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张民觉生殖生理学研究
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摘要
在当代世界著名的华裔科学大家的光辉名册中,杨振宁、李政道、丁肇中、李远哲、朱棣文、崔琦、钱永键、陈省身、丘成桐、陶哲轩等,他们或因荣获诺贝尔物理学、化学奖,或因荣获“数学界的诺贝尔奖”——菲尔兹奖、沃尔夫奖,而成为人们耳熟能详和广为传诵的对象。但在世界生理学和医学领域,也有一位同样重要但却被人们包括国人忽视而多少显得有些“落寞”的华裔科学大家,他就是国际生殖生理学大师——张民觉。
     张民觉因其卓越的生殖生理学贡献而被誉为“试管婴儿之父”和“口服避孕药之父”,曾三次荣获诺贝尔奖的提名,是华人在国际生理学和医学领域取得的最高成就者。然而,与以上华裔数学家、物理学家和化学家相比,不仅国人对张民觉的事迹贡献所知甚少,而且国内外迄今尚无关于张民觉科学活动、成就贡献、社会影响的系统、专门和深入的研究,这是极不应该的。
     本论文是国内外首次关于张民觉生殖生理学贡献的全面、专业和深入的研究,是一次大胆而较新的探索。全文围绕张民觉生殖生理学的研究和贡献展开,以时间为主线,客观、真实地再现了其科研历程。主要内容分为六章:
     第一章,介绍了张民觉的求学与科研经历。张民觉在国内三十年的岁月,受到儒家传统文化、家族文化及地域文化的影响,形成了一生的人格品质。中学阶段对生物学的浓厚兴趣是他以后进行生殖生理学研究的主体要素;清华大学接受的良好的系统教育成为他以后科学生涯的基础;国外的求学岁月与科研训练为他成为国际生殖生理学大师铺平了道路。
     第二章,梳理了张民觉精卵生理学基础研究的内容和成就。特别是精子获能、同步化理论的提出,突出了其作为生殖生理学家注重基础理论研究的理念,奠定了20世纪后半叶生殖生理学发展的学理基础。
     第三章,突出了张民觉的精卵受精实验研究。受精是新生命的起点,标志着个体发育的伊始,张民觉是哺乳动物体外受精实验成功的第一人,多种动物卵子的体外受精及其技术上的改进均创始于张民觉的实验室。他凭着顽强毅力和娴熟的技巧,独自完成了几项精卵受精的经典实验,也标志着哺乳动物体外受精技术的成熟。
     第四章,论述了张民觉对人口控制技术的贡献。体外受精技术的成熟及应用催生了试管婴儿的诞生,为不孕夫妇带来了福音。同时,受精和避孕是一个过程的两个方面,据此张民觉又发明了成为节育有效手段的口服避孕药。张民觉的研究成果让不育者能育、能育者节育,为世界人口与社会的发展做出了巨大贡献。
     第五章,阐释了张民觉生殖生理学贡献引发的社会变革。从科学与社会的互动角度阐明了张民觉科学贡献的社会功能以及引发的社会伦理争议。“试管婴儿”的问世,使人类的命运从此由自己主宰;口服避孕药作为人工节育的有效手段,也让妇女从此获得了解放;体外受精技术的成功应用,开辟了畜牧改良的新途径,牛羊遍野不再是遥远的梦。同时,他的科学贡献也引发了医学伦理学、社会学和经济学等多方面的争议。对此,本论文也进行了讨论和分析。
     第六章,凝练出张民觉科学实验成功的启示。在他一生的科学研究生涯中,兴趣是他科学实验成功的原动力,勤奋执着与机遇是科学实验成功的前提,科学方法是他实验成功的保障,而大胆探索、勇于创新是他科学实验成功的关键。即兴趣、勤奋、执着、机遇、方法和创新,是张民觉作为实验科学家之所以成功的“六大法宝”,这当可以引以为当前我国科技创新人才培养的有益借鉴。
     张民觉一生致力于生殖生理学实验研究,他的基础理论和应用研究成果都源于其科学实验,直到去世前仍然可以看到他实验的可贵身影。他一生的科学实验都浓缩在其发表的362篇学术论文之中,是弥足珍贵的科学资料和精神财富。无论是理论上的巨大发现,还是技术上的重大突破,均解决了20世纪生殖生理学发展的瓶颈问题,凸显了他的重要贡献。
     本论文主要采用了文献资料综合分析法、口述科技史方法、结合友邻学科的跨学科研究方法、计量分析的方法、内史和外史相结合的方法,在大量原始英文文献的基础上,系统地发掘总结了张民觉生殖生理学实验成果对生殖生理学的贡献,剖析造就华人生殖生理学家成长的重要因素,总结当今中国培养科技创新人才的某些规律。
     本论文对张民觉这位生殖生理学巨擘的研究历程、生殖生理学成就、科学方法等展开全面发掘,理清了张民觉的成长轨迹和生殖实验成功的路径,总结了张民觉对生殖生理学的伟大贡献。创新之处主要有以下几方面:
     第一,首次较为系统、全面和深刻地探讨了张民觉在生殖生理学基础研究中做出的巨大贡献,填补了国内外对张民觉缺乏系统研究的空白,也进一步丰富了国内对华裔科学家系列的研究。
     第二,诚如一位美国友人曾经所言:“山西有很多寺庙、神佛的塑像,但却很少见科学家的塑像,张民觉博士对世界有巨大贡献,你们应该为他塑一尊像。”2004年在张民觉魂归故里10周年之际,其家乡岚县为张民觉塑了一尊塑像。针对山西以至国内对张民觉了解甚少的状况,本论文对从山西走向世界的科学家进行研究,丰富了山西的科学文化,也充实了山西地方科学史的内容。
     第三,本论文通过对张民觉成长过程中家庭教育、初等教育、高等教育、研究环境等因素的影响分析,旨在揭示从“山里娃”到“天之骄子”嬗变的必要条件,同时也分析了科学实验研究取得成功所必须的科学素质。
     第四,张民觉的科学研究造福了人类,也引发了医学伦理学、社会学、经济学等多学科的争议。本论文从科技与伦理的张力视角,给出了关于张民觉何以三次敲响诺贝尔奖大门而终未能入的社会文化思考。
     第五,透视张民觉成功的因素,探索当今我国科技创新人才培养的新途径。
     本论文力图刻绘出一位立体生动的华裔大科学家的全貌以及他的伟大理念,即他本人所说:科学必将造福于全世界,给人类带来文明。
When we refer to the prominent scientists of Chinese origin in the world, some of them are very familiar, including, Yang Zhen-ning, Zheng-Dao Li, Samuel Chao, Chun Ting, Lee Yuan-tseh, Steve Chu, Cui Qi, Qian Yongjian, Chen Xingshen, Qiu Chengtong, Tao Zhexuan etc. They either won Nobel Prize for Physics or Chemistry, or got the Fields Medal, Wolf Prize for Mathematics, which are called the Nobel Prize for mathematics. In physiology and medical field in the world, there is also an outstanding Chinese origin scientist who is equally important but neglected by Chinese, Chang Min-chueh, the master of international reproductive physiology.
