Genetics of Male Infertility: A Marker of Overall Health
男性不育的遗传学:整体健康的标志
基本信息
- 批准号:10613339
- 负责人:
- 金额:$ 162.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2025-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAdoptionAdultAgeBenefits and RisksBiologicalCRISPR/Cas technologyCardiovascular DiseasesCell MaintenanceCenter for Translational Science ActivitiesChildCitiesClinicCollaborationsCommunicationComplementCounselingCouplesDataData Coordinating CenterDevelopmentDiagnosisDiseaseEducationEducation and OutreachEpigenetic ProcessFaculty WorkshopFamilyFamily memberFemaleFertilityGenesGeneticGerm CellsHealthHigh School StudentHumanIndividualInfertilityInstitutionK-12 studentKnowledgeLeadLearning ModuleLife ExpectancyLinkMale InfertilityMalignant NeoplasmsMedicalMedical centerMetabolic syndromeMiddle School StudentMissionMutant Strains MiceMutationNew YorkOregonPatient RecruitmentsPatientsPhenotypePilot ProjectsPoliciesPregnancyProgram DescriptionQuestionnairesRecording of previous eventsReproductionReproductive HealthReproductive MedicineResearchResearch PersonnelScienceSertoli cell only syndromeSomatic CellSpecialized CenterStudentsSumTechnologyTestingTestisTimeTranslatingTranslationsUnited StatesUniversitiesVariantWashingtonWell in selfWorkassisted reproductioncareerclinical developmentclinical diagnosticscomorbiditycomorbidity Indexcostdata exchangediagnostic screeningeffectiveness evaluationepidemiologic dataepigenomefertility preservationgene therapygenetic variantgenome editinggenome sequencinghuman modelidiopathic infertilityimprovedindividualized medicinejunior high schoollaboratory experimentmalemanmedical schoolsmenmouse modelnovelpersonalized medicineprogramsprospectivereproductivesafety and feasibilitysertoli cellstem cell functionstem cellstargeted treatmentteacherunderserved communitywhole genome
项目摘要
Abstract: Overall
Azoospermia impacts 1% of men globally, which translates to 645,000 men between the ages of 20 and 50 in
the United States. It is estimated that genetic causes explain 50% of infertility. Epidemiological data suggest
that fertility status may be a marker of overall health, but the genetic underpinnings are just beginning to be
understood. Improved knowledge about the genetic basis of infertility and associated overall health
comorbidities will aid in the counseling of infertile couples; justify the development of diagnostic
screens; and may lead to patient-specific treatment options. In the current personalized medicine era with
reduced cost whole genome sequencing and facile genome editing technologies, it is feasible to discover
genetic underpinnings of infertility and overall health comorbidities and develop targeted therapies. Project I
will discover genetic variants in men with azoospermia to identify targets for development of clinical diagnostics
or therapy. Project I will use Charlson Comorbidity Index questionnaires to determine whether infertile patients
or their family members have histories of other overall health comorbidities. Project II will validate infertility-
associated genetic variants identified in Project I and characterize the fertility and overall health phenotypes.
Project II will also work collaborate with Project III to determine the impact of epigenetic perturbations on
spermatogonial stem cell function. Project III will develop Sertoli cell and germ cell gene therapies in mouse
models of azoospermia and will produce critical safety and feasibility data to inform the public dialogue on the
risks and benefits of gene therapy in and around the germline. The Pilot project will discover the epigenetic
landscape of germ cells and somatic cells from the testes of fertile versus infertile men. Core A will provide the
administrative oversight and facilitate communications and data exchange among projects and cores to ensure
that this P50 program achieves an impact that is greater than the sum of its parts. The Education and Outreach
Core will maximize the public impact of this P50 by developing hands-on teaching modules to educate middle
school and high school students as well as adults in underserved communities about reproductive medicine
and the genetics of infertility. Modules will be tested and validated in the Pitt Mobile Science lab before
deploying to teacher workshops in St. Louis, Pittsburgh, Ithaca and New York allowing teachers to implement
the modules in their classrooms. Male focused teaching modules will also be shared with P50 centers in
Oregon and at Northwestern to complement their existing female-focused hands-on modules.
