PDF(Pubmed)
Abstract：
The current study aimed to investigate the effect of Sox9-Cre-directed Nr5a1-conditional knockout (Sox9-Cre;Nr5a1flox/flox) on adrenal development. We showed that SOX9 is expressed by adrenocortical cells at E10.5-E11.5 but is extinguished no later than E12.5. The number of adrenocortical cells significantly reduced in Sox9-Cre;Nr5a1flox/flox mice while the number of cleaved caspase 3-positive cells increased compared to that in the controls at E11.5-E12.5, when the adrenal primordium (AP) is about to expand. This indicated that fetal adrenocortical cells are lost via apoptosis due to Nr5a1 ablation by E12.5. Both medulla formation and encapsulation were perturbed, accompanied by a smaller AP size, in Sox9-Cre;Nr5a1flox/flox mice during embryonic development. Adult Sox9-Cre;Nr5a1flox/flox adrenals were hypoplastic and exhibited irregular organization of the medulla with aberrant sex differentiation in the X zone. Additionally, there were histologically eosin-negative vacuolated cells, which were negative for both the X-zone marker 20αHSD and the steroidogenesis marker 3βHSD at the innermost cortex of Sox9-Cre;Nr5a1flox/flox adrenals. Although Nr5a1+/- adrenals were hypoplastic, a small number of chromaffin cells were properly located in the center, having normal sex differences in the X-zone. The results collectively provided in-vivo evidence that Nr5a1 plays a critical role in AP expansion and subsequent adrenal development.
摘要：
本研究旨在研究Sox9-Cre定向的Nr5a1条件敲除（Sox9-Cre;Nr5a1flox/flox）对肾上腺发育的影响。我们发现SOX9在E10.5-E11.5由肾上腺皮质细胞表达，但不迟于E12.5。Sox9-Cre;Nr5a1flox/flox小鼠的肾上腺皮质细胞数量显着减少，而当肾上腺原基（AP）即将扩张时，与E11.5-E12.5的对照相比，裂解的caspase3阳性细胞数量增加。这表明由于E12.5的Nr5a1消融，胎儿肾上腺皮质细胞通过凋亡而丢失。髓质形成和包封都受到干扰，伴随着较小的AP尺寸，在Sox9-Cre；Nr5a1flox/flox小鼠胚胎发育过程中。成人Sox9-Cre；Nr5a1flox/flox肾上腺发育不良，髓质组织不规则，X区性别分化异常。此外,组织学上有伊红阴性的空泡细胞，Sox9-Cre最内层皮质的X区标记20αHSD和类固醇生成标记3βHSD均为阴性；Nr5a1flox/flox肾上腺。尽管Nr5a1+/-肾上腺发育不良，少量的嗜铬细胞位于中心，在X区具有正常的性别差异。结果共同提供了体内证据，表明Nr5a1在AP扩张和随后的肾上腺发育中起关键作用。
