Yamazaki Masaki, Fujii Etsuko, Watanabe Takeshi, Kato Atsuhiko, Suzuki Masami
Research Division, Chugai Pharmaceutical Co., Ltd., 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan.
Forerunner Pharma Research Co., Ltd., Komaba Open Laboratory, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
J Toxicol Pathol. 2020 Jan;33(1):39-46. doi: 10.1293/tox.2019-0032. Epub 2019 Sep 23.
Pathological evaluation of juvenile toxicity studies requires the understanding of normal tissue development at different ages. Here, we report the morphological features of the neonatal mouse intestine, focusing on crypt fission. Postnatal day (PND) 7 and 14 mice showed fewer crypts and less mature epithelial morphology compared to PND 21 and 28. Crypt fission occurred in three stages: 1) flattening of the crypt base into a skirt shape, 2) penetration of myofibroblasts into the crypt base center, and 3) complete separation of a single crypt into two daughter crypts. The ratio of crypt fission to total number of crypts was the highest at PND 14 and 7 in the jejunum and colon, respectively. Crypt fission, a key phenomenon for balance or imbalance in epithelial cell hierarchy, including stem and differentiated cells, is related to tissue injury repair and tumorigenesis. Therefore, examining crypt fission can provide valuable insights into current conditions of intestine.
幼年毒性研究的病理学评估需要了解不同年龄阶段的正常组织发育情况。在此，我们报告新生小鼠肠道的形态学特征，重点关注隐窝裂变。与出生后第21天和28天的小鼠相比，出生后第7天和14天的小鼠隐窝较少，上皮形态也不太成熟。隐窝裂变分为三个阶段：1）隐窝底部扁平呈裙状；2）肌成纤维细胞侵入隐窝底部中心；3）单个隐窝完全分离为两个子代隐窝。在空肠和结肠中，隐窝裂变与隐窝总数的比率分别在出生后第14天和第7天最高。隐窝裂变是上皮细胞层级（包括干细胞和分化细胞）平衡或失衡的关键现象，与组织损伤修复和肿瘤发生有关。因此，检查隐窝裂变可为了解肠道当前状况提供有价值的见解。