     Chang Min-chueh is considered Father of Tube-baby and Father of Pill, and won the nomination of the Nobel Prize for three times. He is the scientist who makes great achievements in physiology and medical field among Chinese. However, compared with the Chinese origin scientists above, he was seldom heard of in China, and so far there isn't any special and systematical research at home and abroad on the scientific activities, the contributions and the social influence of Chang Min-chueh. It is unfair and shouldn't have been treated like that.
     It is the first time that special and systematical research on reproductive physiology achievements of Chang Min-chueh, which is pioneering. On the basis of the the reproductive physiology researches and contributions of Chang Min-chueh. According to time masterstroke, this thesis represents his scientific research experiences truthfully and objectively. This thesis contains the following six parts:
     Chapter one introduces Chang Min-chueh's experiences of education and scientific researches. Chang Min-chueh was influenced by Confucian traditional culture, family culture and regional culture, which shaped his characters:especially strong interest in biology study at the middle school, which are the essential factors of his reproductive physiology research in the future. Good and systematic education in Tsinghua University provides the foundation for his further science careers. The studying and scientific research training abroad paved the way for him to become the master of international reproductive physiology.
     Chapter two Sorts out Chang Min-chueh's contributions on sperm and egg physiology, and highlights the idea that attaches importance to basic theoretical research as a reproductive physiologist, especially sperm capacitation theory and synchronous theory, which established the academic foundation of reproductive physiology development of late 20th century.
     Chapter three focuses on sperm and egg fertilization experiments research. Fertilization is origin of new life, which symbolizes the beginning of individual development. Chang Min-chueh is the first one who succeeded in in-vitro fertilization of mammal experiment, and the application and its innovation of much mammalian in-vitro fertilization of animals' egg both originates from his lab. He did several classical experiments on sperm-egg fertilization by himself with his perseverance and proficient skills, which also symbolized the technique mature of mammalian in-vitro fertilization.
     Chapter four further discusses the successful application of the in-vitro fertilization technique, especially tube-baby's birth, which brings forth blessings for the couples who either can't give birth or need birth control. Actually, fertilization and contraception are the two sides of one process, by which oral-contraceptive was invented and become the effective means of birth control. Chang Min-chueh's achievements make great contributions for the development of population and society in the world.
     Chapter five illustrates the social function of Chang Min-chueh's scientific contributions from the view of interaction between science and society, and social ethical controversy about them. The birth of tube-baby makes human beings dominate our own fate by ourselves; oral-contraceptive as effective means of artificial contraception also makes women liberated; the successful application of the in-vitro fertilization opens up the new approach to improving livestock husbandry, and flocks and herds graze everywhere will not be a remote dream. At the same time, his scientific contributions bring about many-sided controversy including machine ethics, sociology, and economy etc, which also are discussed in this thesis.
     Chapter six further extracts items resulting in the successful inspiration as a prominent experimental scientist. In his science and research career, interest is the originl power of his successful scientific experiments; diligence, persistence and opportunity are the premise; scientific method is the guarantee. Bold exploration and innovation is the key to his successful scientific experiments. In a short, interest, diligence, persistence, opportunity, method and innovation are Chang Min-chueh's successful "six effective weapons" as an experimental scientist, which can be used for reference to cultivate science and technology innovation talents in our country.
     Chang Min-chueh dedicated his life to the research of reproductive physiology, and both basic theory and application researches are from his scientific experiments. According to his students, they could still see him working in the lab a few weeks before he died. His scientific experiments all his life are condensed in the published 362 academic dissertations, which are regarded as valuable scientific information and spiritual wealth. Whether his great discovery in theory or great breakthroughs on technology, all the findings have resolved the bottleneck problems of reproductive physiology development during 20th century, which reflects his great contributions.
     This thesis takes interdisciplinary research method, computation method, integrate inner-history with extra-history. Based on lots of English documents, it summarizes the contribution of Chang Min-chueh's reproductive physiology experiment achievements in reproductive physiology field, analyses the important factors of his success as a Chinese reproductive physiologist, and sums up some certain regular rules to cultivate science and technology innovation talents in our country.
     This thesis overall explores research experiences, reproductive physiology contributions, scientific methods of Chang Min-chueh as a giant of reproductive physiology field, and make clear the growth track and the way of successful experiments of Chang Min-chueh. It summarizes Chang Min-chueh's great contributions to reproductive physiology. The innovations are mainly the following aspects:
     Firstly, this thesis makes the first systematic, comprehensive and incisive study on Chang Min-Chueh's contributions in the fundamental research of reproductive physiology, fills the blank of the systematical study on Chang Min-Chueh at home and abroad, and further enriches the study on scientists of Chinese origin at home and abroad study.
