Integrin Pattern and Effect on Contraction in Cultured Testicular Peritubular Myoid Cells

Magnanti, Massimo; Gismondi, Angela; Gandini, Orietta; Morrone, Stefania; Rossi, Fábio; Santiemma, V.; Michetti, Paolo

doi:10.1111/j.8755-8920.2001.450104.x

Cited by 6 publications

(4 citation statements)

References 29 publications

(35 reference statements)

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“…ICAM-1 is regulated by several factors including lipopolysaccharide or TNF-␣ in multiple cell types (54). Interestingly, ICAM-1 was found in one of the very few studies addressing human peritubular cells (16). The authors of this study used enzymatic digestion to prepare their cultures and found strong expression of ICAM-1, whereas in our cell system of explant cultures, it was not found.…”

Section: Discussionmentioning

confidence: 63%

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Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

et al. 2008

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Testicular peritubular cells are myofibroblastic cells, which represent the major cellular components of the wall of the seminiferous tubules. In men their phenotypic characteristics, including possible secretory activity and regulation, are not well known, in neither normal nor pathologically altered testes. Especially in testes of men with impaired spermatogenesis, the cytoarchitecture of the tubular wall is frequently remodeled and presents fibrotic thickening, increased innervation, and infiltration by macrophages and mast cells. The latter are two sources of TNF-alpha. The purpose of our study was to explore human testicular peritubular cells and mechanisms of their regulation. To this end we primarily studied cultured human testicular peritubular cells (HTPCs), isolated from adult human testes. Having established that HTPCs express TNF-alpha receptors 1 and 2 and respond to recombinant human TNF-alpha by a rapid phosphorylation of ERK1/2, we used complementary approaches, including gene array/RT-PCR studies, Western blotting/immunocytochemistry, and ELISA techniques to study phenotypic characteristics of HTPCs and actions of TNFalpha. We found that HTPCs express the nerve growth factor gene and TNF-alpha-stimulated mRNA levels and secretion of nerve growth factor in a dose- and time-dependent manner. Similarly, monocyte chemoattractant protein-1 was identified as a product of HTPCs, which was regulated by TNF-alpha in a concentration- and time-dependent manner. TNF-alpha furthermore strongly enhanced expression and/or synthesis of other inflammatory molecules, namely IL-6 and cyclooxygenase-2. Active cyclooxygenase-2 is indicated by increased prostaglandin D2 levels. In addition, intercellular adhesion molecule-1, which was not detected at protein level in the absence of TNF-alpha, was induced upon TNF-alpha stimulation. In conclusion, these results provide novel insights into the nature of human peritubular cells, which are able to secrete potent signaling molecules and are regulated by TNF-alpha. These results also hint to an as-yet-unknown role of peritubular cells in normal human testis and involvement in the pathomechanisms associated with impaired spermatogenesis in men.

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Section: Discussionmentioning

confidence: 63%

“…Previously only very few studies have dealt with human peritubular cell cultures (15,16). Enzymatic dispersion techniques or infantile tissues as source of peritubular cells have been described.…”

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confidence: 99%

Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

et al. 2008

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“…SC and PMC are responsible for the maintenance of the tubular histoarchitecture and the blood-testis barrier [42]. These cells produce specific components of the peritubular tissue extracellular matrix [43][44][45], express several types of alfa and beta integrin subunits [46] and synthesize factors that regulate SC functions [47]. The adherence of SC to the basement membrane has been mediated by integrin α6β1 [48].…”

Section: Effect Of Busulphan On the Peritubular Myoid And Leydig Cellsmentioning

confidence: 99%

The antineoplastic busulphan impairs peritubular and Leydig cells, and vitamin B12 stimulates spermatogonia proliferation and prevents busulphan-induced germ cell death

