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