     Secondly, just as an American friend said:"There are many temples, Buddha statues in Shanxi, but few scientists'statues; Chang Min-Chueh makes a great contribution to the world, so you should make a statue for him." In 2004, it is the 10 anniversary ceremony, and people of his hometown Lan County built a statue for him. As far as the poor recognition to him at home and abroad, this thesis studies the scientists from Shanxi to the world, which enriches Shanxi scientific culture, and fulfill she content of Shanxi local history of science and technology.
     Thirdly, starting from the influential items analysis on Chang Min-Chueh's family background, primary education, secondary education, and research environment, it aims to discover the necessary conditions of changing from "a kid in countryside" to "a specially privileged person". Meanwhile, it also analyzes the necessary scientific qualities of successful scientific experiments.
     Fourthly, Chang Min-chueh's scientific research made benefit for human beings, but it also led to medical ethics, sociology, economics and other subjects of controversy. From the tension of technology and ethics perspective, this thesis gave the public social and cultural thinking of how Chang Min-chueh was nominated the Nobel Prize three times and finally not accepted.
     Fifthly, this thesis discusses the essence of Chang Min-Chueh's successful factors and explores new ways of scientific innovation talents training in today's China.
     This thesis seeks to carve out a vivid three-dimensional great Chinese origin scientist picture, and his great idea:Science will benefit the whole world, and bring civilization to mankind.
引文
① M. C. Chang and A. Walton. The effects of low temperature and acclimatization on the respiratory activity and survival of ram spermatozoa [J]. Proc. Royal Soc. Series B,1940(129):517-527.
    ① M. C. Chang. Development and fate of transferred rabbit ova or blasocysts in relation to the ovulation time of recipients [J]. J. Exp. Zool.,1950(114):197-226.
    ①赵志忠.试管婴儿之父——张民觉[M].远方出版社,2004年,3-13.
    ① K.S.Lashley(1890-1958),为美国著名行为主义心理学家,一生主要从事研究动物脑的机能与行为的关系问题。
    ②赵志忠.试管婴儿之父——张民觉[M].远方出版社,2004年,27.
    ③ M. C. Chang. A formal-thionon method for the fixation and staining of never cells and fiber tracts[J]. Anat. Rec.,1936(65):437-441.
    ①林宝发.张民觉、杨祥发同被选为美国家科学院院士[N].参考消息,1990-05-05.
    ②赵志忠.试管婴儿之父——张民觉[M].远方出版社,2004年,28.
    ③赵志忠.试管婴儿之父——张民觉[M].远方出版社,2004年,27.
    ①王进.试管婴儿之父——张民觉[J].观察,2004-10-19.
    ① M. C. Chang. Recollections of 40Years at The Worcester Foundation for Experimental Biology[J]. The Physiologist,1985(128).
    ② M.C. Chang. Recollections of 40Years at The Worcester Foundation for Experimental Biology[M].The Physiologist,1985(128).
    ① M. C. Chang and A. Walton The effects of low temperature and acclimatization on the respiratory activity and survival of ram spermatozoa[J]. Proc. Royal Soc. Series B,1940(129):517-527.
    ① M. C. Chang. Recollections of 40Years at The Worcester Foundation for Experimental Biology[J]. The Physiologist,1985(128).
    ② M.C. Chang. Recollections of 40Years at The Worcester Foundation for Experimental Biology[J]. The Physiologist,1985(128).
    ①林宝发.张民觉、杨祥发同被选为美国国家科学院院士[N].参考消息,1990-05-05.
    ① M. C. Chang. Experimental Studies of Mammalian Spermatozoa and Eggs[J]. Biology of Reproduction, 1971(4):3-15.
    ② M. C. Chang. Effects of oestrogen (stilboestrol) on the sperm production of adult rams[J]. J. Endocrinol,1942(3):192-202.
    ③ M.C. Chang. The sperm production of adult rams in relation to frequency of semen collection[J]. J. Agric. Sci.,1946(35):243-246.
    ①周宗瑶综述、王一飞指导.附睾精子成熟功能研究进展[J].生殖与避孕,2003(4):238-243.
    ②王一飞.人类生殖生物学[M].上海科学技术文献出版社,2005年,67.
    ③ M. C. Chang and A. Walton. The effects of low temperature and acclimatization on the respiratory activity and survival of ram spermatozoa[J]. Proc. Royal Soc. Series B,1940(129):517-527.
    ④ M. C. Chang. Dis integration of epididymal spermatozoa by application of ice to the scrotal testis[J]. J. Exp. Biol.,1943(20):16-22.
    ① M. C. Chang. Fertilizing capacity of spermatozoa following cold treatment of the scrotal testes of rabbits[J]. J. Exp. Biol.,1946(22):95-100.
    ①M.C. Chang. Fertilizing life of ferret sperm in the female track[J]. J. Exp. Zool.1965(158):87-100
    ② Dott, H.M. and M. C. Chang. Fertilizing life of ejaculated and epididymal rabbit sperm in the female tract [J]. Anat. Rec.,1968(154):459. (abstract)
    ③ McGaughey, R. W., J. H. Marston and M. C. Chang. Fertilizing life of mouse spermatozoa in the female tract[J]. J. Reprod. Fert.1968(16):147-150.
    ① M. C. Chang. Dorothy M. Hunt and C. L. Turbyfill. High resistance of Mongolian gerbils to irradiation[J]. Nature,1964(203):536-537.
    ② C. L. Turbyfill. and M. C. Chang. Effects of X-irradiation of immature hamsters on growth and development of gonads[J]. Anat. Rec.,1969(163):353-358.
    ① M. C. Chang and G. Pincus. Physiology of fertilization in mammals[J]. Physiol. Reviews,1951 (31):1026.
    ②张燕林.略述张民觉先生在生殖生理学上的卓越贡献.岚县文史资料,1987(2).
    ③M.C. Chang. Fertilizing capacity of sperm deposited in the fallopian tube[J]. Nature,1951 (168):697.
    ①M. C. Chang. Experimental Studies of Mammalian Spermatozoa and Eggs. Biology of Reproduction[J]. 1971 (4):3-15.
