Department of Pediatric Surgery, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), 6431 Fannin Street, Suite 5.258, Houston, TX, 77030, USA.
Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, 6450 E Cullen St, BCMN-N1301, Houston, TX, 77030, USA.
Dig Dis Sci. 2022 Dec;67(12):5511-5521. doi: 10.1007/s10620-022-07442-7. Epub 2022 Mar 25.
Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.
We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.
HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR performed. Morphology was evaluated and epithelial architecture graded on a scale of 1 (absence of crypts/villi) to 4 (elongated crypt-villus axis). RT-qPCR and immunofluorescence microscopy were performed for epithelial and mesenchymal differentiation markers.
Host survival and tHIO engraftment were equivalent in male and female hosts. tHIO weight and length were also equivalent between groups. The number of lumens per tHIOs from male and female hosts was similar, but the mean lumen circumference was larger for tHIOs from male hosts. tHIOs from male hosts were more likely to demonstrate higher grades of epithelial development. However, both groups showed similar differentiation into secretory and absorptive epithelial lineages. Markers for intestinal identity, mesenchymal development, and brush border enzymes were also expressed similarly between groups.
While male host sex was associated with larger tHIO lumen size and mucosal maturation, tHIOs from both groups had similar engraftment, growth, and epithelial and mesenchymal cytodifferentiation.
将人类肠类器官（HIOs）移植到免疫缺陷小鼠（tHIOs）中，可观察到其显著的生长和成熟。虽然雄性和雌性小鼠均被报道为这些实验的可行宿主，但尚未直接比较 tHIO 结构和发育方面的性别差异。
我们旨在确定宿主性别相关的 tHIO 植入、形态以及上皮和间充质发育的差异。
体外生成 HIOs，并移植到 NSG 雄性和雌性小鼠的肾包膜下。在 8-9 周时收获 tHIOs。记录人体测量学指标。将 tHIOs 分成两半，进行组织学或 RT-qPCR 检测。评估形态，并根据隐窝/绒毛轴的长度将上皮结构分级（1 级：无隐窝/绒毛；4 级：隐窝-绒毛轴拉长）。进行 RT-qPCR 和免疫荧光显微镜检测，以评估上皮和间充质分化标志物。
雄性和雌性宿主的宿主存活率和 tHIO 植入率相当。tHIO 的重量和长度在两组间也无差异。来自雄性和雌性宿主的 tHIOs 的每个管腔数量相似，但来自雄性宿主的 tHIOs 的平均管腔周长更大。来自雄性宿主的 tHIOs 更有可能表现出更高等级的上皮发育。然而，两组在分泌和吸收上皮谱系的分化方面均表现出相似的特征。肠特异性标志物、间充质发育标志物和刷状缘酶也在两组间相似表达。
尽管雄性宿主性别与更大的 tHIO 管腔大小和黏膜成熟度相关，但两组的 tHIO 均具有相似的植入、生长以及上皮和间充质细胞分化。
