A Practical Approach, Second Edition=Ronald D. Ho.pdf

1034 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONIn male rats, the first spermatozoa appear in the lumen of the seminiferous tubules at 45 daysof age 31 and transit through the epididymis to the vas deferens, where they can be detected at 58-59 days of age. 32 Testicular sperm reach a plateau by 77 days of age. 30In contrast to these values, Maeda et al. cited the following postnatal developmental time linesfor Wistar rats: 33 testicular spermatids first appear in the testis at day 20-30 after birth and 100%of animals contain testicular sperm at day 70. In the tail of the epididymis, some males containsperm at approximately day 40 and almost all animals do so by day 90. The relative weights ofthe testis and epididymis reach their peak value at around day 70. Testicular weight is around 1%of body weight at 50 days after birth, the time of puberty.It is important to note that the first wave or two of spermatogenesis in rats is quite inefficient,and there is much greater cell loss peripubertally than there is in adult rats. 34 Thus, studies evaluatinganimals peripubertally should expect to see greater levels of cell death and structural abnormalitiesin the controls, which will complicate the identification of such effects in treated animals. Thetestes continue to increase in size after puberty due to increased total sperm production, althoughproduction per unit weight of the testis rapidly reaches a maximal value. 211.1.4 MousePrenatally, germ cells and Sertoli cells migrate from the mesonephric ridge much as in the rat. 35Postnatally, the earliest Type A spermatogonia can be observed at PND 3, and these are proliferating.Sertoli cells proliferate until PND17 under the influence of pituitary gonadotrophins. 36,37,38 Leydigcells proliferate much later, closer to puberty (PND 21-33), 15 and this is dependent on gonadotrophinin serum. 38 Puberty in the mouse is approximately PND 35.1.1.5 DogTestis differentiation was observed at GD 36 in Schnauzers and beagles; 39 this was followed closelyby regression of the Müllerian ducts. Postnatally, the seminiferous tubules are composed of immatureSertoli cells and gonocytes at 2 weeks of age. During the first 3 postnatal weeks, the Leydigcells appear to be mature, then they appear to regress from weeks 4 to 7, although there is noappreciable change in androgen levels. At 8 weeks of age, Leydig cells appear to be active andmitotic figures can be found in both Sertoli cells and spermatogonia. Between 16 and 20 weeks,the number of germ cells per cross section of cord decreases and the amount of lipid increases. At16 weeks, evidence for the leptotene stage of meiotic prophase is evident as condensed spermatogonialchromatin. 40 At wk 18-20, the germ cells begin their rapid division, and tubule cellularity anddiameter increase rapidly. 41 Round spermatids begin to appear at wk 22, long spermatids at wk 26,and by wk 28 in beagles, diameter is nearly at adult values, when all cell types are represented.1.2 Epididymides1.2.1 HumanAs with other mammals, development of the epididymis is dependent upon androgens from thetesticular Leydig cells. Furthermore, differentiation of the epididymal epithelium is dependent uponconstituents of luminal fluid from the testis or proximal epididymis. 421.2.2 RatLike the testis, the epididymis arises embryologically from the middle of three nephroic regionsin the fetus. The most caudal region gives rise to the kidney. The cells in the mesonephros, incontrast, migrate caudally, and forms a diffuse networks of ducts. In the presence of Müllerian© 2006 by Taylor & Francis Group, LLC