    ① M.C. Chang. Development of fertilizing capacity of rabbit spermatozoa in the uterus[J]. Nature, 1955 (175):1036.
    ② M. C. Chang and Diane Sheaffer. Number of spermatozoa ejaculated at copulation, transported into the female tract, and present in the male tract of the golden hamster[J]. J. Heredity,1957(68):107-109.
    ③ M.C. Chang. Capacitation of rabbit spermatozoa in the Fallopian tube and in the uterus [J]. J. Exp. Zool,1962(151):159-166.
    ④ M.C. Chang. A detrimental effect of seminal plasma on the fertilizing capacity of sperm[J]. Nature, 1957(179):258-259.
    ⑤ M.C. Chang and Thorsteinn Thorsteinsson. Effects of urine on motility and fertilizing capacity of rabbit spermatozoa[J]. Fert. and Steril,1958(9):231-237.
    ⑥ M.C. Chang. Effects of osmotic pressure and hydrogen-ion concentration on the motility and fertilizing capacity of rabbit spermatozoa[J]. Fert. and Steril.,1958(9):510-520.
    ① M. C. Chang. Capacitation of rabbit spermatozoa in the uterus with special reference to the reproductive phases of the female[J]. Endocrinology,1958(63):619-628.
    ② M. C. Chang. Capacitation of rabbit spermatozoa in the uterus with special reference to the reproductive phases of the female[J]. Endocrinology,1958(63):619-628.
    ① M. C. Chang and D M. Hunt. Effects of various progestins and estrogens on the gamete transport and fertilization in the rabbit[J]. Fert, Steril.,1970(21):683-686.
    ② M.C. Chang and Anna L. Southam. The fertilizing life of spermatozoa in the female tract of rabbits and ferrets treated with oestrogen [J]. J. Reprod. Fert.,1970(23):173-175.
    ① M.C. Chang. Hormonal regulation of sperm capacitation in Biosciences 4, Schering Symposium on, Mechanisms Involved in Conception[J], Berlin, Ed. Gerhard Raspe,. Pergamon Press., (1969)p.14-24.
    ① Iwamatsu, T. and M. C. Chang. Capacitation of hamster spermatozoa treated with rabbit tubal fluid or rabbit and bovine tubal cystic fluids[J]. J. Exp. Zool.,1972(182):211-216.
    ② Toyoda, Y. and M. C. Chang. Capacitation of epididymal spermatozoa in a medium with high K/Na ratio and cyclic AMP for the fertilization of rat eggs in vitro[J]. J. Reprod. Fert.,1974(36):125-134.
    ③M. C. Chang. Effect of pretreatment of rat spermatozoa with high concentrations of Nacl on sperm capacitation and fertilization of eggs in vitro[J]. Biol. Reprod.,1975(13):187-189.
    ① M. C. Chang. Penetration of hamster and rabbit zona-free eggs by rat and mouse spermatozoa with special reference to sperm capacitation[J]. J. Reprod. Fert.,1976(46):239-241.
    ②张燕林.略述张民觉先生在生殖生理学上的卓越贡献.岚县文史资料,1987(2)
    ② M. C. Chang. The meaning if sperm capacitation. A historical perspective[J]. J. Andrology, 1984(5):45-50
    ① M. C. Chang. The meaning if sperm capacitation. A historical perspective[J]. J. Andrology, 1984(5):45-50.
    ① M. C. Chang. Experimental Studies of Mammalian Spermatozoa and Eggs[J]. Biology of Reproduction, 1971(4):3-15.
    ② M. C. Chang. The meaning if sperm capacitation. A historical perspective[J]. J. Andrology, 1984(5):45-50.
    ③ Beford, J. M. and M. C. Chang. Removal of decapacitation factor from seminal plasma by high centrifugation[J]. Amer. J. Physiol,1962 (202):179-181.
    ①张燕林.略述张民觉先生在生殖生理学上的卓越贡献.岚县文史资料,1987(2).
    ②卵子赠送和不育妇女的卵巢组织冷冻[J].生殖医学杂志,2004(6):329.
    ③ M. C. Chang. Normal development of fertilized rabbit ova stored at low temperature for several days[J]. Nature,1947(159):602.
    ① M. C. Chang. Transplantation of fertilized rabbit ova:the effect on viability of age, in vitro storage period, and storage temperature[J]. Nature,1949(161):978.
    ② Marden, W. G. R. and M. C. Chang. The aerial transport of mammalian ova for transplantation [J]. Science, 1952(115):705-262.
    ③ M. C. Chang. Storage of unfertilized rabbit ova:subsequent fertilization and the probability of normal development [J]. Nature,1953(172):353.
    ① Yanagimachi, R. and M. C. Chang. Fertilizable life of the dolden hamster ova and the cortical change at the time of losing fertilizability[J]. Anat. Rec.,1962(142):334.
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    56. M.C. Chang. Dis-integration of epididymal spermatozoa by application of ice to the scrotal testis [J]. J. Exp. Biol.,1943(20):16-22.
    57. M.C. Chang. Fertilizing capacity of spermatozoa following cold treatment of the scrotal testes of rabbits [J]. J. Exp. Biol.,1946(22):95-100.
    58. M.C. Chang and A. Walton. The effects of low temperature and acclimatization on the respiratory activity and survival of ram spermatozoa [J]. Proc. Royal Soc. Series B, 1940(129):517-527.
    59. M.C. Chang. Fertilizing life of ferret sperm in the female track [J]. J. Exp. Zool., 1965(158):87-100
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    61. McGaughey, R.W., J.H. Marston and M.C. Chang. Fertilizing life of mouse spermatozoa in the female tract [J]. J. Reprod. Fert.,1968(16):147-150.
    62. M.C. Chang and D M. Hunt. Effects of various progestins and estrogens on the gamete transport and fertilization in the rabbit [J]. Fert, Steril.,1970(21):683-686.
