Department of Surgery, Capital Institute of Pediatrics affiliated Children Hospital, Beijing100020, China.
Department of Anatomy, Wuxi School of Medicine, Jiangnan University, WuXi, Jiangsu214122, China.
J Dev Orig Health Dis. 2022 Feb;13(1):61-67. doi: 10.1017/S2040174421000088. Epub 2021 Apr 12.
Intestinal atresia (IA), a common cause of neonatal intestinal obstruction, is a developmental defect, which disrupts the luminal continuity of the intestine. Here, we investigated (i) the process of lumen formation in human embryos; and (ii) how a defective lumen formation led to IA. We performed histological and histochemical study on 6-10 gestation week human embryos and on IA septal regions. To investigate the topology of embryonic intestine development, we conducted 3D reconstruction. We showed that a 6-7th gestation week embryonic gut has no lumen, but filled with mesenchyme cells and vacuoles of a monolayer of epithelial cells. A narrow gut lumen was formed by gestation week-9, the gut was filled with numerous vacuoles of different sizes, some vacuoles were merging with the developing embryonic gut wall. At gestation week-10, a prominent lumen was developed, only few vacuoles were present and were merging with the intestine wall. At IA septal regions, vacuoles were located in the submucous layer, covered by a single layer of epithelium without glandular structure, and surrounded with fibrous tissue. The mucosal epithelium was developed with lamina propria and basement membrane, but the submucosa and the longitudinal smooth muscle layers were not properly developed. Hence, the vacuoles in IA septum could represent a remnant of vacuoles of embryonic gut. In conclusion, the fusion of vacuoles with the developing intestine wall associates with the disappearance of vacuoles and gut lumen formation in human embryos, and perturbation of these developmental events could lead to IA.
肠闭锁（IA）是新生儿肠梗阻的常见原因，是一种发育缺陷，会破坏肠腔的连续性。在这里，我们研究了（i）人胚肠道内腔形成的过程；以及（ii）缺陷的内腔形成如何导致 IA。我们对 6-10 孕周的人胚和 IA 隔膜区进行了组织学和组织化学研究。为了研究胚胎肠发育的拓扑结构，我们进行了 3D 重建。我们表明，6-7 孕周的胚胎肠道没有内腔，而是充满了间充质细胞和单层上皮细胞的空泡。在 9 孕周时形成了狭窄的肠道内腔，肠道充满了许多大小不一的空泡，一些空泡与正在发育的胚胎肠壁融合。在 10 孕周时，形成了明显的内腔，只有少数空泡存在，并与肠壁融合。在 IA 隔膜区，空泡位于黏膜下层，被单层无腺体结构的上皮细胞覆盖，周围是纤维组织。黏膜上皮具有固有层和基底膜，但黏膜下层和纵行平滑肌层发育不良。因此，IA 隔膜中的空泡可能代表胚胎肠道空泡的残余物。总之，空泡与正在发育的肠壁融合与空泡和人胚肠道内腔形成的消失有关，这些发育事件的干扰可能导致 IA。
