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

使用小鼠模型评估体外受精成年后代的生殖结果

• 批准号: 10389163
• 负责人: Eric ALEJANDRO Rhon Calderon
• 金额: $ 6.86万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10389163
• 关键词: Abnormal placentation; Academia; Address; Adult; Adult Children; Adverse effects; Affect; Age; Aging; Androgen Receptor; Assisted Reproductive Technology; Birth; Breeding; Cardiovascular system; Cells; Child; Clinic; Clinical; Complex; Conceptions; Couples; DNA Methylation; Data; Dehydroepiandrosterone Sulfate; Development; Ensure; Epigenetic Process; Estrogen Receptor beta; Exhibits; Fellowship; Female; Fertility; Fertilization in Vitro; Fetal Growth Retardation; Fetus; Focus Groups; Future; Gene Expression; Genes; Genetic; Germ Cells; Gland; Goals; Gonadal structure; Health; Histologic; Histones; Human; Individual; Infertility; Inherited; Injections; Intracytoplasmic Sperm Injections; Laboratories; Lead; Life; Link; Litter Size; Liver; Longevity; Luteinizing Hormone; Male Genital Organs; Metabolic; Methodology; Methods; Methylation; Morphology; Mothers; Mus; Organism; Outcome; Ovarian; Ovarian aging; Ovary; Parents; Pathway interactions; Physiological; Physiology; Post-Translational Protein Processing; Pregnancy; Pregnancy Complications; Preimplantation Diagnosis; Premature Birth; Premature Ovarian Failure; Procedures; Proteins; Proteome; Reproductive system; Research; Research Personnel; Reserve Cell; Risk; Running; Severities; Sex Ratio; Sexual Development; Site-Directed Mutagenesis; Somatic Cell; System; Techniques; Technology; Teenagers; Testis; Tissues; Training; Uterus; Work; assisted reproduction; bisulfite; bone age; embryo cryopreservation; embryo culture; female reproductive system; girls; in vitro Model; leydig interstitial cell; male; methylation pattern; methylome; mouse model; offspring; receptor expression; reproductive; reproductive function; reproductive outcome; sertoli cell; sex; sperm cell; stillbirth; success; tool; transcriptome; transcriptome sequencing

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.

项目摘要 辅助生殖技术（ART）是非性交受孕方法，用于治疗 不孕症并实现怀孕。全球有多达 900 万人通过 ART 出生。在 未来几年，随着越来越多的夫妇推迟生育，预计通过 ART 分娩的人数将会增加 儿童或不孕症的发生更加频繁。 ART 中使用的程序包括复杂的技术，例如 如体外受精 (IVF) 和胞浆内单精子注射，以及不太复杂的程序，例如 如配子和胚胎冷冻保存以及植入前基因检测。最近，来自不同方面的工作 实验室表明，ART 与母亲和胎儿的健康风险有关，例如死产、 早产、宫内生长受限、胎盘异常和其他妊娠并发症。还， 最近的研究表明，体外受精后代可以产生代谢和/或心血管结局 成年期间。小鼠模型支持这些临床观察结果，并表明成年 IVF 后代 可以产生代谢和心血管结果。辅助生殖中使用的技术有 不断改进以提高怀孕成功率，但新技术的效果尚未得到证实 实施前进行评估。因为生殖系统已被证明对 子宫内发育过程中的干扰可能会影响未来的功能，这是本研究的主要目标 提案是研究体外受精程序如何影响小鼠体外受精后代生殖系统的正常功能 并阐明观察到的结果所涉及的潜在遗传和表观遗传机制。因为 女性和男性具有其生殖系统无法比拟的独特途径和生理功能 综合分析，出于这个原因，该提案的目标 1 将解决形态、细胞组成、 成年女性性腺和配子的转录组、组蛋白翻译后修饰和生育力 后代，而目标 2 将解决男性的类似终点。识别 IVF 后代中可能发生的改变 生殖系统很重要 (1) 因为任何用于帮助怀孕的手术都应该 确保孩子健康，未来不会出现并发症；(2) 因为体外受精 (IVF) 通常用于 不孕夫妇潜在的不孕状况可能会遗传给后代，最终导致 后代依赖体外受精。本研究金中提出的计划将被证明对未来的研究有用 复杂的组织，也可用于识别受 IVF 影响的机制，这些机制可以在未来进行研究 以尽量减少对后代的不利影响。