Testicular mast cell heterogeneity in idiopathic male infertility

Nagai, Tatsuo; Takaba, Hidenori; Miyake, Koji; Hirabayashi, Yu; Yamada, Kazuyorí

doi:10.1016/s0015-0282(16)55096-1

Cited by 35 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It therefore remains to be shown whether the tryptase-signaling pathway is of importance in all or only some cases of fibrosis. We have started to address this question by evaluating human tissues in which both fibrotic tissue remodeling and increased numbers of activated mast cells have been well documented, namely testes from infertile men (18,(29)(30)(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

“…To examine whether this newly identified pathway may be of relevance to a human fibrotic disorder, we studied human testicular biopsies from men presenting normal, mildly, or severely impaired spermatogenesis (18). We studied this tissue, because it is well documented (18,(29)(30)(31)(32)(33)) that interstitial and peritubular tryptase-positive mast cells are 2-3 times increased and show signs of activation͞ degranulation in these cases (Fig. 3a).…”

Section: Identification Of the Components Required For The Tryptase͞cmentioning

confidence: 99%

See 1 more Smart Citation

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Frungieri

Weidinger

Meineke

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

238

229

View full text Add to dashboard Cite

Mast-cell products can stimulate fibroblast proliferation, implying that these cells are key players in fibrosis. One mast-cell product, the serine protease tryptase, is known to activate protease-activated receptor 2 (PAR2) and cause proliferation of fibroblasts. We found that recombinant tryptase, human mastcell (HMC-1) supernatant, which contains tryptase, and the PAR2-activating peptide SLIGKV exert fibroproliferative actions in human fibroblasts. Here we report insights into this action, which after activation of PAR2 leads to increased expression of cyclooxygenase 2 (COX2), a key enzyme in the biosynthesis of prostaglandins, and consequently to enhanced prostaglandin synthesis. Subsequent cell proliferation is mediated by the prostaglandin 15-deoxy-⌬ 12,14 -prostaglandin J2, which acts via the nuclear peroxisome proliferator-activated receptor ␥ (PPAR␥). Fibroblast proliferation induced by tryptase and PAR2 agonist peptide can be blocked by antagonists of COX2 and PPAR␥, implying that the proliferative effect of tryptase is PAR2-initiated but depends on COX2, 15-deoxy-⌬ 12,14 -prostaglandin J2, and PPAR␥. This previously uncharacterized pathway could be of relevance for human fibrotic diseases. For instance, increased numbers of activated mast cells are correlated with fibrosis in testes of infertile men. In these cases all components of the signaling pathway of tryptase were detected as well as expression of COX2. Therefore, our study describes as-yet-unknown interactions between mast cells and fibroblasts, which could be relevant for human fibrotic diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Identification Of the Components Required For The Tryptase͞cmentioning

confidence: 99%

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Frungieri

Weidinger

Meineke

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

238

229

View full text Add to dashboard Cite

show abstract

“…Immunoreactive structures and seminiferous tubules in the same viewing area were counted and results expressed per seminiferous tubule, as described previously [37]. The evaluation of larger sections or whole testes was not possible, but since the number (in contrast to the diameter) of tubules in the testes presumably is the same in young versus adult testes, this approach provided an appropriate semiquantitative way of evaluating neuronal elements.…”

Section: Discussionmentioning

confidence: 99%

“…In each testicular section, 4–5 fields were evaluated for the presence of immunoreactive neuronal elements or mast cells and for the seminiferous tubules sectioned. The results were expressed as immunoreactive nerve fibers/tubule, immunoreactive neuron-like cells/tubule and immunoreactive mast cells/tubule as described previously [see 37]. Results obtained were statistically analyzed using ANOVA and Fisher PLSD test.…”

