Mammalian Sperm, Eggs, and Control of Fertility

MAMMALIAN SPERM, EGGS, AND CONTROL OF FERTILITY M. C. CHANG, PkD.* My Association with Gregory Pincus In the early spring of 1945 I left Cambridge University to work at the Worcester Foundation for Experimental Biology, Massachusetts, newly established by Hudson Hoagland and Gregory Pincus. When I went to Pincus' office the morning after my arrival, he gave me a carbon copy of an itemized oudine of our research project which essentially included perfusion of cow ovaries, inducing superovulation, finding the eggs, mixing them with sperm and fertilizing them in vitro, then transferring them to different cows. Analysis of chemical components of the perfusate was assigned to my co-worker. I was quite startled and asked Pincus whether we could finish this project in one year. He looked at me with his penetrating eyes and said, "Sure, at least we could try." I thought, what an imagination and what an American style of efficiency, for this seemed more like a project for my whole life, and I was only planning to stay for a year! After several months ofhard work with Drs. Clara Szego and N.Werthessen, we managed to induce ovulation in one ovary. Dr. Pincus was pleased, and everyone was excited and happy, except me perhaps , because I did not try to find the egg. At that time I received a letter from the late SirJoseph Barcroft, who asked me to convey his best regards to Dr. Pincus, and wrote, "There is much to be learned from perfused organs: but remember that in the last resort they are perfused organs." When I showed this letter to Dr. Pincus, he chuckled and said, "Isn't that rather typical ofDr. Barcroft?" Later on, I asked him ifI might be released from the perfusion project. He asked me, "What would you like to do?" I said, "To continue my study of the * Senior scientist, Worcester Foundation for Experimental Biology, Shrewsbury, Mass.; research professor, Boston University, Boston; and Research Career Awardee of the National Institute of Child Health and Human Development. 376 M. C. Chang · Control ofFertility Perspectives in Biology and Medicine · Spring 1968 fertilizing capacity ofsperm." He smiled and said, "Do you know what ProfessorGoldschmidtofGermanysaid to me after Iworked inhis laboratory for one year? He said that I am very fertilizing." Thus, the "stimulating " personality of Pincus was appreciated by a famous geneticist, although the word "fertilizing" was somewhat misused. When he looked over my outline ofstudy, he touched his moustache with his thumb and said, "Yes, I'll find some rabbits for you. You can carry on your study according to your plan in your spare time. Perfusion will not take all your time. Fertilizing Capacity ofSperm Spermatozoa, as a type of cell, have many fascinating and interesting features, but they are particularly differentiated for motility and fertilization . Motility ofsperm has been studied by many scientists from Leeuwenhoeck to Sir James Gray and Lord Rothschild [i]. A scientist trained in any discipline and with different research interests can still utilize sperm as material for his study. As an experimental biologist, I chose to study the fertilizing capacity ofsperm because it would be more direct and more reliable to ascertain the functional integrity ofspermatozoa, to reveal the mechanism of fertilization, and to understand better male fertility and sterility [2, 3]. There are, however, many problems in connection with the fertilizing capacity of sperm which are still obscure. For instance, how does their fertilizing capacity develop? We know that sperm removed from the caput of the epididymis not only are unable to fertilize the eggs but are incapable of establishing contact with the surface of the egg [4]. After their formation, they have to spend one or two weeks in the epididymis to fulfil this function. How is it that their fertilizing capacity can be preserved for thirty-eight days in the cauda ofthe epididymis but is lost within thirty hours in the female tract [5]? The basis for their resistance to pH, osmotic changes, or irradiation in vitro is another question [6, 7]. In fact, Hoagland and Pincus [8] have shown revival ofmammalian sperm after immersion in liquid nitrogen (—196° C). Bull spermatozoa can be kept at —79o C. for many months...