    63. M.C. Chang and Anna L. Southam. The fertilizing life of spermatozoa in the female tract of rabbits and ferrets treated with oestrogen [J]. J. Reprod. Fert., 1970(23):173-175.
    64. M.C. Chang, Dorothy M. Hunt and E.B. Romanoff. Effects of radiocobalt irradiation of rabbit spermatozoa in vitro on fertilization and early development [J]. Anat. Rec.,1957(129):211-230.
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    66. M.C. Chang and D.M. Hunt Lethal. Effects of gamma radiation in the ferret [J]. Fed. Proc.,1959(18):25.
    67. Mounib, M.S. and M.C. Chang. The effects of ionizing radiation on sperm metabolism [J]. Fed. Proc.,1963(22):570.
    68. Mounib, M.S. and M.C. Chang. Effects of irradiation on the metabolism of spermatozoa [J]. Radiation Research,1964(22):144-154.
    69. Marden, W.G.R. and M.C. Chang. The aerial transport of mammalian ova for transplantation [J]. Science,1952(115):705-262.
    70. M.C. Chang, Dorothy M.Hunt and C.L. Turbyfill. High resistance of Mongolian gerbils to irradiation [J]. Nature,1964(203):536-537.
    71. Dott, H.M.K. Ishida and M.C. Chang. The effect of X-irradiation of rabbit spermatozoa in vitro in different gases on egg development and sperm dehydrogenases [J]. J. Reprod. Fert.,1966(11):485-487.
    72. M.C. Chang, Dorothy M.Hunt. and C.L. Turbyfill. Fertilization and early development after radiocobalt irradiation of rabbit oocytes and sperm in the female tract [J]. Anat. Rec.,1966(154):713-726.
    73. C.L. Turbyfill. and M.C. Chang. Effects of X-irradiation of immature hamsters on growth and development of gonads [J]. Anat. Rec.,1969(163):353-358.
    74. R.W. McGaughey and M.C. Chang. Initial chromosomal lesions induced by X-irradiating primary spermatocytes of mice [J]. Can. J. Genet. Cytol,1973(15):341-348.
    75. M.C. Chang and James J. Mcdonough. An experiment to cross the cottontail and the domestic rabbit [J]. J. of Heredity,1955(46):41-44.
    76. M.C. Chang, J.H. Marston and Dorothy M. Hunt. Reciprocal fertilization between the domesticated rabbit and the snowshoe hare with special reference to insemination of rabbits with an equal number of hare and rabbit spermatozoa [J]. J. Exp. Zool.,1964(155): 437-446.
    77. M.C. Chang. Implantation of ferret ova fertilized by mink sperm [J]. J. Exp. Zool., 1965(160):67-80.
    78. M.C. Chang. Artificial insemination if snowshoe hares (lepus Americanus) and the transfer of their fertilized eggs to the rabbit (Oryctologus cuniculus) [J]. J. Reprod. Fertil.,1965(10):447-449.
    79. J.H. Marston. and M.C. Chang. The morphology and timing of fertilization and early cleavage in the Mongolian gerbil and deer mouse [J]. J. Embryol. Exp. Morph., 1966(15):169-191.
    80. M.C. Chang. Reciprocal insemination and egg transfer between ferrets and mink [J]. J. Exp. Zool.,1968(168):49-59.
    81. M.C. Chang, Dorothy M. Hunt. and J.H. Marston. The capacitation time and fertilizing life of snowshoe hare spermatozoa in the female tract of the rabbit [J]. J. Reprod. Fert.,1971(25):287-289.
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    83. M.C. Chang. Fertilizing capacity of sperm deposited in the fallopian tube [J]. Nature,1951(168):697.
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    86. M.C. Chang and Diane Sheaffer. Number of spermatozoa ejaculated at copulation, transported into the female tract, and present in the male tract of the golden hamster [J]. J.Heredity,1957(68):107-109.
    87. M.C. Chang. Capacitation of rabbit spermatozoa in the Fallopian tube and in the uterus [J]. J. Exp. Zool,1962(151):159-166.
    88. M.C. Chang. A detrimental effect of seminal plasma on the fertilizing capacity of sperm [J]. Nature,1957(179):258-259.
    89. M.C. Chang and Thorsteinn Thorsteinsson. Effects of urine on motility and fertilizing capacity of rabbit spermatozoa [J]. Fert. and Steril,1958(9):231-237.
    90. M.C. Chang. Effects of osmotic pressure and hydrogen-ion concentration on the motility and fertilizing capacity of rabbit spermatozoa [J]. Fert. and Steril.,1958(9): 510-520.
    91. M.C. Chang. Capacitation of rabbit spermatozoa in the uterus with special reference to the reproductive phases of the female [J]. Endocrinology,1958(63):619-628.
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    93. M.C. Chang. Capacitation of rabbit spermatozoa in the uterus with special reference to the reproductive phases of the female [J]. Endocrinology,1958(63):619-628.
    94. Iwamatsu, T. and M.C. Chang. Capacitation of hamster spermatozoa treated with rabbit tubal fluid or rabbit and bovine tubal cystic fluids [J]. J. Exp. Zool., 1972(182):211-216.
    95. Toyoda, Y. and M.C. Chang. Capacitation of epididymal spermatozoa in a medium with high K/Na ratio and cyclic AMP for the fertilization of rat eggs in vitro [J]. J. Reprod. Fert.,1974(36):125-134.
    96. M.C. Chang. Effect of pretreatment of rat spermatozoa with high concentrations of Nacl on sperm capacitation and fertilization of eggs in vitro [J]. Biol. Reprod, 1975(13):187-189.
    97. Iwamatsu, T. and M.C. Chang. Further investigation of capacitation of sperm and fertilization of mouse eggs in vitro [J]. J. Exp. Zool,1970(175):271-282.
    98. M.C. Chang. Capacitation of spermatozoa and fertilization of mammalian eggs [J]. Morph. Aspects of Andrology,1970(1):80-83.
    99. M.C. Chang, Dorothy M. Hunt. and J.H. Marston. The capacitation time and fertilizing life of snowshoe hare spermatozoa in the female tract of the rabbit [J]. J. Reprod. Fert,1971(25):287-289.
