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

项目摘要/摘要 电子烟碱传递系统(END)或电子烟广泛应用于 尽管关于他们的安全的信息很少，但他们今天仍然是一个国家。尤其是，结束了使用 怀孕妇女吸烟的情况很普遍，因为怀孕期间吸烟与 流产和胎儿死亡。然而，人们对终端使用过程中的安全性知之甚少。 怀孕了。Ends是由含有丙二醇和蔬菜混合物的液体组成的 甘油，添加调味料、尼古丁和增稠剂，加热，雾化， 并被吸入。在末端添加香料和增稠剂可以极大地 增加毒性水平，从而损害微调的生物过程，如怀孕。 在怀孕初期，子宫间质和子宫上皮在一个复合体中沟通。 协调分子和激素信号事件以协调植入 胚胎。植入后，胎儿来源的滋养层细胞侵入母体组织， 重建螺旋动脉，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延长怀孕时间并导致 胚胎植入延迟。我还决定曝光Ends会引发戏剧性的 在植入时发生转录转移。然而，还没有研究进一步检查 导致植入延迟的机制。末端暴露被确定为损害滋养层细胞 在体外发挥作用，但还没有体内研究检查胎盘的发育。尽管大多数 终端用户喜欢添加口味，还没有研究检查终端与口味的使用或 妊娠增稠剂。因此，迫切需要进一步研究如何结束。 会影响怀孕。这项提案旨在1.)测试添加剂对生育率的影响 和胎盘发育，2)调查导致延迟的末端驱动机制 使用体外人上皮类器官模型进行植入，以及3.确定时间和 体内END诱导胚胎延迟着床的原因。这份提案提供了一个详细的 计划研究Ends如何调节生育和早孕成功，并建议 验证END介导的延迟着床的分子机制。这项研究可以为我们提供建议 公众对怀孕期间使用Ends的谨慎程度观察并可以扩大 我们对植入成功的调控机制的理解，造福于女性 经历不孕不育或反复发生的植入失败。

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.