Yanagimachi Ryuzo
Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology, University of Hawaii Medical School, Honolulu, Hawaii 96822, USA.
Biol Reprod. 2009 Feb;80(2):204-18. doi: 10.1095/biolreprod.108.071993. Epub 2008 Dec 17.
My interest in germ cells began when I first witnessed sea urchin fertilization and embryo development during a laboratory class at Hokkaido University, Sapporo, Japan, almost 60 yr ago. Weismann's concept of germ cells that I learned during my undergraduate years became the driving force of my entire research career. During the early years, my associates and I used mainly the golden hamster and the guinea pig as model animals because their spermatozoa had large acrosomes and we could readily follow changes in the acrosomes without killing or staining spermatozoa. We later used the mouse as our model organism because we wanted to produce live offspring with known genetic backgrounds. A summary of the findings we made during those years includes the following: (1) first in vitro sperm capacitation; (2) discovery of sperm hyperactivation; (3) demonstration of the importance of Ca(2+) in sperm acrosome reaction, hyperactivation, sperm-egg fusion, and egg activation; (4) development of the sperm's fusion competence during the acrosome reaction; (5) characterization of sperm-oviduct relationships before and during fertilization; (6) use of zona-free hamster eggs to examine fertilizing ability and chromosomes of human spermatozoa; (7) development and use of intracytoplasmic sperm injection; (8) use of prespermatozoal cells for the production of offspring; (9) sperm preservation by freeze-drying and freezing whole-animal bodies; and (10) mouse cloning by somatic cell nuclear transfer. My current interests and my visions for the future include the following: (1) mass production of mature eggs and spermatozoa in vitro, (2) permanent sperm preservation at ambient temperature, (3) development of safer and more efficient assisted fertilization (reproduction) technologies, (4) development of safe and efficient methods of cloning, (5) production of artificial organs such as an artificial uterus, (6) development of safe and effective male contraceptives, and (7) prevention of cancer through germ cell research.
大约60年前,我在日本北海道大学札幌分校的一堂实验课上首次目睹海胆受精和胚胎发育过程,从此便对生殖细胞产生了兴趣。我在本科阶段所学的魏斯曼关于生殖细胞的概念,成为了我整个研究生涯的驱动力。在早期,我和我的同事主要使用金黄仓鼠和豚鼠作为模式动物,因为它们的精子有较大的顶体,我们可以在不杀死或染色精子的情况下轻松追踪顶体的变化。后来我们使用小鼠作为模式生物,因为我们想培育出具有已知遗传背景的活体后代。那些年我们的研究发现总结如下:(1)首次实现体外精子获能;(2)发现精子超激活;(3)证明钙离子在精子顶体反应、超激活、精卵融合和卵子激活中的重要性;(4)顶体反应过程中精子融合能力的发展;(5)受精前后精子与输卵管关系的特征描述;(6)使用无透明带仓鼠卵检测人类精子的受精能力和染色体;(7)胞浆内单精子注射技术的开发与应用;(8)利用精子前体细胞培育后代;(9)通过冷冻干燥和冷冻整个动物体来保存精子;(10)通过体细胞核移植进行小鼠克隆。我目前的兴趣和对未来的展望包括:(1)体外大量生产成熟卵子和精子;(2)在常温下永久保存精子;(3)开发更安全、更高效的辅助受精(生殖)技术;(4)开发安全、高效的克隆方法;(5)生产人造子宫等人工器官;(6)开发安全、有效的男性避孕药;(7)通过生殖细胞研究预防癌症。