    100. Miyamoto, H. and M.C. Chang. The importance of serum albumin and metabolic intermediates for capacitation of spermatozoa and fertilization of mouse eggs in vitro [J]. J. Reprod. Fert.,1972(32):193-205.
    101. Niwa, K. and M.C. Chang. Effects of sperm concentration on the capacitation of rat spermatozoa [J]. J. Exp. Zool.,1974(189):353-356.
    102. M.C. Chang and R.H.F. Hunter. Capacitation of mammalian sperm:Biological and experimental aspects [M]. Handbook of Physiology, Endocrinology V, Chapter 16, 1975:pp.339-351.
    103. M.C. Chang. Requirement of capacitation for sperm penetration of zona-free rat eggs [J]. J. Reprod. Fertil.,1975(44):305-308.
    104. M.C. Chang. Penetration of hamster and rabbit zona-free eggs by rat and mouse spermatozoa with special reference to sperm capacitation [J]. J. Reprod. Fertil., 1976(46):239-241.
    105. M.C. Chang. Experimental Studies of Mammalian Spermatozoa and Eggs [J]. Biology of Reproduction,1971(4):3-15.
    106. M.C. Chang. The meaning if sperm capacitation:a historical perspective [J]. J. Andrology,1984(5):45-50.
    107. Beford, J.M. and M.C. Chang. Removal of de-capacitation factor from seminal plasma by high centrifugation [J]. Amer. J. Physiol,1962(202):179-181.
    108. M.C. Chang. Fertilizing Capacity of Sperma deposited into the Fallopian Tubes [J]. Nature,1951(168):697.
    109. M.C. Chang. Second Annual Carl G. Hartman Lecture:Experimental Studies of Mammalian Spermatozoa and Eggs [J]. Biology of Reproduction,1971(4):3-15.
    110. M.C. Chang. Implantation of ferret ova fertilized by mink sperm [J]. J. Exp. Zool.,1965(160):67-80.
    111. M.C. Chang. Reciprocal transplantation of eggs between rabbit and ferret [J]. J. Exp. Zool.,1966(161):297-305.
    112. M.C. Chang, J.H. Casas and Dorothy M. Hunt. Development of ferret eggs after 2 to 3 day in the rabbit Fallopian tube [J]. J. Reprod. Fert.,1971(25):129-131.
    113. Wu, J.T. and M.C. Chang. Reciprocal fertilization between the ferret and short-tailed weasel with special reference to the development of ferret eggs fertilized by weasel sperm [J]. J. Exp. Zool.,1973(183):281-290.
    114. Fukuda, Y. M.B. Maddock and M.C. Chang. In vitro fertilization of two species of deer mouse eggs by homologous or heterologous sperm and penetration of laboratory mouse eggs by deer mouse sperm [J]. J. Exp. Zool.,1979(207):129-133.
    115. M.C. Chang. Normal development of fertilized rabbit ova stored at low temperature for several days [J]. Nature,1947(159):602.
    116. M.C. Chang. The effects of low temperature on fertilized rabbit ova in vitro and the normal development of ova kept at low temperature for several days [J]. J. Gen. Physiol.,1948(31):385-410.
    117. M.C. Chang. Storage of unfertilized rabbit ova:subsequent fertilization and the probability of normal development [J]. Nature,1953(172):353.
    118. M.C. Chang. Resumption of heartbeat in the rabbit embryo after exposure to low temperature [J]. Science,1953(118):550-552.
    119. M.C. Chang. Development of parthenogenetic rabbit blastocysts induced by low temperature storage of unfertilized ova [J]. J. Exp. Zool.,1954(125):127-149.
    120. Parkening, T.A., and M.C. Chang. Effects of various low temperatures, cryoprotective agents and cooling rates on the survival, fertilizability and development of frozen-thawed mouse eggs [J]. J. Exp. Zool.,1976(197):369-374.
    121. Parkening, T.A. and M.C. Chang. Effects of cooling rates and maturity of the animal on the recovery and fertilization of frozen-thawed rodent eggs [J]. Biol. Reprod., 1977(17):527-531.
    122. Kasai, M.A Iritani and M.C. Chang. Fertilization in vitro of rat ovaeian oocytes after freeing and thawing [J]. Biol. Reprod.,1979(21):839-844.
    123. M.C. Chang. Probability of normal development after transplantation of fertilization in the rabbit ova stored at different temperatures [J]. Proc. Soc. Exp. Biol. and Med.,1948(68):680-683.
    124. M.C. Chang. Transplantation of fertilized rabbit ova:the effect on viability of age, in vitro storage period, and storage temperature [J]. Nature,1949(161):978.
    125. M.C.Chang and G. Pincus. Artificial insemination of rabbits and transplantation of rabbit eggs [J]. Fed. Proc.,1949 (8):(Abstract).
    126. M.C. Chang. Fertilizability of rabbit ova and the effects of temperature in vitro on their subsequent fertilization and activation in vivo [J]. J. Exp. Zool., 1952(121):351-382.
    127. M.C. Chang and L.Fenandez-Cano. Effects of short changes of environmental temperature and low atmospheric pressure on the ovulation if rats [J]. Amer. J. of Physiol., 1959(196):131-165.
    128. M.C. Chang, D.M. Hunt and E.B. Romanoff. Irradiation of rabbit spermatozoa and ova in vitro [J]. Anat. Rec.,1957(127):275.
    129. M.C. Chang, Dorothy M. Hunt and E.B. Romanoff. Effects of radiocobalt irradiation of unfertilized or fertilized rabbit ova in vitro on subsequent fertilization and development in vivo [J]. Anat. Rec.,1958(132):161-180.
    130. M.C. Chang and D.M. Hunt. Effects of in vitro radiocobalt irradiation of rabbit ova on subsequent development in vivo with special reference to the irradiation of maternal organism [J]. Anat. Rec.,1960(137):511-520.
