Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, 1425 Madison Ave., Rm. 14-20A, New York, NY 10029, USA.
FASEB J. 2010 Apr;24(4):1229-38. doi: 10.1096/fj.09-145508. Epub 2009 Dec 9.
A major challenge of assisted reproduction technologies (ARTs) is to mimic the natural environment required to sustain oocyte and embryo survival. Herein, we show that the ceramide-metabolizing enzyme, acid ceramidase (AC), is expressed in human cumulus cells and follicular fluid, essential components of this environment, and that the levels of this enzyme are positively correlated with the quality of human embryos formed in vitro. These observations led us to develop a new approach for oocyte and embryo culture that markedly improved the outcome of in vitro fertilization (IVF). The addition of recombinant AC (rAC) to human and mouse oocyte culture medium maintained their healthy morphology in vitro. Following fertilization, the number of mouse embryos formed in the presence of rAC also was improved (from approximately 40 to 88%), leading to approximately 5-fold more healthy births. To confirm these observations, immature bovine oocytes were matured in vitro and subjected to IVF in the presence of rAC. Significantly more high-grade blastocysts were formed, and the number of morphologically intact, hatched embryos was increased from approximately 24 to 70%. Overall, these data identify AC as an important component of the in vivo oocyte and embryo environment, and provide a novel technology for enhancing the outcome of assisted fertilization. Eliyahu, E., Shtraizent, N., Martinuzzi, K., Barritt, J., He, X., Wei, H., Chaubal, S., Copperman, A. B., Schuchman, E. H. Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization.
辅助生殖技术(ARTs)的主要挑战是模拟维持卵母细胞和胚胎存活所需的自然环境。在此,我们表明,神经酰胺代谢酶,酸性神经酰胺酶(AC),在人卵丘细胞和卵泡液中表达,这是该环境的重要组成部分,并且该酶的水平与体外形成的人类胚胎的质量呈正相关。这些观察结果促使我们开发了一种新的卵母细胞和胚胎培养方法,明显改善了体外受精(IVF)的结果。在人卵和鼠卵培养物中添加重组 AC(rAC)可保持其体外健康形态。受精后,rAC 存在下形成的鼠胚胎数量也得到改善(从大约 40 个增加到 88%),导致健康出生的数量增加了大约 5 倍。为了证实这些观察结果,将不成熟的牛卵母细胞在体外成熟,并在 rAC 存在下进行 IVF。形成的优质胚泡明显增多,形态完整、孵化的胚胎数量从大约 24 个增加到 70 个。总体而言,这些数据表明 AC 是体内卵母细胞和胚胎环境的重要组成部分,并为提高辅助受精的结果提供了一种新的技术。Eliyahu, E., Shtraizent, N., Martinuzzi, K., Barritt, J., He, X., Wei, H., Chaubal, S., Copperman, A. B., Schuchman, E. H. 酸性神经酰胺酶可提高卵母细胞和胚胎的质量,改善体外受精的结果。