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小鼠、牛和人类胚胎的可控动态微流控培养可改善发育:概念验证研究。

Controlled Dynamic Microfluidic Culture of Murine, Bovine, and Human Embryos Improves Development: Proof-of-Concept Studies.

作者信息

Alegretti Jose Roberto, Rocha Andre M Da, Nogueira-de-Souza Naiara C, Kato Nobuhiro, Barros Bruna C, Motta Eduardo L A, Serafini Paulo C, Takayama Shuichi, Smith Gary D

机构信息

Huntington-Medicina Reprodutiva, Av Republica do Libano, 529 Ibirapuera, Sao Paulo 04501-000, SP, Brazil.

Department of Gynecology, Federal University of Sao Paulo-UNIFESP, Rua Napoleao de Barros, 715-7°, Sao Paulo 04024-002, SP, Brazil.

出版信息

Cells. 2024 Dec 17;13(24):2080. doi: 10.3390/cells13242080.

Abstract

Classical preimplantation embryo culture is performed in static fluid environments. Whether a dynamic fluid environment, like the fallopian tube, is beneficial for embryo development remains to be determined across mammalian species. Objectives of these proof-of-concept studies were to determine if controllable dynamic microfluidic culture would enhance preimplantation murine, bovine, and human embryo development compared to static culture. This prospective randomized controlled trial tested static versus controlled dynamic culture of preimplantation mouse (n = 397), bovine (n = 242), and human (n = 512) zygotes to blastocyst stages with outcome measures of embryo cleavage, cellular fragmentation, apoptosis, and blastocyst conversion rates. Dynamic culture of mouse and bovine zygotes with microfluidics significantly improved embryo development. Mouse placental imprinted gene expression was significantly different between embryos derived in vivo, by static culture, and by dynamic culture. Using human sibling zygotes, this dynamic microfluidic culture system increased the number of blastomeres per cleavage-stage embryo, reduced cellular fragmentation or apoptosis, improved blastocyst conversion rates, and enhanced blastocyst developmental stages. In conclusion, species-specific longitudinal studies demonstrated that dynamic microfluidic culture significantly improved embryo development, independent of culture media composition, temperature, and gaseous environment. These cellular indicators represent improved embryo development that can translate into higher pregnancy rates in transgenics, domestic livestock and endangered species and treating human infertility.

摘要

经典的植入前胚胎培养是在静态液体环境中进行的。像输卵管那样的动态液体环境是否有利于胚胎发育,在整个哺乳动物物种中仍有待确定。这些概念验证研究的目的是确定与静态培养相比,可控的动态微流控培养是否会促进植入前小鼠、牛和人类胚胎的发育。这项前瞻性随机对照试验对植入前小鼠(n = 397)、牛(n = 242)和人类(n = 512)合子至囊胚阶段进行静态与可控动态培养测试,以胚胎分裂、细胞碎片、细胞凋亡和囊胚转化率作为结果指标。利用微流控技术对小鼠和牛合子进行动态培养显著改善了胚胎发育。在体内、静态培养和动态培养所获得的小鼠胚胎之间,胎盘印记基因表达存在显著差异。使用人类同胞合子,这种动态微流控培养系统增加了每个分裂阶段胚胎的卵裂球数量,减少了细胞碎片或细胞凋亡,提高了囊胚转化率,并提升了囊胚发育阶段。总之,特定物种的纵向研究表明,动态微流控培养显著改善了胚胎发育,这与培养基成分、温度和气态环境无关。这些细胞指标代表了改善的胚胎发育,可转化为转基因动物、家畜和濒危物种更高的妊娠率,以及用于治疗人类不孕症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f506/11674278/8c48e0a04e6e/cells-13-02080-g001.jpg

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