Abstract:
Modulation of phosphoinositide 3-kinase/protein kinase B/phosphatase and tensin homologue (PI3K/AKT/PTEN) pathway in mammals yields mixed results. A deep understanding of its regulation can be a powerful tool for better in vitro blastocyst production. This systematic review aims to map the evidence of PI3K/AKT/PTEN pathway modulation during in vitro maturation (IVM), to assess its effects on meiosis resumption and nuclear maturation progression of mammalian oocytes, and their impacts on embryo development and quality. A total of 1058 articles were screened in three databases, and 22 articles were included. Fifty-two IVM assessments were identified, among which 11 evaluated blastocyst yield. Three PI3K inhibitors (3-methyladenine, Wortmannin, and LY294002) and one AKT inhibitor (SH6) were investigated. The impact of this pathway modulation on meiosis resumption in swines and murines was not well established, depending on the inhibitor used, concentration, and media supplementation, while in bovines, resumption seems to be independent of PI3K/AKT/PTEN pathway. However, progression to metaphase II (MII) is highly controlled by this pathway on both bovines and swines. Studies that focused on the inhibition reversibility showed that the removal of the modulator produced MII rates similar to the control group. Experiments that aimed to temporarily block meiosis resumption or reduce PI3K activity resulted in blastocyst production equal to or even higher than control groups. Altogether, these data indicate the paramount potential of this pathway as a possible strategy to improve overall in vitro embryo production efficiency, by synchronizing both nuclear and cytoplasmic maturation.
摘要:
哺乳动物中磷酸肌醇3-激酶/蛋白激酶B/磷酸酶和张力蛋白同源物(PI3K/AKT/PTEN)途径的调节产生混合结果。对其调节的深刻理解可以成为更好的体外胚泡生产的有力工具。本系统综述旨在绘制体外成熟(IVM)期间PI3K/AKT/PTEN途径调节的证据。评估其对哺乳动物卵母细胞减数分裂恢复和核成熟进程的影响,以及它们对胚胎发育和质量的影响。共筛选了三个数据库中的1058篇文章,包括22篇文章。确定了52项病媒综合防治评估,其中11个评价了胚泡产量。三种PI3K抑制剂(3-甲基腺嘌呤,Wortmannin,和LY294002)和一种AKT抑制剂(SH6)进行了研究。这种途径调节对猪和鼠减数分裂恢复的影响尚未完全确定。根据使用的抑制剂,浓度,和媒体补充,在牛的时候,恢复似乎与PI3K/AKT/PTEN途径无关。然而,向中期II(MII)的进展在牛和猪上都受到该途径的高度控制。专注于抑制可逆性的研究表明,去除调节剂产生的MII率与对照组相似。旨在暂时阻断减数分裂恢复或降低PI3K活性的实验导致胚泡产生等于或甚至高于对照组。总之,这些数据表明,该途径作为提高体外胚胎生产效率的可能策略,具有极其重要的潜力。通过同步核和细胞质成熟。