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NLRP3 in somatic non-immune cells of rodent and primate testes
ISSN
1470-1626
Date Issued
2018
Author(s)
Walenta, Lena
Schmid, Nina
Schwarzer, J Ullrich
Köhn, Frank-Michael
Urbanski, Henryk F
Strauss, Leena
Poutanen, Matti
Mayerhofer, Artur
DOI
10.1530/REP-18-0111
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.
NLRP3
and associated genes (
PYCARD
,
CASP1
,
IL1B
) 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 (
AROM+
) develop testicular inflammation and impaired spermatogenesis during aging, and the present data show that this is associated with strikingly elevated
Nlrp3
expression in the testes compared to WT controls. Interference by aromatase inhibitor treatment significantly reduced increased
Nlrp3
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.
NLRP3
and associated genes (
PYCARD
,
CASP1
,
IL1B
) 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 (
AROM+
) develop testicular inflammation and impaired spermatogenesis during aging, and the present data show that this is associated with strikingly elevated
Nlrp3
expression in the testes compared to WT controls. Interference by aromatase inhibitor treatment significantly reduced increased
Nlrp3
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.