RNA测序结合两种不同的去势方法揭示了雄性Sprague Dawley大鼠雄激素缺乏导致颌下腺退化的新见解。

RNA-seq coupling two different methods of castration reveals new insights into androgen deficiency-caused degeneration of submaxillary gland in male Sprague Dawley rats.

作者信息

Han Xingfa, Xia Xue, Zhuo Yong, Hua Lun, Yu Guozhi, Bu Guixian, Cao Xiaohan, Du XiaoGang, Liang Qiuxia, Zeng Xianyin, Meng Fengyan

机构信息

Isotope Research Lab, Biological Engineering and Application Biology Department, Sichuan Agricultural University, Ya'an 625014, China.

Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, 611130, China.

出版信息

BMC Genomics. 2022 Apr 7;23(1):279. doi: 10.1186/s12864-022-08521-9.

DOI:10.1186/s12864-022-08521-9

PMID:35392803

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8991617/

Abstract

BACKGROUND

Salivary gland (SMG) degeneration and dysfunction are common symptoms that occur after sex hormone deprivation, but the underlying mechanisms remain largely unknown. Additionally, immunocastration, which causes drop of sex hormones, has been developed as an alternative to surgical castration, however whether it exerts similar effects as surgical castration on the salivary glands is unknown. Through histological and RNA-seq analysis, we assessed changes in morphology and transcriptome of SMG in response to immunocastration (IM) versus surgical castration (bilateral orchiectomy, ORC).

RESULTS

Compared to entire males (EM), ORC caused severe degeneration of SMG in rats, as evidenced by both decreased (P < 0.01) SMG weight and organ index, and by decreased (P < 0.01) quantity of SMG acini and ducts. IM had minimal effects (P > 0.05) on SMG weight and organ index, but it still caused degeneration (P < 0.05) of the acini and ducts. Even though, the quantity of both SMG acini and ducts was much higher (P < 0.001) in IM than in ORC. Functional enrichment analysis of the common regulated genes by ORC/IM revealed disrupted epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhanced cell death are associated with SMG degeneration in deprivation of androgens. Integrated data analysis shown that there existed a selective hyperfunction of SMG ribosome and mitochondrion in ORC but not in IM, which might be associated with more severe degeneration of SMG in ORC than in IM.

CONCLUSIONS

Our findings suggested that both surgical castration and immunocastration caused SMG degeneration by disrupting epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhancing cell death. But, surgical castration selectively induced hyperfunction of SMG ribosome and mitochondrion, thus causing more severe degeneration of SMG than immunocastration.

摘要

背景

唾液腺（SMG）退化和功能障碍是性激素剥夺后常见的症状，但其潜在机制仍 largely 未知。此外，免疫去势作为一种替代手术去势的方法已被开发出来，它会导致性激素水平下降，然而其对唾液腺的影响是否与手术去势相似尚不清楚。通过组织学和 RNA 测序分析，我们评估了免疫去势（IM）与手术去势（双侧睾丸切除术，ORC）对 SMG 形态和转录组的影响。

结果

与完整雄性大鼠（EM）相比，ORC 导致大鼠 SMG 严重退化，SMG 重量和器官指数降低（P < 0.01）以及 SMG 腺泡和导管数量减少（P < 0.01）均证明了这一点。IM 对 SMG 重量和器官指数影响极小（P > （此处原文有误，推测为P > 0.05）），但仍导致腺泡和导管退化（P < 0.05）。即便如此，IM 组中 SMG 腺泡和导管的数量均比 ORC 组高得多（P < 0.001）。对 ORC/IM 共同调控基因的功能富集分析表明，上皮细胞发育、血管生成、解剖结构形态发生的破坏以及细胞死亡增加与雄激素剥夺时 SMG 退化有关。综合数据分析显示，ORC 组中存在 SMG 核糖体和线粒体的选择性功能亢进，而 IM 组中不存在，这可能与 ORC 组中 SMG 比 IM 组更严重的退化有关。