文摘:整体
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Human Spermatogenesis: Insights From the Clinical Care of Men With Infertility.
- DOI:10.3389/fendo.2022.889959
- 发表时间:2022
- 期刊:
- 影响因子:5.2
- 作者:
- 通讯作者:
Consensus label propagation with graph convolutional networks for single-cell RNA sequencing cell type annotation.
- DOI:10.1093/bioinformatics/btad360
- 发表时间:2023-06-01
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
High SARS-CoV-2 tropism and activation of immune cells in the testes of non-vaccinated deceased COVID-19 patients.
- DOI:10.1186/s12915-022-01497-8
- 发表时间:2023-02-16
- 期刊:
- 影响因子:5.4
- 作者:Costa, Guilherme M. J.;Lacerda, Samyra M. S. N.;Figueiredo, Andre F. A.;Wnuk, Natalia T.;Brener, Marcos R. G.;Andrade, Lidia M.;Campolina-Silva, Gabriel H.;Kauffmann-Zeh, Andrea;Pacifico, Lucila G. G.;Versiani, Alice F.;Antunes, Maisa M.;Souza, Fernanda R.;Cassali, Geovanni D.;Caldeira-Brant, Andre L.;Chiarini-Garcia, Helio;de Souza, Fernanda G.;Costa, Vivian V.;da Fonseca, Flavio G.;Nogueira, Mauricio L.;Campos, Guilherme R. F.;Kangussu, Lucas M.;Martins, Estefania M. N.;Antonio, Loudiana M.;Bittar, Cintia;Rahal, Paula;Aguiar, Renato S.;Mendes, Barbara P.;Procopio, Marcela S.;Furtado, Thiago P.;Guimaraes, Yuri L.;Menezes, Gustavo B.;Martinez-Marchal, Ana;Orwig, Kyle E.;Brieno-Enriquez, Miguel;Furtado, Marcelo H.
- 通讯作者:Furtado, Marcelo H.
The Sertoli cell expressed gene secernin-1 (Scrn1) is dispensable for male fertility in the mouse.
- DOI:10.1002/dvdy.299
- 发表时间:2021-07
- 期刊:
- 影响因子:2.5
- 作者:Houston, Brendan J.;Nagirnaja, Liina;Merriner, D. Jo;O'Connor, Anne E.;Okuda, Hidenobu;Omurtag, Kenan;Smith, Craig;Aston, Kenneth I.;Conrad, Donald F.;O'Bryan, Moira K.
- 通讯作者:O'Bryan, Moira K.
Germ cell nests in adult ovaries and an unusually large ovarian reserve in the naked mole-rat.
- DOI:10.1530/rep-20-0304
- 发表时间:2021-01
- 期刊:
- 影响因子:0
- 作者:Place NJ;Prado AM;Faykoo-Martinez M;Brieño-Enriquez MA;Albertini DF;Holmes MM
- 通讯作者:Holmes MM
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Kyle Edwin Orwig其他文献
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{{ truncateString('Kyle Edwin Orwig', 18)}}的其他基金
Genetics of Male Infertility: A Marker of Overall Health
男性不育的遗传学:整体健康的标志
- 批准号:
10005443 - 财政年份:2019
- 资助金额:
$ 162.38万 - 项目类别:
Genetics of Male Infertility: A Marker of Overall Health
男性不育的遗传学:整体健康的标志
- 批准号:
10379346 - 财政年份:2019
- 资助金额:
$ 162.38万 - 项目类别:
Reproductive Development from Gonads to Fetuses
从性腺到胎儿的生殖发育
- 批准号:
10163223 - 财政年份:2017
- 资助金额:
$ 162.38万 - 项目类别:
Cellular Mechanisms of Chemotherapy-induced Male Infertility: Stem Cell or Niche?
化疗引起男性不育的细胞机制:干细胞还是利基?
- 批准号:
8636803 - 财政年份:2014
- 资助金额:
$ 162.38万 - 项目类别:
Preserving Male Fertility After Cancer Therapy
癌症治疗后保持男性生育能力
- 批准号:
8878315 - 财政年份:2014
- 资助金额:
$ 162.38万 - 项目类别:
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