Deciphering the Roles of Endometrial Glycogen Reserves and the Impact of Obesity on Fertility

解读子宫内膜糖原储备的作用以及肥胖对生育力的影响

基本信息

项目摘要

Project Summary Over 40% of pregnancies fail in women, most before or during embryo implantation. During this time, embryos are dependent on secretions into the uterine lumen that contains all of the growth factors and nutrients necessary for embryo development. In particular, embryos need glucose. From fertilization until the morula stage, glucose uptake is low, but without glucose, the embryo degenerates. As embryos approach the blastocyst stage, glucose uptake increases dramatically, providing ATP to the embryo within the hypoxic uterine lumen. The endometrial stroma also uses a large amount of glucose to decidualize. After decidualization, the stroma relies on Warburg metabolism to produce ATP and supplies glucose to the invading embryo. Thus, it is clear that glucose availability must be regulated in a spatiotemporal manner to ensure a successful pregnancy. Finally, obesity leads to reduced fertility in women through, in part, effects on the uterus and its ability to support pregnancy. Most research on endometrial glucose has focused on the role of glucose transporters. However, the endometrium can also transiently store glucose as the macromolecule glycogen. In women, endometrial glycogen concentrations are correlated with fertility, but a direct link between uterine glycogen and fertility has never been established. To investigate this in mice, we collected uteri on proestrus and days post coitum (DPC) 1.5, 3.5, and 5.5. Our preliminary data show that the mouse endometrium stores two distinct glycogen pools: in the uterine epithelium and the uterine decidua. Epithelial glycogen peaked at proestrus and significantly reduced during the preimplantation period. The epithelial expressed glycogen phosphorylase and glucose-6-phosphatase, suggesting the epithelium can catabolize glycogen and secrete the resulting glucose. In contrast, the endometrial stroma stored little glycogen until decidualization, when glycogen content increased 7-fold. Similarly, artificially induced decidualization in hormonally primed mice resulted in a 5-fold increase in glycogen levels. In order to establish a definitive relationship between these distinct pools of glycogen and fertility, we obtained glycogen synthase 1 (GYS1) floxed mice so that we can knockout GYS1 in a tissue-specific manner. Aim 1 will generate an LTFiCre/+ GYS1flox/flox mouse to study the role of epithelial glycogen in glucose secretion and preimplantation embryo survival. Aim 2 will use AMHR2Cre/+ GYS1flox/flox mice to study the role of glycogen in the decidua. Collectively these aims will establish a causative link between the ability of the uterus to store glycogen in the epithelium and decidua and fertility. Aim 3 will use a diet-induced obesity model to study how maternal obesity affects glycogen metabolism in the mouse uterus. We will determine how a 45% and 60% fat diet affects uterine metabolism and fertility in a C57BL/6 mouse model. In vitro, we will determine the effects of hyperglycemia and hyperinsulinemia on decidual glycogen. In summary, this research will evaluate the role of endometrial glycogen stores in support of early pregnancy and assess the potential for maternal obesity to result in dysfunctional endometrial glycogen metabolism.
项目总结

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Matthew J Dean其他文献

Matthew J Dean的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Matthew J Dean', 18)}}的其他基金

The Role of Uterine Glycogen in Establishing a Successful Pregnancy
子宫糖原在成功怀孕中的作用
  • 批准号:
    10725894
  • 财政年份:
    2023
  • 资助金额:
    $ 37.29万
  • 项目类别:
Propylparaben effects on reproductive health of the aging female
对羟基苯甲酸丙酯对老年女性生殖健康的影响
  • 批准号:
    10373441
  • 财政年份:
    2021
  • 资助金额:
    $ 37.29万
  • 项目类别:
Propylparaben effects on reproductive health of the aging female
对羟基苯甲酸丙酯对老年女性生殖健康的影响
  • 批准号:
    10526421
  • 财政年份:
    2021
  • 资助金额:
    $ 37.29万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 37.29万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了