Generation of a Model to Study Uterine Gland Function
Generation of a Model to Study Uterine Gland Function
批准号:
9360767
负责人:
THOMAS E SPENCER
金额:
$19.19万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-28 至 2019-08-31
关键词:
3&apos Untranslated RegionsAddressAdultAffectAnimal ModelApplications GrantsBioinformaticsBiologicalBiologyCRISPR/Cas technologyCell modelCellsCharacteristicsComplicationConceptusDecidual Cell ReactionsDevelopmentDevelopmental BiologyDiagnosisDiseaseDysplasiaEndometrial adenocarcinomaEndometriumEnterobacteria phage P1 Cre recombinaseEpitheliumFemaleFertilityGenerationsGenesGenetic ModelsGenome engineeringGenomicsGlandGoalsHealthHormone ResponsiveHumanInfertilityKnock-in MouseKnowledgeMessenger RNAModelingMusNIH Program AnnouncementsNatural regenerationOvarian Steroid HormoneParentsPathway interactionsPeptide HydrolasesPregnancyPregnancy ComplicationsPregnancy MaintenancePregnancy lossPreventionProcessPubertyPublishingRecurrenceRegulationRegulatory ElementReporterReproductionResearchResearch PersonnelResearch Project GrantsResearch ProposalsRoleSerineSerine ProteaseStromal CellsStudy modelsTissuesTrainingTranslatingUnited States National Institutes of HealthUterine CancerUterine GlandUterusWomanWomen&aposs Healthblastocystendometriosisfunctional genomicshuman tissueimplantationimprovedinfertility treatmentinterestknockout animalmouse modelnegative affectnoveloverexpressionpreventprogramsrecombinasereproductive tractsuccesstranscription factortranscriptometranscriptome sequencinguterine receptivityuterus endometriosis
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Infertility and pregnancy loss are common health disorders affecting women. Uterine glands have
important biological roles in fertility, dysplasia and disease. Pregnancy loss is the most common
complication of human gestation, and recurrent pregnancy loss and infertility are observed in uterine
gland knockout animal models. Uterine glandular epithelia (GE) and, by inference, their secretions
have biological roles in uterine receptivity, blastocyst/conceptus survival and implantation, and
stromal cell decidualization- all essential processes for the establishment and maintenance of
pregnancy. However, uterine gland biology research is hampered by the lack of suitable mouse
models to conditionally delete or overexpress genes specifically in the GE of the adult uterus. The
goal of this proposal is to address that problem. Prss29 (protease, serine 29 or implantation serine
proteinase gene two) is a gene expressed robustly and specifically after puberty in the GE of the adult
mouse uterus and not in other female reproductive tract tissues. In Aim 1, improved Cre recombinase
(iCre) will be inserted into the 3’ untranslated region of the Prss29 gene using CRISPR/Cas9 genome
engineering. Activity and cell-specific expression of iCre will be determined in the developing and
adult tissues using Rosa26 reporter mice. Aim 2 is to establish and validate the usefulness of Prss29-
iCre mice for study of adult uterine gland function. Forkhead box a2 (Foxa2) is specifically expressed
in the GE of the adult mouse and human uterus and has a potential biological role in regulation of
ovarian steroid hormone responsive genes and GE function during pregnancy. Prss29-iCre mice will
be used to conditionally delete Foxa2 in the adult uterus and determine its impact on fertility and
pregnancy. Prss29-iCre mice will be used in conjuction with RiboTag mice to isolate actively
translated mRNAs, which will be sequenced to uncover the GE active transcriptome of pregnancy.
