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NLRP3 在啮齿动物和灵长类动物睾丸的体细胞非免疫细胞中的表达。

NLRP3 in somatic non-immune cells of rodent and primate testes.

机构信息

Cell Biology - Anatomy IIIBiomedical Center Munich (BMC), Ludwig-Maximilians-Universität München, Martinsried, Germany.

Andrology CenterMunich, Germany.

出版信息

Reproduction. 2018 Sep;156(3):231-238. doi: 10.1530/REP-18-0111. Epub 2018 Jun 15.

Abstract

NLRP3 is part of the NLRP3 inflammasome and a global sensor of cellular damage. It was recently discovered in rodent Sertoli cells. We investigated NLRP3 in mouse, human and non-human primate (marmoset and rhesus macaque) testes, employing immunohistochemistry. Sertoli cells of all species expressed NLRP3, and the expression preceded puberty. In addition, peritubular cells of the adult human testes expressed NLRP3. and associated genes (, , ) were also found in isolated human testicular peritubular cells and the mouse Sertoli cell line TM4. Male infertility due to impairments of spermatogenesis may be related to sterile inflammatory events. We observed that the expression of NLRP3 was altered in the testes of patients suffering from mixed atrophy syndrome, in which tubules with impairments of spermatogenesis showed prominent NLRP3 staining. In order to explore a possible role of NLRP3 in male infertility, associated with sterile testicular inflammation, we studied a mouse model of male infertility. These human aromatase-expressing transgenic mice () develop testicular inflammation and impaired spermatogenesis during aging, and the present data show that this is associated with strikingly elevated expression in the testes compared to WT controls. Interference by aromatase inhibitor treatment significantly reduced increased levels. Thus, throughout species NLRP3 is expressed by somatic cells of the testis, which are involved in testicular immune surveillance. We conclude that NLRP3 may be a novel player in testicular immune regulation.

摘要

NLRP3 是 NLRP3 炎性小体的一部分,也是细胞损伤的全球传感器。它最近在啮齿动物支持细胞中被发现。我们使用免疫组织化学方法研究了小鼠、人类和非人类灵长类动物(狨猴和恒河猴)睾丸中的 NLRP3。所有物种的支持细胞都表达 NLRP3,并且这种表达发生在青春期之前。此外,成人睾丸的小管周细胞也表达 NLRP3。在分离的人睾丸小管周细胞和小鼠支持细胞系 TM4 中还发现了相关基因(、、)。由于精子发生受损导致的男性不育可能与无菌性炎症事件有关。我们观察到,患有混合萎缩综合征的患者的睾丸中 NLRP3 的表达发生了改变,在这些患者的睾丸中,具有精子发生受损的小管显示出明显的 NLRP3 染色。为了探讨 NLRP3 与无菌性睾丸炎症相关的男性不育的可能作用,我们研究了一种男性不育的小鼠模型。这些表达人类芳香酶的转基因小鼠 () 在衰老过程中会发生睾丸炎症和精子发生受损,目前的数据表明,与 WT 对照相比,睾丸中 的表达显著升高。芳香酶抑制剂治疗的干扰显著降低了升高的 水平。因此,在整个物种中,NLRP3 由睾丸的体细胞表达,这些体细胞参与睾丸免疫监视。我们得出结论,NLRP3 可能是睾丸免疫调节中的一个新的参与者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3086/6098733/ee40e2515ba8/nihms-975998-f0001.jpg

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