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）是一种非性交的受孕方法，用于治疗 不孕症并怀孕。全世界有多达900万例出生是由于抗逆转录病毒疗法。 未来几年，预计随着更多夫妇推迟生育， 孩子或不孕症的发生更有规律。ART中使用的程序包括复杂的技术， 如体外受精（IVF）和卵胞浆内精子注射，以及不太复杂的程序， 作为配子和胚胎冷冻保存和植入前基因检测。近日，来自各 实验室已经表明ART与母亲和胎儿的健康风险有关， 早产、宫内生长受限、胎盘形成异常和其他妊娠并发症。还有， 最近的研究表明，试管婴儿的后代可能会出现代谢和/或心血管疾病， 在成年期。小鼠模型支持这些临床观察，并表明成年试管婴儿后代 会导致代谢和心血管疾病用于辅助生殖的技术 不断完善，以增加怀孕的成功，但新技术的效果还没有得到改善。 在实施前进行评估。因为生殖系统已经被证明对 子宫内发育期间的扰动可能影响未来的功能，本研究的主要目的是 一项旨在研究IVF程序如何影响小鼠IVF后代生殖系统的正常功能 并阐明所观察结果中涉及的潜在遗传和表观遗传机制。因为 女性和男性有独特的途径和生理功能，他们的生殖系统不能 综合分析，出于这个原因，本提案的目标1将解决形态学，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力 目标2将解决雄性动物的类似终点。确定IVF后代中可能的改变， 生殖系统很重要（1），因为任何用于帮助怀孕程序都应 确保一个健康的孩子，不会发展未来的并发症和（2）因为IVF是常用的， 不孕夫妇潜在的不孕状况可能会传递给后代，最终导致 依赖IVF的后代。该研究金提出的计划将被证明是有益的， 复杂的组织，也用于识别受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良影响。