    131. Harvey, E.B., and M.C. Chang. Effects of X-irradiation of ovarian ova of the golden hamsters [J]. Anat. Rec.,1962(142):239.
    132. M.C. Chang. Effects of X-irradiation of ovarian ova on the morphology of fertilized ova and development of embryos [J]. J.Cell and Comp. Physiol.,1963(61): 133-144.
    133. Harvey, E.B., and M.C. Chang. Effects of single and fractionated irradiation on the embryonic development of the hamster [J]. J. Cell and Comp. Physiol., 1964(64):445-454.
    134. M.C. Chang. The effects of X-irradiation of the rat ovary on implantation and embryonic development [J]. Biol. Reprod.,1973(9):343-349.
    135. G. Pincus and M.C. Chang. The effects of progesterone and related compounds on ovulation and early development in the rabbit [J]. Acta Physiol. Latino., 1953(3):177-183.
    136. Mounib, M.S. and M.C. Chang. Metabolism of glucose, fructose and pyruvate in the 6-day rabbit blastocyst [J]. Exp. Cell Res.,1965(38):201-215.
    137. Ishida, K. and M.C. Chang. Histochemical demonstration of succinic dehydrogenase in hamster and rabbit eggs [J]. J.of Histochem. And Cytochem., 1965(13):470-475.
    138. M.C. Chang. Transport of eggs from the fallopian tube to the uterus as a function of oestrogen [J]. Nature,1966(212):1048-1049.
    139. Toyda, Y. and M.C. Chang. Sperm penetration of rat eggs in vitro after dissolution of zona pellucida by Chymotrypsin [J]. Nature,1968(220):589-591.
    140. M.C. Chang. Fertilization, transportation and degeneration of eggs in pseudopregnant or progesterone-treated rabbits[J]. Endocrinology,1969 (84):356-361.
    141. Wu, J.T. and M.C. Chang. Effects of progesterone and estrogen on the fate of blastocysts in ovarietomiaed pregnant ferrets:Apreliminary study [J]. Biol. Reprod., 1972(7):231-237.
    142. Harvey, E.B., R. Yanagimachi and M.C. Chang. Onset of estrus and ovulation in the golden hamster [J]. J. Exp. Zool.,1961(146):231-236.
    143. Yanagimachi, R. and M.C. Chang. Fertilizable life of golden hamster ova and their morphological changes at the time of losing fertilizability[J]. J. Exp. Zool., 1961(148):185-204.
    144. Yanagimachi, R. and M.C. Chang. Number of leucocytes in the uterus of hamster during estrous cycle and following mating [J]. Fed. Proc.,1962(21):437.
    145. Yanagimachi, R. and M.C. Chang. Fertilizable life of the golden hamster ova and the cortical change at the time of losing fertilizability [J]. Anat. Rec.,1962(142):334.
    146. Harvey, E.B., and M.C. Chang. Effects of single and fractionated X-irradiation of ovarian ova on embryonic development of the hamster [J]. J. Cell and Comp. Physiol., 1964(63):183-188.
    147. J.H. Marston., Yanagimachi, R. and M.C. Chang. The morphology of the first cleavage division in the mouse, Mongolian gerbil, golden hamster and rabbit [J]. Anat. Rec.,1964(148):417(Abstract)
    148. Dorothy M.Hunt. and M.C. Chang. Fertilization and cleavage of guinea pig ova [J]. Anat. Rec.,1964(148):417 (Abstract)
    149. J.H. Marston. and M.C. Chang. The time of ovulation, fertilization and cleavage in the Mongolian gerbil (Meriones unguiculatus) [J]. Anat. Rec.,1964(148):387. (Abstract).
    150. M.C. Chang. Effects of heterologous sera on fertilized rabbit ova [J]. J.Gen.Physiol.,1949(32):291-300.
    151. M.C. Chang. The effects of blood serum and seminal plasma on the mammalian spermatozoa and eggs [M]. Union Internationale des sciences Biologiques. Series B., 1949(3):23-25.
    152. M.C. Chang. The effect of seminal plasma on fertilized rabbit ova [J]. Proc. Nat. Academy of Sci.,1950(36):188-191.
    153. M.C. Chang. The maturation of rabbit oocytes in culture and their maturation, activation, fertilization and subsequent development in the Fallopian tubes [J]. J. Exp. Zool.,1955(128):379-406.
    154. M.C. Chang. Development and fate of transferred rabbit ova or blasocysts in relation to the ovulation time of recipients [J]. J. Exp. Zool.,1950(114):197-226.
    155. Yanagimachi, R. and M.C. Chang. Fertilization of the golden hamster ova following post-coital ligation of the oviduct [J]. Anat. Rec.,1963(145):303.
    156. StellaPickworth, G. Yerganian and M.C. Chang. Fertilization and early development in the Chinese hamster, Cricetulus griseus [J]. Anat. Rec.,1968 (162):197-208.
    157. Pickworth, Stella and M.C. Chang. Fertilization of Chinese hamster eggs in vitro [J]. J. Reprod. Fert.,1969 (19):371-374.
    158. Iwamatsu, T. and M.C. Chang. In-vitro fertilization of mouse eggs in the presence of bovine follicular fluid [J]. Nature,1969 (224):919-920.
    159. Iwamatsu, T. and M.C. Chang. Factors involved in the fertilization of mouse eggs in vitro [J]. J. Reprod. Fert.,1971(26):197-208.
    160. Miyamoto, H. and M.C. Chang. Fertilization of rat eggs in vitro [J]. Biol. Reprod.,1973 (9):384-393.
    161. Toyoda, Y. and M.C. Chang. Fertilization of rat eggs in vitro by epididymal spermatozoa and development of eggs following transfer [J]. J. Reprod. Fert.,1973 (36):9-22.
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    163. Niwa, K. and Miyamoto, H. and M.C. Chang. Fertilization in vitro of rat eggs as affected by the maturity of the females and the sperm concentration [J]. J. Reprod. Fert., 1973(33):577-580.
