Picut Catherine A, Remick Amera K, de Rijk Eveline P C T, Simons Michelle L, Stump Donald G, Parker George A
WIL Research, Hillsborough, North Carolina, USA
WIL Research, Hillsborough, North Carolina, USA.
Toxicol Pathol. 2015 Apr;43(3):326-42. doi: 10.1177/0192623314547279. Epub 2014 Sep 11.
Histopathologic examination of the testis from juvenile rats is often necessary to characterize the safety of new drugs for pediatric use and is a required end point in male pubertal development and thyroid function assays. To aid in evaluation and interpretation of the immature testis, the characteristic histologic features of the developing rat testis throughout postnatal development are described and correlated with published neuroendocrine parameter changes. During the neonatal period (postnatal day [PND] 3-7), seminiferous tubules contained gonocytes and mitotically active immature Sertoli cells. Profound proliferation of spermatogonia and continued Sertoli cell proliferation occurred in the early infantile period (PND 8-14). The spermatogonia reached maximum density forming double-layered rosettes with Sertoli cells in the late infantile period (PND 15-20). Leptotene/zygotene spermatocytes appeared centrally as tubular lumina developed, and individual tubules segregated into stages. The juvenile period (PND 21-32) featured a dramatic increase in number and size of pachytene spermatocytes with the formation of round spermatids and loss of "infantile" rosette architecture. In the peri-pubertal period (PND 32-55), stage VII tubules containing step 19 spermatids were visible by PND 46. The presented baseline morphologic and endocrinologic information will help pathologists distinguish delayed development from xenobiotic effects, determine pathogenesis when confronted with nonspecific findings, and identify sensitive time points for targeted study design.
对幼年大鼠睾丸进行组织病理学检查，对于确定新药用于儿科的安全性往往是必要的，并且是雄性青春期发育和甲状腺功能测定所需的终点。为了帮助评估和解释未成熟睾丸，本文描述了出生后发育过程中大鼠睾丸发育的特征性组织学特征，并将其与已发表的神经内分泌参数变化相关联。在新生儿期（出生后第3 - 7天），生精小管含有生殖母细胞和有丝分裂活跃的未成熟支持细胞。精原细胞大量增殖以及支持细胞持续增殖发生在婴儿早期（出生后第8 - 14天）。在婴儿晚期（出生后第15 - 20天），精原细胞达到最大密度，与支持细胞形成双层玫瑰花结。随着管状腔的发育，细线期/偶线期精母细胞出现在中央，各个小管开始分化为不同阶段。幼年时期（出生后第21 - 32天）的特征是粗线期精母细胞数量和大小急剧增加，同时形成圆形精子细胞，“婴儿期”玫瑰花结结构消失。在青春期前期（出生后第32 - 55天），到出生后第46天可见含有第19步精子细胞的VII期小管。本文提供的基线形态学和内分泌学信息将有助于病理学家区分发育延迟与外源化合物的影响，在面对非特异性发现时确定发病机制，并确定靶向研究设计的敏感时间点。
