Paternal exposure to dioxins and offspring sex ratio distortion
父亲接触二恶英与后代性别比扭曲
基本信息
- 批准号:8969872
- 负责人:
- 金额:$ 24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-15 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:AdolescentAdultAdverse effectsAffectAgricultureAllelesAnimalsAryl Hydrocarbon ReceptorBarker HypothesisBiologicalBiological PreservationBirthCellular biologyComplexCryptorchidismDevelopmentDioxinsDiseaseEcologyEffectivenessEnvironmentExhibitsExposure toFemaleFertilizationFundingFutureGene ExpressionGenesGeneticGenetic PolymorphismGenetic TranscriptionGerm CellsGoalsHaploidyHealthHumanHypospadiasInbred Strains MiceKnowledgeLeadLearningMale InfertilityMalignant neoplasm of testisMammalsMessenger RNAModelingMusPaternal ExposurePharmacologic SubstancePoisonPredispositionProlineProteinsRNARelative (related person)ReproductionSeminal fluidSex PreselectionSex RatioSpermatidsTestingTetrachlorodibenzodioxinToxic Environmental SubstancesX ChromosomeX-Bearing SpermsY ChromosomeY-Bearing Spermsabstractingassisted reproductionbasedifferential expressioninsightmaleoffspringpublic health relevancereproductiveresearch studysexsperm celltranscription factortransmission processzygote
项目摘要
DESCRIPTION (provided by applicant): Paternal exposure to dioxins and offspring sex ratio distortion Project Summary/Abstract It is widely recognized that the rates of certain male reproductive disorders (such as impaired semen quality, testicular cancer, cryptorchidism, and hypospadias) are increasing and that these changes may be caused in large part by toxic substances in the environment. In this proposal, one of these specific effects, the complex biological mechanism of sex ratio distortion caused in the offspring of human and animal males exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), will be elucidated. The broad, long-term goal is to define the mechanism that causes transmission distortion in the sex ratios of offspring sired by male mammals that have been exposed to compounds such as TCDD. The hypothesis to be tested is: Certain environmental toxicants decrease the relative effectiveness of Y sperm by altering the ability of conjoined, synchronously developing haploid spermatids to share RNA and/or proteins across intercellular bridges or by differentially impacting gene expression from the X chromosome- bearing spermatids (X spermatids) or Y chromosome-bearing spermatids (Y spermatids). Specific Aim 1 is to enhance the experimental conditions for the study of sex ratio transmission distortion resulting from paternal dioxin exposure. The hypothesis to be tested is: As a consequence of TCDD exposure, inbred strains of mice that express highly responsive AHRs will exhibit greater sex ratio distortion than strains that have AHRs that are less responsive to TCDD. We will optimize the conditions for observing the sex ratio distortion and expect to find that AHR is required for the TCDD-induced sex ratio distortion.
Specific Aim 2 is to elucidate the differences in specific mRNA levels between X and Y spermatids that have or have not been exposed to TCDD. The hypothesis to be tested is: TCDD, acting through the AHR, alters mRNA levels of a gene or genes affecting the relative functionality the X and Y sperm. We anticipate that specific genes are differentially expressed that influence the ability of X or Y sperm to fertilize an egg. Producing the proper sex ratio in offspring is important to biomedicine (human health consequences), ecology (preservation of species), and, potentially, agriculture (as a means for offspring sex selection/enrichment). Using the mouse as a surrogate for humans in these studies, we will gain important knowledge that will be applicable to assisted reproduction, germ cell biology, and the developmental origins of adult disease. In the short term, the study of the effects on environmental toxicants on human and animal reproduction will uncover the mechanism of sex ratio distortion in dioxin- exposed humans. In the long run, the experiments funded by this project could lead to the development of beneficial pharmaceutical compounds to increase the ratio of female births of agriculturally important species.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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George L. Gerton其他文献
Live imaging analysis of mouse sperm acrosomal exocytosis
- DOI:
10.1016/j.ydbio.2008.05.299 - 发表时间:
2008-07-15 - 期刊:
- 影响因子:
- 作者:
Mariano G. Buffone;Esmeralda Rodriguez-Miranda;George L. Gerton - 通讯作者:
George L. Gerton
George L. Gerton的其他文献
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{{ truncateString('George L. Gerton', 18)}}的其他基金
Paternal exposure to dioxins and offspring sex ratio distortion
父亲接触二恶英与后代性别比扭曲
- 批准号:
9126551 - 财政年份:2015
- 资助金额:
$ 24万 - 项目类别:
A Program to Promote Diversity within the American Society of Andrology
促进美国男科学会多样性的计划
- 批准号:
8511627 - 财政年份:2012
- 资助金额:
$ 24万 - 项目类别:
A Program to Promote Diversity within the American Society of Andrology
促进美国男科学会多样性的计划
- 批准号:
8726388 - 财政年份:2012
- 资助金额:
$ 24万 - 项目类别:
A Program to Promote Diversity within the American Society of Andrology
促进美国男科学会多样性的计划
- 批准号:
8402722 - 财政年份:2012
- 资助金额:
$ 24万 - 项目类别:
2009 Fertilization and Activation of Development Gordon Research Conference
2009年施肥与发育激活戈登研究会议
- 批准号:
7743880 - 财政年份:2009
- 资助金额:
$ 24万 - 项目类别:
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