Animal Sciences Research Center, University of Missouri, Columbia, Missouri, USA.
Laboratory of Animal Breeding and Reproduction, Graduate school of Agriculture, Hokkaido University, Hokkaido, Japan.
Reproduction. 2020 Jun;159(6):757-766. doi: 10.1530/REP-20-0036.
Improving the quality and the developmental competence of in vitro produced (IVP) embryos is an indispensable goal for assisted reproductive technology. Autophagy is a major protective mechanism for intracellular degradation of unnecessary cytoplasmic components. Autophagy ends by the fusion between autophagic vacuoles and lysosomes, allowing the degradation of the cargo by lysosomal enzymes, especially the cathepsins (CTSs). However, it is still unclear how autophagy and cathepsin K (CTSK) relate to embryo development. This study evaluated (1.) the activities of autophagy and CTSK in relation to bovine embryo quality and (2.) the effect of autophagy induction and/or CTSK inhibition on preimplantation embryo development and quality. We show here that good-quality embryos exhibited a greater autophagic activity and less CTSK activity compared to poor-quality embryos. Blastomeres of an individual embryo may vary in their quality. Good quality blastomeres showed an increased autophagic activity and decreased CTSK activity compared to poor-quality blastomeres within the same embryo at different developmental stages. Importantly, induction of autophagy and/or inhibition of CTSK improved the developmental rate (increased blastocyst and hatching rates) and the quality (increased total cell number and decreased the percentage of apoptotic cells) of IVP bovine embryos. These results demonstrate a promising approach to selectively isolate good-quality embryos and improve the efficiency of IVEP of cattle embryos.
提高体外生产(IVP)胚胎的质量和发育能力是辅助生殖技术不可或缺的目标。自噬是细胞内降解不必要的细胞质成分的主要保护机制。自噬通过自噬小泡与溶酶体融合结束,允许溶酶体酶(尤其是组织蛋白酶(CTSs))降解货物。然而,自噬和组织蛋白酶 K(CTSK)与胚胎发育的关系仍不清楚。本研究评估了(1.)自噬和 CTSK 的活性与牛胚胎质量的关系,以及(2.)自噬诱导和/或 CTSK 抑制对植入前胚胎发育和质量的影响。我们在这里表明,与质量差的胚胎相比,优质胚胎表现出更高的自噬活性和更低的 CTSK 活性。单个胚胎的卵裂球可能在质量上存在差异。在不同的发育阶段,与质量差的卵裂球相比,质量好的卵裂球表现出增加的自噬活性和减少的 CTSK 活性。重要的是,自噬的诱导和/或 CTSK 的抑制提高了 IVP 牛胚胎的发育率(增加囊胚和孵化率)和质量(增加总细胞数和减少凋亡细胞的百分比)。这些结果表明,选择性分离优质胚胎和提高 IVEP 牛胚胎效率的方法很有前景。