Sasso-Cerri

Oliveira

Santi

et al. 2017

Biomedicine & Pharmacotherapy

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Busulphan (Bu), an alkylating agent used for bone marrow and spermatogonial stem cell transplantation (SSCT), impairs Sertoli (SC) cells, which are necessary for the spermatogonial stem cell (SSC) homing during transplantation. As Leydig (LC) and peritubular myoid (PMC) cells are essential for SC support and maintenance of spermatogonial niche, we evaluated the impact of Bu on the LC and PMC structural integrity. Vitamin B (B) has demonstrated beneficial effects against drug-induced testicular changes; thus, we also examined whether this vitamin is able to stimulate spermatogonia mitotic activity and prevent Bu-induced germ cell death. Rats received 10mg/kg of Bu in the 1st and 4th days, and daily B supplementation during Bu treatment and for 6days after the last injection of Bu (Bu-6d), totaling 10days of treatment. Other animals received the same treatment as Bu-6d, and B supplementation (Bu+7dB) or saline (Bu+7dS) for 7 more days, totaling 17days of treatment. Serum testosterone levels were measured. In the historesin-embedded testis sections, the seminiferous tubule and epithelial areas were measured, and the number of spermatogonia and PMC was quantified. Actin and 17β-HSD6 immunofluorescence was detected, and the number of TUNEL-positive LC and germ cells was computed. In Bu-6d, PMC number reduced, and a weak actin immunoexpression and death in these cells was observed. The testosterone levels reduced, and the interstitial tissue showed a weak 17β-HSD6 immunoexpression and increased number of TUNEL-positive LC. In Bu+7dB, the number of spermatogonia was higher than in Bu-6d and Bu+7dS, and the number of TUNEL-positive germ cells was significantly lower than in Bu+7dS. Bu exerts a harmful impact on PMC and LC, reducing the testosterone levels. Vitamin B prevents significantly Bu-induced germ cell death and stimulates spermatogonia proliferation, being a useful strategy for the enrichment of SSC in vitro and an adjuvant therapy for spermatogenesis recovery in oncologic patients.

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“…Gonadotrophins and their associated signaling factors such as KISS1, FSH, LH, and INHBA are hormonal regulators of the reproductive axis, [ 41 ] while integrins such as ICAM1 are responsible for PTM contractility. [ 42 ] PDGF signaling is an important regulator of PTM and Leydig cell fate acquisition, while prostanoids such as prostaglandin F2a are modulators of PTM contractility. [ 43 ] WNT1, a pathway associated with pluripotency and primitive streak progenitor regulation, [ 44 ] was enriched in the DL01 hiPSC‐PTMs in comparison to the 11‐10 hiPSC‐PTMs in keeping with a less differentiated state.…”

Section: Discussionmentioning

confidence: 99%

Differentiation of Peritubular Myoid‐Like Cells from Human Induced Pluripotent Stem Cells

Robinson¹,

Haegert²,

Li³

et al. 2023

Advanced Biology

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treatments is hampered due to our limited understanding of the underlying function of normal human testicular cell-typespecific function, as well as cell-type-specific dysfunction contributing to spermatogenic failure. The somatic cells contributing to the spermatogenic niche include Sertoli cells, peritubular myoid cells (PTMs), Leydig cells, macrophages, and endothelial cells. PTMs, in combination with Sertoli cells, constitute a barrier surrounding the seminiferous tubules. A frequent finding in the cellular histology of infertile males is defects in the architecture of this barrier, suggesting a dysregulation in its formation or regulation, [2] and consequently the local spermatogenic microenvironment. [3] PTMs occupy the boundary separating the interstitial Leydig cell compartment from the germ cell tubular compartment, and contribute an important element to seminiferous tubule cytoarchitecture and cell regulation within the somatic niche (Figure 1). PTMs remain poorly characterized despite their importance. Our understanding of PTMs is derived predominately from rodent cell cultures and knock-out mouse models. These in vitro and in vivo studies have shown that PTMs are responsive to androgen stimulation, as evidenced by increased secretion Infertility affects 10-15% of couples, with half attributed to male factors. An improved understanding of the cell-type-specific dysfunction contributing to male infertility is needed to improve available therapies; however, human testicular tissues are difficult to obtain for research purposes. To overcome this, researchers have begun to use human induced pluripotent stem cells (hiPSCs) to generate various testis-specific cell types in vitro. Peritubular myoid cells (PTMs) are one such testicular cell type that serves a critical role in the human testis niche but, to date, have not been derived from hiPSCs. This study set forth to generate a molecular-based differentiation method for deriving PTMs from hiPSCs, mirroring in vivo patterning factors. Whole transcriptome profiling and quantitative polymerase chain reaction (qPCR) show that this differentiation method is sufficient to derive cells with PTM-like transcriptomes, including upregulation of hallmark PTM functional genes, secreted growth and matrix factors, smooth muscle, integrins, receptors, and antioxidants. Hierarchical clustering shows that they acquire transcriptomes similar to primary isolated PTMs, and immunostaining shows the acquisition of a smooth muscle phenotype. Overall, these hiPSC-PTMs will allow in vitro study of patient-specific PTM development and function in spermatogenesis and infertility.

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Integrin Pattern and Effect on Contraction in Cultured Testicular Peritubular Myoid Cells

Abstract: Our investigation documented a broad integrin pattern on human cultured TPMC as well as a role for integrins in human and rat TPMC contraction.

Cited by 6 publications

References 29 publications

Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

The antineoplastic busulphan impairs peritubular and Leydig cells, and vitamin B12 stimulates spermatogonia proliferation and prevents busulphan-induced germ cell death

Differentiation of Peritubular Myoid‐Like Cells from Human Induced Pluripotent Stem Cells

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