Rehm Sabine, White Tacey E, Zahalka Eias A, Stanislaus Dinesh J, Boyce Rogely W, Wier Patrick J
GlaxoSmithKline, King of Prussia, Pennsylvania 19301, USA.
Toxicol Pathol. 2008 Jul;36(5):687-94. doi: 10.1177/0192623308320275. Epub 2008 Jul 22.
Reduced food consumption and associated lower body weights may occur in subacute toxicity studies. The short-term effects of food restriction (FR) on body and reproductive organ weights, hormones, and testis histology were assessed in Sprague-Dawley rats fed 20% to 36% less (21 g feed/day) than rats fed ad libitum (AL) starting at six, eight, ten, or twelve weeks of age for two or six weeks. Body weight and relative seminal vesicle, ventral prostate, and/or epididymis weights were reduced in rats FR for two or six weeks. Degeneration of stage VII pachytene spermatocytes was seen in rats FR for six weeks when initiated at eight, ten, and twelve weeks of age. Plasma testosterone concentrations were lower in rats FR at ages six to eight weeks, eight to ten weeks, six to twelve weeks, and eight to fourteen weeks. Luteinizing hormone was not statistically different in FR rats compared with AL counterparts. Therefore, duration of lower food intake had a greater impact on spermatogenesis, whereas a younger initial age of lower food intake was more influential on testosterone levels. These interactions are important in the interpretation of subacute toxicology studies employing FR or when test articles lower food consumption relative to AL-fed rats.
在亚急性毒性研究中可能会出现食物摄入量减少以及随之而来的体重降低。在6周、8周、10周或12周龄开始的为期2周或6周的实验中，对斯普拉格-道利大鼠进行食物限制（FR），使其食物摄入量比自由采食（AL）的大鼠减少20%至36%（每天21克饲料），评估食物限制对体重、生殖器官重量、激素和睾丸组织学的短期影响。进行2周或6周食物限制的大鼠体重以及精囊、腹侧前列腺和/或附睾的相对重量降低。在8周、10周和12周龄开始进行6周食物限制的大鼠中，观察到VII期粗线期精母细胞发生退化。在6至8周龄、8至10周龄、6至12周龄和8至14周龄进行食物限制的大鼠中，血浆睾酮浓度较低。与自由采食的大鼠相比，食物限制大鼠的促黄体生成素没有统计学差异。因此，较低食物摄入量的持续时间对精子发生的影响更大，而较低食物摄入量开始时的年龄越小，对睾酮水平的影响越大。在解释采用食物限制的亚急性毒理学研究或当受试物相对于自由采食的大鼠降低食物摄入量时，这些相互作用很重要。
