Investigating Implications of E-Cigarettes on Pregnancy Success and Reproductive Fitness

研究电子烟对怀孕成功和生殖健康的影响

基本信息

批准号：
10401483
负责人：
Margeaux Wetendorf Marbrey
金额：
$ 10.16万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-05 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10401483
关键词：
Affect Agonist Arteries Benchmarking Biological Process Buffers CXCL12 gene CXCR4 gene Cell Differentiation process Cell physiology Cells Cessation of life Cigarette Community Health Complex Dangerousness Data Decidua Delayed Embryo Implantation Electronic Nicotine Delivery Systems Electronic cigarette Embryo Embryo Transfer Embryonic Development Endometrial Enzymes Epithelial Event Exhibits Exposure to Faculty Fertility Fertility Rates Fetal Death Fetal Growth Retardation Fetal Weight Fetal health Flavoring Foundations Gene Expression Goals Hormonal Human Immune Impairment In Vitro Infertility Inhalation Invaded Knowledge Liquid substance Litter Size Measures Mediating Modeling Molecular Mus Nicotine Organoids Pathology Pathway interactions Patients Placenta Placentation Positioning Attribute Pregnancy Pregnant Women Process Propylene Glycols Prostaglandins Public Health Publishing Recurrence Regulation Reporting Research Resources Safety Sampling Signal Pathway Signal Transduction Spiral Artery of the Endometrium Spontaneous abortion Stromal Cells Supplementation System Testing Time Tissues Toxic effect Uterus Vascular Permeabilities Vegetables Vitamin E Acetate Woman aerosolized antagonist chemokine chemokine receptor cigarette smoking early pregnancy early pregnancy loss electronic cigarette use experience experimental study failure Implantation fetal hormonal signals hypertensive immunoregulation implantation improved in vitro Model in vivo knock-down malformation natural Blastocyst Implantation pregnancy disorder protein expression recruit reproductive fitness reproductive system disorder smoking during pregnancy success tenure track toxicant transcriptomics trophoblast uterine receptivity vapor vegetable glycerin

Affect Agonist Arteries Benchmarking Biological Process Buffers CXCL12 gene CXCR4 gene Cell Differentiation process Cell physiology Cells Cessation of life Cigarette Community Health Complex Dangerousness Data Decidua Delayed Embryo Implantation Electronic Nicotine Delivery Systems Electronic cigarette Embryo Embryo Transfer Embryonic Development Endometrial Enzymes Epithelial Event Exhibits Exposure to Faculty Fertility Fertility Rates Fetal Death Fetal Growth Retardation Fetal Weight Fetal health Flavoring Foundations Gene Expression Goals Hormonal Human Immune Impairment In Vitro Infertility Inhalation Invaded Knowledge Liquid substance Litter Size Measures Mediating Modeling Molecular Mus Nicotine Organoids Pathology Pathway interactions Patients Placenta Placentation Positioning Attribute Pregnancy Pregnant Women Process Propylene Glycols Prostaglandins Public Health Publishing Recurrence Regulation Reporting Research Resources Safety Sampling Signal Pathway Signal Transduction Spiral Artery of the Endometrium Spontaneous abortion Stromal Cells Supplementation System Testing Time Tissues Toxic effect Uterus Vascular Permeabilities Vegetables Vitamin E Acetate Woman aerosolized antagonist chemokine chemokine receptor cigarette smoking early pregnancy early pregnancy loss electronic cigarette use experience experimental study failure Implantation fetal hormonal signals hypertensive immunoregulation implantation improved in vitro Model in vivo knock-down malformation natural Blastocyst Implantation pregnancy disorder protein expression recruit reproductive fitness reproductive system disorder smoking during pregnancy success tenure track toxicant transcriptomics trophoblast uterine receptivity vapor vegetable glycerin

