oviduct fluid flow, and
unbiased genomic analysis. The work proposed here will provide new insights into the turnover of oviduct
multiciliated cells and the genomic control of oviduct epithelial homeostasis (Aim 1), and the establishment of
planar cell polarity in the oviduct (Aim 2) during the estrous cycle. Understanding the genetic, molecular, and
cellular basis of MCC remodeling of the oviduct during the estrous cycle holds therapeutic promise for treating
female infertility and improving the success rates of in vitro fertilization.
项目概要
尽管子宫内膜异位症和宫外孕等女性生殖疾病普遍存在,但
令人震惊的是,人们对所涉及器官的分子或细胞生物学知之甚少。该提案的重点是
输卵管,因为输卵管是卵巢和子宫之间的管道,是
哺乳动物受精。虽然输卵管是女性生育的关键部位,但输卵管生理学是如何调节的
在遗传、分子和细胞水平上几乎完全未知。与所有女性生殖器官一样,
输卵管响应周期性激素变化而经历反复的组织形态发生
发情周期,这是基本的激素调节剂,使包括人类在内的所有哺乳动物能够
受孕。输卵管内衬有单层上皮,该上皮由多纤毛和
分泌细胞。多纤毛细胞 (MCC) 从其顶端表面投射出数百个活动纤毛,其中
它们一起跳动,并被假设捕获排卵的卵母细胞并将其扫入输卵管。这
MCC 在发情周期期间发生显着重塑:在周期的前半段,MCC 的百分比
增加并在排卵时达到峰值,此后 MCC 的百分比显着下降。而输卵管
已知上皮重塑会发生,但完全不清楚这些重塑事件是如何调节的。
输卵管 MCC 重塑是通过细胞凋亡还是去纤毛发生的?干细胞参与这些重塑吗
事件?在多纤毛组织中,纤毛一起跳动,因为该组织是平面极化的。平面电池怎么样
输卵管极性在整个动情周期中丢失和恢复?最后,这些改造活动怎么样
在基因水平上受到调控?该提案旨在探索结合以下方法进行输卵管 MCC 重塑:
小鼠遗传学、细胞形状和行为的高分辨率成像、输卵管流体流动的体内成像,以及
无偏见的基因组分析。这里提出的工作将为输卵管周转提供新的见解
多纤毛细胞和输卵管上皮稳态的基因组控制(目标 1),以及建立
发情周期期间输卵管中的平面细胞极性(目标 2)。了解遗传、分子和
动情周期期间 MCC 输卵管重塑的细胞基础为治疗带来了治疗希望
女性不孕症,提高体外受精的成功率。
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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