Section: Methodsmentioning

confidence: 99%

Neuronal Elements in the Testis of the Rhesus Monkey: Ontogeny, Characterization and Relationship to Testicular Cells

et al. 2000

View full text Add to dashboard Cite

Intrinsic neuron-like cells expressing the catecholamine-biosynthetic enzyme tyrosine hydroxylase (TH) were recently identified in the testis of the prepubertal rhesus monkey. In this study, we characterized the neuron-like nature of these cells and examined distribution and frequency of neuronal elements in the testes of monkeys during postnatal development, puberty and adulthood. Using immunohistochemical methods, we detected both nerve fibers and cell bodies, immunoreactive for the neuronal markers neurofilament 200 (NF-200) and synaptosomal associated protein of 25 kDa (SNAP-25), TH and neuropeptide Y (NPY) in perivascular locations, intermingled with interstitial cells and close to the wall of seminiferous tubules. Marked age-related differences in the numbers of these neuronal elements became apparent, when we quantified NF-200-immunoreactive neuronal elements. Thus, intrinsic neuron-like cell bodies were found only in the testes from immature animals (i.e., until about 3 years of age). Conversely, nerve fibers, presumably representing mainly the extrinsic innervation, were observed at all ages although they became more prominent after the pubertal increase in LH and testosterone levels. Interestingly, another testicular cell type known to contain potent regulatory substances, mast cells, was found to be in close anatomical proximity to nerve fibers. The number of these cells, positively identified with an antibody to tryptase, increased significantly after puberty following the same pattern as nerve fibers. These results confirm that the testicular nervous system of the monkey is composed of two components, intrinsic nerve cells and extrinsic fibers, both of which are catecholaminergic and peptidergic in nature. Furthermore, both components show a marked degree of plasticity during development, especially around the time of puberty. The intratesticular locations of neuron-like cells and fibers suggest that catecholamines and neuropeptides are likely to have multiple sites of actions, and may affect Leydig cells, cells of the tubular wall and vascular cells directly and/or indirectly via intermediation of mast cells.

show abstract

“…macrophages and mast cells ( Fig. 1; Hashimoto et al 1988, Nagai et al 1992, Apa et al 2002, Hussein et al 2005, Roaiah et al 2007. Thus, mast cell-specific genes are strikingly and robustly increased in testes samples from infertile men (Spiess et al 2007).…”

mentioning

confidence: 84%

Human testicular peritubular cells: more than meets the eye

2013

View full text Add to dashboard Cite

In healthy men, several layers of inconspicuously flat cells and extracellular matrix (ECM) proteins build the wall of the seminiferous tubules. The cells of this wall, peritubular cells, are not well characterized. They are smooth-muscle-like and contractile and transport immotile sperm, a function important for male fertility. However, their full functional importance, especially their potential contribution to the paracrine regulation of the male gonad, is unknown. In men with impaired spermatogenesis, the architecture of the tubular wall is frequently altered. Deposits of ECM and morphological changes of peritubular cells imply that functions of peritubular cells may be fundamentally altered. To be able to study human peritubular cells and their functions, a culture method was established. It is based on small biopsies of patients with obstructive azoospermia but normal spermatogenesis (human testicular peritubular cells, HTPCs) and non-obstructive azoospermia, impaired spermatogenesis, and testicular fibrosis (HTPCFs). Results obtained from cellular studies and parallel examinations of biopsies provide insights into the repertoire of the secretion products, contractile properties, and plasticity of human peritubular cells. They produce ECM components, including the proteoglycan decorin, which may influence paracrine signaling between testicular cells. They may contribute to the spermatogonial stem cell niche via secreted factors. They are regulated by mast cell and macrophage products, and in response produce factors that can fuel inflammatory changes. They possess a high degree of plasticity, which results in hypertrophy and loss of contractile abilities. The data collectively indicate important roles of inconspicuous testicular peritubular cells in human male fertility and infertility.Reproduction (2013) 145 R107-R116

show abstract

Testicular mast cell heterogeneity in idiopathic male infertility

Cited by 35 publications

References 16 publications

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: Possible relevance to human fibrotic disorders

Neuronal Elements in the Testis of the Rhesus Monkey: Ontogeny, Characterization and Relationship to Testicular Cells

Human testicular peritubular cells: more than meets the eye

Contact Info

Product

Resources

About