This application specifically targets NIH program announcement PA-13-303 entitled “NIH
Exploratory/Developmental Research Grant Program (Parent R21)” that encourages research grant
applications to support the early and conceptual stages of a project. At the conclusion of these
studies, we expect to have generated a novel mouse model useful for the study of uterine gland
biology, regeneration, and disease and fill a significant gap in our existing knowledge of uterine gland
function during pregnancy.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1210/en.2018-00158
发表时间:
2018-04
期刊:
Endocrinology
影响因子:
4.8
作者:
[Peng Wang;San-pin Wu;K. Brooks;A. M. Kelleher;Jessica Milano-Foster;F. DeMayo;T. Spencer]
通讯作者:
Peng Wang;San-pin Wu;K. Brooks;A. M. Kelleher;Jessica Milano-Foster;F. DeMayo;T. Spencer
Endometrial Basis for Infertility in Women with Recurrent Implantation Failure and Pregnancy Loss
-
批准号:10642892
-
项目类别:
-
资助金额:$65.36万
-
财政年份:2021
-
负责人:THOMAS E SPENCER
-
依托单位:
Biological Role of Uterine Glands in Pregnancy
-
批准号:10200105
-
项目类别:
-
资助金额:$31.52万
-
财政年份:2018
-
负责人:THOMAS E SPENCER
-
依托单位:
Biological Role of Uterine Glands in Pregnancy
-
批准号:9761556
-
项目类别:
-
资助金额:$32.16万
-
财政年份:2018
-
负责人:THOMAS E SPENCER
-
依托单位:
Biological Role of Uterine Glands in Pregnancy
-
批准号:9977233
-
项目类别:
-
资助金额:$32.16万
-
财政年份:2018
-
负责人:THOMAS E SPENCER
-
依托单位:
Biological Role of Endometrial Glands in Uterine Function
-
批准号:9095068
-
项目类别:
-
资助金额:$18.3万
-
财政年份:2013
-
负责人:THOMAS E SPENCER
-
依托单位:
System biology approach to understand endometrial receptivity & pregnancy loss
-
批准号:8514668
-
项目类别:
-
资助金额:$26.2万
-
财政年份:2012
-
负责人:THOMAS E SPENCER
-
依托单位:
System biology approach to understand endometrial receptivity & pregnancy loss
-
批准号:9128673
-
项目类别:
-
资助金额:$32.29万
-
财政年份:2012
-
负责人:THOMAS E SPENCER
-
依托单位:
Systems biology approach to understand endometrial receptivity & pregnancy loss
-
批准号:8335206
-
项目类别:
-
资助金额:$22.33万
-
财政年份:2012
-
负责人:THOMAS E SPENCER
-
依托单位:
Endogenous Retroviruses and Placental Morphogenesis
-
批准号:8299715
-
项目类别:
-
资助金额:$22.09万
-
财政年份:2011
-
负责人:THOMAS E SPENCER
-
依托单位:
Endogenous Retroviruses and Placental Morphogenesis
-
批准号:7196892
-
项目类别:
-
资助金额:$25.2万
-
财政年份:2007
-
负责人:THOMAS E SPENCER
-
依托单位:
Endogenous Retroviruses and Placental Morphogenesis
-
批准号:7415164
-
项目类别:
-
资助金额:$23.46万
-
财政年份:2007
-
负责人:THOMAS E SPENCER
-
依托单位:
Genetic Regulation of Postnatal Uterine Morphogenesis and Function
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批准号:7304868
-
项目类别:
-
资助金额:$18.19万
-
财政年份:2007
-
负责人:THOMAS E SPENCER
-
依托单位:
Endogenous Retroviruses and Placental Morphogenesis
-
批准号:7576695
-
项目类别:
-
资助金额:$23.39万
-
财政年份:2007
-
负责人:THOMAS E SPENCER
-
依托单位:
Genetic Regulation of Postnatal Uterine Morphogenesis and Function
-
批准号:7471414
-
项目类别:
-
资助金额:$21.39万
-
财政年份:2007
-
负责人:THOMAS E SPENCER
-
依托单位:
Endogenous Retroviruses and Placental Morphogenesis
-
批准号:7791447
-
项目类别:
-
资助金额:$23.04万
-
财政年份:2007
-
负责人:THOMAS E SPENCER
-
依托单位:
MECHANISMS REGULATING UTERINE MORPHOGENESIS
-
批准号:6333400
-
项目类别:
-
资助金额:$19.44万
-
财政年份:2001
-
负责人:THOMAS E SPENCER
-
依托单位:
MECHANISMS REGULATING UTERINE MORPHOGENESIS
-
批准号:6637035
-
项目类别:
-
资助金额:$19.44万
-
财政年份:2001
-
负责人:THOMAS E SPENCER
-
依托单位:
MECHANISMS REGULATING UTERINE MORPHOGENESIS
-
批准号:6729923
-
项目类别:
-
资助金额:$19.44万
-
财政年份:2001
-
负责人:THOMAS E SPENCER
-
依托单位:
MECHANISMS REGULATING UTERINE MORPHOGENESIS
-
批准号:6521255
-
项目类别:
-
资助金额:$19.44万
-
财政年份:2001
-
负责人:THOMAS E SPENCER
-
依托单位:
TARGETED DISRUPTION OF STEROID RECEPTOR COACTIVATOR ONE
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批准号:2196557
-
项目类别:
-
资助金额:$1.28万
-
财政年份:1997
-
负责人:THOMAS E SPENCER
-
依托单位:
海外基金