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

458 DEVELOPMENTAL REPRODUCTIVE TOXICOLOGY: A PRACTICAL APPROACH, SECOND EDITIONFlagellar development is a continuous process, continuing until sperm release. Sperm areessentially immotile when released into the lumina of the seminiferous tubules. Sperm motility isdeveloped in the epididymis, but vigorous motility occurs only after deposition into the femalereproductive tract.2. The Staging of SpermatogenesisWhile no guideline studies require staging of spermatogenesis, the FDA Redbook 2000 states“testicular tissue should be examined with a knowledge of testis structure, the process of spermatogenesis,and the classification of spermatogenesis.” This statement implies that at least the pathologistshould be aware of spermatogenesis staging. Other regulatory reproductive study guidelineshave similar statements.The classification of spermatogenesis is based on the examination of cross-sectioned seminiferoustubules, and the organization of their cells has been extensively studied in the rat. 113,114 Astage is “a defined grouping of germ cell types at particular phases of development” in crosssectionedtubules. Each cell type of the cell association is morphologically integrated with othersin its developmental processes, 115 and each stage has a defined germ cell composition. The ratspermatogenic cycle has been divided into 14 stages (Roman numerals I to XIV).Single cell associations develop and remain in one region of the tubule, called a segment.Spermatids will develop from Stage I through Stage XIV. Although the cells do not move withinthe tubule, the cell associations are distinctly arranged along the length of a tubule. Starting at therete testis and proceeding into both ends of the seminiferous tubule, segments will show a linkedorder of stages decreasing as they go further into the tubule. For example, if the initial segmentnext to the rete testis were a Stage IX, the next segment further away from the rete testis wouldbe at Stage VIII, then Stage VII, VI, and so forth. The linking of the adjacent consecutive cellassociations is called the continuity of segmental order. The pattern of decreasing segmental orderin a direction away from the rete testis is called the descent in segmental order. The descent insegmental order continues from both ends of the seminiferous tubule (away from the rete testis)until the two patterns of descent meet at a point within the tubule. This point is called the site ofreversal. The site of reversal is not equidistant from the rete testis. This decreasing segmentalpattern is not perfect, as some variations, called modulations, do occur (e.g., Stage X, IX, VIII, IX,VIII, VII). A complete series of stages along a tubule (including modulations) is called a wave ofthe seminiferous epithelium. Many waves (usually about 24) are usually present in a seminiferoustubule. In rats, a wave averages 2.6 cm in length, but waves are not uniform in length (rangingfrom 1 to 5 cm). Spermatogenesis (from spermatogonia to spermatozoa) requires about 63 d in theSprague-Dawley rat. The cell cycle duration is the time that it takes to go from Stage I to StageXIV. The cell cycle duration is 12.9 to 13.3 d in the Sprague-Dawley rat. 116A. BiologyIV. FEMALE REPRODUCTIVE TOXICOLOGYEvaluation of the rodent female reproductive system usually consists of a gross evaluation (includingorgan weights) plus a histological evaluation of the ovary, uterus, cervix, vagina, and mammary glands.Vaginal cytology is assessed for determination of the estrous cycle. Female reproductive function isregulated through complicated interactions involving the central nervous system (particularly the hypothalamus),pituitary, ovaries, the reproductive tract, and the secondary sexual organs. In addition,nongonadotrophic components of the endocrine system may also affect the female reproductive system.To understand the significance of effects on female reproductive endpoints, the relationships betweenthe reproductive hormones and the reproductive organs must be understood.© 2006 by Taylor & Francis Group, LLC