展开

项目摘要

Project Summary/Abstract Electronic nicotinic delivery systems (ENDS) or e-cigarettes are widely used in the nation today, despite a paucity of information regarding their safety. In particular, ENDS usage by pregnant women is prevalent, as cigarette smoking during pregnancy is associated with miscarriage and fetal death. However, little is known regarding the safety of ENDS use during pregnancy. ENDS is made up of a liquid containing a mixture of propylene glycol and vegetable glycerine with additions of flavorings, nicotine, and thickening agents that is heated, aerosolized, and inhaled. Supplementation of ENDS with flavors and thickening agents can dramatically enhance the toxicity level and thus, impair fine-tuned biological processes such as pregnancy. At the start of pregnancy, the uterine stroma and epithelium communicate in a complex orchestration of molecular and hormone signaling events to coordinate the implantation of an embryo. After implantation, the fetal-derived trophoblast cells invade into the maternal tissue to remodel the spiral arteries, initiating the formation of the placenta. My recently published data was the first to describe that ENDS exposure elongated the timing of pregnancy and caused a delay in embryo implantation. I also determined ENDS exposure elicited a dramatic transcriptomic shift at the time of implantation. However, no studies have further examined the mechanism causing implantation delay. ENDS exposure was identified to impair trophoblast cell function in vitro, yet no in vivo studies have examined placental development. Although most ENDS users enjoy the addition of flavors, no studies have examined ENDS with flavor usage or thickening agents on pregnancy. Thus, there is an urgent need to further examine how ENDS can influence pregnancy. This proposal aims to 1.) test how ENDS with additives affects fertility and placental development, 2.) investigate the ENDS-driven mechanisms resulting in delayed implantation using an in vitro human epithelial organoid model, and 3.) determine the timing and cause of in vivo ENDS-induced delayed embryo implantation. This proposal provides a detailed plan to examine how ENDS regulates fertility and early pregnancy success and proposes to validate ENDS-mediated molecular mechanisms delaying implantation. This study can advise the public on the measure of caution observed for ENDS usage in pregnancy and can expand our understanding of mechanisms that regulate implantation success, benefitting women experiencing infertility or recurrent implantation failure.

项目摘要/摘要电子烟碱输送系统（末端）或电子烟被广泛用于今天的国家，尽管关于其安全性的信息很少。特别是用法孕妇很普遍，因为怀孕期间吸烟与流产和胎儿死亡。但是，关于目的的安全性在怀孕。末端由含有丙二醇和蔬菜的混合物的液体组成甘油，添加调味剂，尼古丁和增厚剂，并加热，雾化，燃气，并吸入。用口味和增厚剂补充末端可以极大地提高毒性水平，从而损害诸如妊娠等微调生物学过程。怀孕开始时，子宫基质和上皮在复合物中进行交流分子和激素信号事件的管弦乐，以协调植入胚胎。植入后，胎儿衍生的滋养细胞细胞侵入母体组织重塑螺旋动脉，启动胎盘的形成。我最近发布的数据是第一个描述末端暴露的人，延长了怀孕的时机，并引起了延迟胚胎植入。我还确定结束暴露引起了戏剧性植入时的转录组移动。但是，尚无研究进一步研究导致植入延迟的机制。识别出末端暴露以损害滋养细胞体外功能，但没有体内研究检查胎盘发育。虽然大多数用户最终享受添加口味，没有研究以风味使用或怀孕时增厚剂。因此，迫切需要进一步研究会影响怀孕。该提案的目的是1.）测试添加剂的目的如何影响生育和胎盘发育，2。）研究导致延迟的端驱动机制使用体外人类上皮器官模型的植入和3.）确定时间和体内末端引起的延迟胚胎植入的原因。该建议提供了详细的计划检查目的如何调节生育能力和早期怀孕的成功，并提议验证末端介导的分子机制延迟植入。这项研究可以建议公众在怀孕期间观察到的谨慎态度，可以扩大我们对调节植入成功的机制的理解，使妇女受益经历不孕或反复植入失败。