From testis to teratomas: a brief history of male germ cells in mammals MASSIMO DE FELICI* and SUSANNA DOLCI Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy ABSTRACT In antiquity, many theories were advanced on reproduction and the functions of the gonads. The male genitalia were called “testes” probably from the Latin word “testis “ that origi- nally meant “witnesses” , because they provide evidence of virility. Through the first dissection of the seminipherous tubules by Renier de Graaf (1668), the discovery of spermatozoa by Antonj van Leeuwenhoek (1677) and in vitro fertilization by Spallanzani (1780) and later by George Newport and George Vines Ellis (1854), it was only in the early part of the XIX century when it was realized that testes produce spermatozoa and that they are essential for egg fertilization and subsequent embryo development. In the period between the end of the XIX and the beginning of the XX cen- tury, scientists such as Albert von Kölliker (1817-1910), Franz von Leydig (1821-1908), Enrico Sertoli (1842-1910) and Gustaf Retzius (1842-1919) did microscopic observations of testis that marked the history of male germ cells and established the bases for the development of contemporary in vitro culture and molecular studies that are revealing the deeper secrets of male germ cells. Among these, those by Leroy Stevens on embryonal carcinoma cells in the early 1950s led to the present concepts that germ cells and cancer cells share several characteristics and that a close relationship exists between germ cells and stem cells, these being two pillars of modern developmental biology. KEY WORDS: germ cell, teratoma, teratocarcinoma, testis, stem cell From Aristotle to the Reinaissance Although it was appreciated from the antiquity that removal of gonads had evident consequences for the fertility and behaviour of men, the anatomy and function of the gonads were essentially unknown in the ancient times. In antiquity, many theories were advanced on reproduction and the signifcance of the gonads. Until the Renaissance, most physicians described the male and female reproductive organs as counterparts of each other and wrote of homologous anatomical structures. Words such as “tes- tes” were applied to both male and female reproductive organs, since it was believed that both produce substances by similar processes that contributed to generation. What that substance was became a matter of heated debate. The male genitalia were called “testes” probably from the Latin word “testis “ that originally meant “witnesses”, because they provide evidence of virility. In the fourth century B.C., Aristotle wrote that man contributed the form of humanity through his semen, while woman contributed only brute matter, a substance less pure and less sanctifed than semen itself. Hippocrates and Galen preferred to describe human Int. J. Dev. Biol. 57: 115-121 (2013) doi: 10.1387/ijdb.130069md www.intjdevbiol.com *Address correspondence to: Massimo De Felici. Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Roma, Italy. e-mail: defelici@uniroma2.it Final, author-corrected PDF published online: 5 June 2013. ISSN: Online 1696-3547, Print 0214-6282 © 2013 UBC Press Printed in Spain Abbreviations used in this paper: EC cell, embryonic carcinoma cell; PGC, primordial germ cell. conception as occurring from two “seeds” though they differed slightly on the relative importance of the male and female contri- bution. Debates about the different seeds continued throughout the Middle Ages. According to the Galenic model, both men and women were believed to have “seminal vessels” that carried se- men to its point of exit. How male semen was generated was a source of speculation. Galen argued that semen came from the testes but other sources were hypothesized. Did it come from the brain via the spinal cord? Was it produced from blood? From the Renaissance onward, the development of human anatomy begun to change the traditional images of the reproductive organs and the vocabulary for the male and female bodies slowly became much more specifc to each sex. At the end of the XV century, Leonardo’s in his earliest anatomical drawings (about 1493) depicting sexual intercourse, admirably summarizes the traditional views of that time about the origin of semen (Fig. 1). Notably, in the middle of XVI, Andreas Vesalius (1514-1564), considered the father of the