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: 10652260
• 负责人: Eric ALEJANDRO Rhon Calderon
• 金额: $ 7.63万
• 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/10652260
• 关键词: Abnormal placentation; Academia; 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; 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; human old age (65+); improved; 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）是用于治疗 不育并实现怀孕。全球多达900万个出生是由艺术造成的。在 未来几年，随着越来越多的夫妇推迟，艺术的出生人数将会增加 儿童或不育会定期出现。艺术中使用的程序包括复杂技术 作为体外受精（IVF）和胞质内精子注射，以及不太复杂的程序 作为配子和胚胎冷冻保存以及植入前基因检测。最近，来自各种工作 实验室表明，艺术与母亲和胎儿的健康风险有关，例如死产， 早产，宫内生长限制，异常胎盘和其他妊娠并发症。还， 最近的研究表明，IVF后代可以发展代谢和/或心血管结局 在成年期。鼠标模型支持这些临床观察结果，并表明成年IVF后代 可以发展代谢和心血管结局。用于辅助生殖的技术是 不断完善以提高怀孕成功，但较新技术的影响尚未 在实施之前进行评估。因为已显示生殖系统对 宫内发育过程中的扰动可能会影响未来的功能，这是其中的主要对象 建议是研究IVF程序如何影响小鼠IVF后代生殖系统的正常功能 并阐明与观察结果有关的潜在遗传和表观遗传机制。因为 女性和男性具有独特的途径和生理功能，其生殖系统不可能是 共同分析，因此，本提案的目标1将解决形态学，细胞组成， 成年女性的转录组，翻译后的修饰和性腺的生育能力 后代，而AIM 2将解决男性的类似终点。确定IVF后代可能发生的更改 生殖系统很重要（1），因为任何可以帮助实现怀孕的程序都应使用 确保一个不会发展未来并发症的健康孩子，（2），因为IVF通常使用 不育夫妇的基本不育条件可能传递给后代最终渲染 IVF的后代。该奖学金中提出的计划将被证明对以后的研究很有用 复杂的组织以及识别受IVF影响的机制，将来可能会受到询问 最大程度地减少后代的不良影响。