Mechanisms of Gestation Length Timing in Mice
Mechanisms of Gestation Length Timing in Mice
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211150949
- ISBN
- 9798381972078
- DDC
- 574
- 저자명
- McIntyre, Tara.
- 서명/저자
- Mechanisms of Gestation Length Timing in Mice
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 247 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
- 주기사항
- Advisor: Fisher, Susan.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약Timing mechanisms in biology remain poorly understood. As one prime example, little is known about the mechanisms that specify how long the gestating uterus will remain quiescent before entering labor. Our lack of insight into this fundamental question, which applies to all mammalian species, also limits investigation into potential causes of preterm labor, a major human pregnancy complication. My dissertation work provides evidence that gestation length in mice is determined by an epigenetic timer that runs autonomously within the fibroblasts of the pregnant uterus. The timer is set during the peri-implantation period when select loci establish appropriate levels of the repressive histone mark H3K27me3. These loci then progressively lose H3K27me3, thereby scheduling the uterine cell state transitions and associated gene expression changes of late gestation that are the proximal mediators of luteolysis (progesterone withdrawal) and labor onset. Initial overwinding of the timer via genetic ablation of the histone demethylase KDM6B delays these transitions and extends gestation length. My findings also demonstrate requirements for KDM6 demethylases in inflammation-induced preterm labor, and suggest potential requirements for KDM6B in the uterine-intrinsic pathways of parturition that are distinct from luteolysis. These results unexpectedly implicate epigenetic pathways in fibroblasts as a top-level determinant of both normal and pathological parturition mechanisms. We anticipate that further dissection of the ways such fibroblast programming controls gestation length may suggest novel approaches for improving human pregnancy outcomes.
- 일반주제명
- Biology
- 키워드
- epigenetics
- 키워드
- fibroblasts
- 키워드
- H3K27me3
- 키워드
- parturition
- 키워드
- pregnancy
- 키워드
- uterus
- 기타저자
- University of California, San Francisco Biomedical Sciences
- 기본자료저록
- Dissertations Abstracts International. 85-09B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798381972078
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aMcIntyre, Tara.▼0(orcid)0000-0001-6670-9977
■24510▼aMechanisms of Gestation Length Timing in Mice
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a247 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-09, Section: B.
■500 ▼aAdvisor: Fisher, Susan.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aTiming mechanisms in biology remain poorly understood. As one prime example, little is known about the mechanisms that specify how long the gestating uterus will remain quiescent before entering labor. Our lack of insight into this fundamental question, which applies to all mammalian species, also limits investigation into potential causes of preterm labor, a major human pregnancy complication. My dissertation work provides evidence that gestation length in mice is determined by an epigenetic timer that runs autonomously within the fibroblasts of the pregnant uterus. The timer is set during the peri-implantation period when select loci establish appropriate levels of the repressive histone mark H3K27me3. These loci then progressively lose H3K27me3, thereby scheduling the uterine cell state transitions and associated gene expression changes of late gestation that are the proximal mediators of luteolysis (progesterone withdrawal) and labor onset. Initial overwinding of the timer via genetic ablation of the histone demethylase KDM6B delays these transitions and extends gestation length. My findings also demonstrate requirements for KDM6 demethylases in inflammation-induced preterm labor, and suggest potential requirements for KDM6B in the uterine-intrinsic pathways of parturition that are distinct from luteolysis. These results unexpectedly implicate epigenetic pathways in fibroblasts as a top-level determinant of both normal and pathological parturition mechanisms. We anticipate that further dissection of the ways such fibroblast programming controls gestation length may suggest novel approaches for improving human pregnancy outcomes.
■590 ▼aSchool code: 0034.
■650 4▼aBiology
■653 ▼aepigenetics
■653 ▼afibroblasts
■653 ▼aH3K27me3
■653 ▼aparturition
■653 ▼apregnancy
■653 ▼auterus
■690 ▼a0306
■71020▼aUniversity of California, San Francisco▼bBiomedical Sciences.
■7730 ▼tDissertations Abstracts International▼g85-09B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160281▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