    164. Niwa, K. and M.C. Chang. Optimal sperm concentration and minimal number of spermatozoa for fertilization in vitro of rat eggs [J]. J. Reprod. Fert.,1974(40):471-474.
    165. Niwa, K. and M.C. Chang. Fertilization of rat eggs in vitro at various times before and after ovulation with special reference to fertilization of ovarian oocytes matured in culture [J]. J. Reprod. Fert.,1975(43):435-451.
    166. M.C. Chang. Fertilization of rabbit ova in vitro [J].Nature,1959(184):466-467.
    167. Toyoda, Y. and M.C. Chang. Capacitation of epididymal spermatozoa in a medium with high K/Na ratio and cyclic AMP for the fertilization of rat eggs in vitro [J]. J. Reprod. Fert.,1974(36):125-134.
    168. Miyamoto, H., Toyoda, Y. and M.C. Chang. Effect of hydrogen-ion concentration on in vitro fertilization of mouse, golden hamster and rat eggs [J]. Biol. Reprod.,1974(10):487-493.
    169. M.C. Chang. In vivo and in vitro fertilization of hamster, rat and mouse eggs after treatment with anti-hamster ovary antiserum [J]. J. Exp. Zool.,1976(195):409-416.
    170. M.C. Chang. Effect of anti-rat ovary antiserum on the fertilization of rat, mouse and hamster eggs in vivo and in vitro [J]. Biol. Reprod.,1976(14):354-361.
    171. M.C. Chang. The effect of passive immunization with hetero and isoimmune anti-ovary antiserum on the fertilization of mouse, rat and hamster eggs [J]. Biol. Reprod., 1976(15):361-365.
    172. M.C. Chang. Further studies of antisera on the fertilization of mouse, rat, and hamster eggs in vivo and in vitro [J]. Int. J. of Fertil.,1977(22):129-139.
    173. Harker, M.J.K., R.C. Skarnes, M.C. Chang and R.W. McGaughey. Effects of antilymphocytic serum (ALS) on pregnancy in rodents [J]. Biol.Reprod., 1970(2):335-345.
    174. M.C. Chang. A detrimental effect of seminal plasma on the fertilizing capacity of sperm [J]. Nature,1957(179):258-259.
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    176. M.C.Chang and G. Pincus. Physiology of fertilization in mammals [J]. Physiological Reviews,1951(31):10-26.
    177. Pincus G. and M.C. Chang. The effects of progesterone and related compounds on ovulation and early development in the rabbit [J]. Acta Physiol. Latino, 1953(3):177-183.
    178. M.C. Chang. Effects of oestrogen (stilboestrol) on the sperm production of adult ram [J].J. Endocrinol.,1942(3):192-202.
    179. Pincus G. and M.C. Chang. The effects of progesterone and related compounds on ovulation and early development in the rabbit [J]. Acta Physiol. Latino., 1953(3):177-183.
    180. Slechta, Robert F., M.C. Chang. and G. Pincus. Effects of progesterone and related compounds on mating and pregnancy in the rat [J]. Fert. and Ster., 1954(5):282-293.
    181. Pincus, Gregory, M.C. Chang, E.S.E.Hafez, M.X.Zarrow and Anne Merrill. Effects of certain 19-nor steroids on reproductive processes in animals [J]. Science, 1956(124):890-891.
    182. Pincus, Gregory, John Rock, M.C. Chang and C.R. Garcia. Effects of certain 19-nor steroids on reproductive processes and fertility [J]. Fed.Proc.,1959(18):1051.
    183. M.C. Chang. Degeneration of ova in the rat and rabbit following oral administration of 1-(p-2diethylamino-ethoxyphenyl)-1-phenyl-2-anisylethanol [J]. Endocrinology,1959(65):339-342.
    184. M.C. Chang. Effects of certain antifertility agents on the development of rabbit ova [J]. Fert. and Steril.,1964(15):97-106.
    185. M.C. Chang and Yanagimachi, R. Effects of estrogens and other compounds as oral antifertility agents on the development of rabbit ova and hamster embryos [J]. Fert. and Ster.,1965(16):281-291.
    186. M.C. Chang and M.J.K. Harper. Effects of ethinyl estradiol on egg transport and development and spermatozoa in the rabbit [J].Endocrinology,1966(78):860-872.
    187. M.C. Chang. Effects of progesterone and related compounds on fertilization, transportation and development of rabbit eggs [J].Endocrinology,1967(81):1251-1260.
    188. Casas, J.H. and M.C. Chang. Effects of subcutaneous implantation or intrauterin insertion of silastic tube containing steroids on the fertility of rats [J]. Biol. Reprod., 1970(2):315-325.
    189. M.C. Chang, J.H. Casas and Dorothy M.hunt. Prevention of pregnancy in the rabbit by subcutaneous implantation of silastic tube containing oestrogen [J]. Nature, 1970(226):1262-1263.
    190. M.C.Chang and M.J.K. Harper. Effects of ethinyl estradiol on egg transport and development and spermatozoa in the rabbit [J]. Endocrinology,1966(78):860-872.
    191. M.C. Chang. Effects of oral administration of medroxy-prodesterone acetate and ethinyl estradiol on the transportation and development of rabbit eggs [J]. Endocrinology, 1966(79):939-948.
    192. M.C. Chang. Transport of eggs from the fallopian tube to the uterus as a function of oestrogen [J]. Nature,1966 (212):1048-1049.
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    199. Casas, J.H. and M.C. Chang. Effects of subcutaneous implantation or intrauterine insertion of silastic tube containing steroid on the fertility of rats [J]. Biol. Reprod.,1970(2):315-325.
    200. M.C. Chang. Antifertility activity of 3-Chloro-1,2-propanediol (U-5897) on male rats [J]. Biol. Reprod.,1970(2):299-304.
    201. M.C. Chang. Development and fate of transferred rabbit ova or blasocysts in relation to the ovulation time of recipients [J]. J. Exp. Zool.,1950(114):197-226.
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