Department of Internal Medicine, Reproduction and Population Medicine, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
Laboratory for Pharmaceutical Biotechnology, Faculty of Pharmaceutical Science, Ghent University, B-9000 Ghent, Belgium.
Int J Mol Sci. 2023 Mar 31;24(7):6563. doi: 10.3390/ijms24076563.
While human in vitro embryo production is generally performed individually, animal models have shown that culturing embryos in groups improves blastocyst yield and quality. Paracrine embryotrophins could be responsible for this improved embryo development, but their identity remains largely unknown. We hypothesize that supplementation of embryotrophic proteins to a culture medium could be the key to improve individual embryo production. In this study, proteomics screening of culture media conditioned by bovine embryos revealed cathepsin-L as being secreted by both excellent- and good-quality embryos, while being absent in the medium conditioned by poor-quality embryos. The embryotrophic role of cathepsin-L was explored in vitro, whereby bovine zygotes were cultured individually for 8 days with or without cathepsin-L. Preliminary dose-response experiments pointed out 100 ng/mL as the optimal concentration of cathepsin-L in embryo culture medium. Supplementation of cathepsin-L to individual culture systems significantly improved blastocyst development and quality in terms of blastocoel formation at day 7, and the hatching ratio and apoptotic cell ratio at day 8, compared to the control. Taken together, cathepsin-L acts as an important embryotrophin by increasing embryo quality, and regulating blastulation and hatching in bovine in vitro embryo production.
虽然人类体外胚胎生产通常是单独进行的,但动物模型表明,胚胎在群体中培养可以提高囊胚的产量和质量。旁分泌胚胎营养因子可能是导致胚胎发育改善的原因,但它们的身份在很大程度上仍然未知。我们假设向培养基中补充胚胎营养蛋白可能是提高个体胚胎生产的关键。在这项研究中,对牛胚胎条件培养基的蛋白质组学筛选显示组织蛋白酶-L 由优质和良好质量的胚胎分泌,而在劣质胚胎条件培养基中不存在。在体外探索了组织蛋白酶-L 的胚胎营养作用,即用或不用组织蛋白酶-L 将牛受精卵单独培养 8 天。初步的剂量反应实验指出,100ng/ml 是胚胎培养基中组织蛋白酶-L 的最佳浓度。与对照组相比,将组织蛋白酶-L 添加到个体培养系统中,可显著提高囊胚发育和质量,在第 7 天囊胚腔形成方面,以及第 8 天孵化率和凋亡细胞率方面。综上所述,组织蛋白酶-L 通过提高胚胎质量,以及调节牛体外胚胎生产中的囊胚形成和孵化,发挥重要的胚胎营养因子作用。