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

项目总结/摘要 电子尼古丁递送系统（ENDS）或电子香烟广泛用于吸烟者。 今天，尽管缺乏关于他们安全的信息，但他们仍然是一个国家。特别是ENDS的使用 孕妇吸烟是普遍的，因为怀孕期间吸烟与 流产和胎儿死亡然而，关于ENDS使用期间的安全性知之甚少。 怀孕ENDS由含有丙二醇和蔬菜混合物的液体组成 甘油与添加的调味剂、尼古丁和增稠剂一起加热，雾化， 并吸入。用调味剂和增稠剂补充ENDS可以显著地 提高毒性水平，从而损害微调的生物过程，如怀孕。 在妊娠开始时，子宫间质和上皮以复杂的方式沟通， 协调分子和激素信号传导事件以协调 胚胎植入后，胎儿来源的滋养层细胞侵入母体组织， 重塑螺旋动脉开始胎盘的形成最近公布的数据 是第一个描述ENDS暴露延长怀孕时间并导致 胚胎着床延迟。我还确定ENDS的暴露引起了戏剧性的 植入时的转录组转变。然而，没有研究进一步研究 导致植入延迟的机制。ENDS暴露被鉴定为损害滋养层细胞 在体外的功能，但没有在体内的研究已经检查胎盘的发展。虽然大多数 ENDS用户喜欢添加风味，没有研究检查ENDS与风味使用或 妊娠期使用增稠剂。因此，迫切需要进一步研究如何结束 会影响怀孕。该提案旨在：（1）测试添加剂的ENDS如何影响生育力 和胎盘发育，2.）研究ENDS驱动机制导致延迟 使用体外人上皮类器官模型植入，和3.）确定时间， 体内ENDS诱导的胚胎着床延迟的原因。该提案提供了详细的 计划研究ENDS如何调节生育和早孕成功，并建议 验证ENDS介导的延迟着床的分子机制。这项研究可以建议 公众对妊娠期使用ENDS的谨慎措施，可以扩大 我们对调节植入成功的机制的理解， 患有不孕症或复发性着床失败。

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.