Assessment of reproductive outcomes on adult offspring from in vitro fertilization using a mouse model

项目摘要 辅助生殖技术(ART)是用于治疗的非性交受孕方法 不孕不育并实现怀孕。全世界有多达900万名婴儿因抗逆转录病毒治疗而出生。在 未来几年，随着越来越多的夫妇推迟生育，预计人工辅助生育的数量将会增加。 儿童或不孕不育的发生率更高。ART中使用的程序包括复杂的技术，如 如体外受精(IVF)和卵胞浆内单精子注射，以及不太复杂的程序，如 作为配子和胚胎的冷冻保存和植入前的遗传测试。最近，来自不同部门的工作人员 实验室表明，抗逆转录病毒治疗与母亲和胎儿的健康风险有关，如死产， 早产、宫内发育受限、胎盘异常及其他妊娠并发症。另外， 最近的研究表明，试管受精的后代可以改善代谢和/或心血管结果 在成年的时候。小鼠模型支持这些临床观察，并表明成年试管受精后代 会导致新陈代谢和心血管疾病。辅助生殖中使用的技术有 不断改进以增加怀孕成功率，但新技术的效果尚未得到 在实施之前进行评估。因为生殖系统已经被证明对 宫内发育期间的扰动可能会影响未来的功能，这是本研究的主要目的 建议研究试管受精程序如何影响试管婴儿后代的正常生殖系统功能 并阐明与观察结果有关的潜在遗传和表观遗传机制。因为 雌性和雄性都有独特的途径和生理功能，它们的生殖系统是 综合分析，出于这个原因，本提案的目标1将解决形态、细胞组成、 成年雌性性腺和配子的转录组、组蛋白翻译后修饰和生育能力 后代，而目标2将解决类似的终点在男性。确定体外受精后代中可能的变化 生殖系统很重要，因为任何帮助怀孕的程序都应该 确保一个健康的孩子不会出现未来的并发症和(2)因为试管受精通常被 不育夫妇潜在的不孕不育状况可能会传递给后代，最终导致 依赖试管受精的后代。这项研究中提出的计划将被证明对未来的研究有用。 复杂的组织，也用于识别试管受精影响的机制，这些机制可能在未来被询问 以将对后代的不良影响降至最低。

Project Abstract Assisted Reproductive Technologies (ART) are non-coital methods of conception that are used to treat infertility and achieve a pregnancy. As many as 9 million births worldwide have resulted from ART. In the coming years, it is expected that the number of births by ART will increase as more couples postpone having children or infertility arises on a more regular basis. Procedures used in ART include complex techniques such as in vitro fertilization (IVF) and intracytoplasmic sperm injection, and as well as less complex procedures such as gamete and embryo cryopreservation and preimplantation genetic testing. Recently, work from various laboratories has shown that ART is associated with health risks for mothers and fetuses such as stillbirth, preterm birth, intrauterine growth restriction, abnormal placentation, and other pregnancy complications. Also, more recent studies have shown that IVF offspring can develop metabolic and/or cardiovascular outcomes during adulthood. Mouse models support these clinical observations and have shown that adult IVF offspring can develop metabolic and cardiovascular outcomes. Technologies used in assisted reproduction are continuously refined to increase pregnancy success, but the effects of newer techniques have not been assessed prior to implementation. Because the reproductive system has been shown to be sensitive to perturbations during intrauterine development potentially impacting future functions, the main object of this proposal is to study how IVF procedures affect normal function of reproductive system in IVF offspring in mice and elucidate underlying genetic and epigenetic mechanisms involved in observed outcomes. Because females and males have unique pathways and physiological functions their reproductive systems cannot be analyzed together, for this reason aim 1 of this proposal will address changes in morphology, cell composition, transcriptome, histone posttranslational modifications and fertility in gonads and gametes from adult female offspring, while aim 2 will address similar endpoints in males. Identifying possible alterations in IVF offspring in the reproductive system is important (1) because any procedure use to help achieve a pregnancy should ensure a healthy child which will not develop future complications and (2) because IVF is commonly used by infertile couples the underlying infertility conditions could passed to the offspring ultimately rendering the offspring dependent of IVF. The plan proposed in this fellowship will prove to be useful for future studies of complex tissues and also for identifying mechanisms influenced by IVF that could be interrogated in the future to minimize adverse effects in offspring.