Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients

Welter, Harald; Kampfer, Cornelia; Lauf, S.; Feil, Robert; Schwarzer, Julia; Köhn, F.-M.; Mayerhofer, Artur

doi:10.1111/j.2047-2927.2012.00030.x

Cited by 43 publications

(41 citation statements)

References 42 publications

(55 reference statements)

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“…Similar phenotypic changes of peritubular cells, namely hypertrophy and reduced smooth muscle marker expression, evolve as common alterations, observed in the testes of infertile men (Schell et al 2010, Welter et al 2013. In human testicular samples from infertility patients, 15dPGJ2 can be detected (Kampfer et al 2012).…”

Section: Htpcs Secrete the Neurotropic Factors (Pro)ngf And Gdnfmentioning

confidence: 75%

“…The metabolite induced the generation of reactive oxygen species (ROS), which consequently resulted in a striking phenotype switch of HTPCs (Schell et al 2010, Welter et al 2013. The cells became hypertrophic and showed a diminished expression of smooth muscle cell markers (e.g.…”

Section: Htpcs Secrete the Neurotropic Factors (Pro)ngf And Gdnfmentioning

confidence: 99%

“…Gene expression studies, confirmed by other methods, including western blotting, immunohistochemistry with biopsies, immunocytochemistry, RT-PCR, and ELISA techniques, revealed aspects of the basic make-up of HTPCs and HTPCFs. Their cellular phenotype is characterized by smooth muscle proteins, including smooth muscle actin, myosin heavy chain 11 (MYH11), calponin, cGMP kinase I (cgKI), and other smooth muscle markers (Schell et al 2010, Welter et al 2013. Examples of ECM proteins produced by HTPCs are several types of collagens, fibronectin, laminin, and secreted protein acidic and rich in cysteine (SPARC (osteonectin)) but also include the proteoglycan decorin (Albrecht et al 2006, Adam et al 2011.…”

Section: Recent Insights Into the Nature Of Human Peritubular Cellsmentioning

confidence: 99%

“…It is textbook knowledge that testicular tubular fibrosis, best evidenced by deposits of ECM, is considered a hallmark of male infertility. Fibrosis and morphological changes of peritubular cells, including hypertrophy, reported by several studies (Haider et al 1999, Schell et al 2010, Welter et al 2013, may imply that specific functions of peritubular cells, possibly including paracrine and contractile abilities, are altered (Figs 1 and 2). If so, the following questions arise: what is/are the reason(s) for the changes, what may initiate and drive the changes, and do they indeed affect testicular function?…”

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confidence: 99%

“…Typical smooth muscle cells, e.g. from the vasculature, are well known for their ability to undergo dramatic phenotypic changes due to a plethora of influences, including inflammatory factors (Alexander & Owens 2012, Welter et al 2013. As testicular peritubular cells share characteristics of smooth muscle cells, the changes in the tubular wall occurring in the testis of infertile men could simply indicate phenotype switches.…”

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confidence: 99%

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Human testicular peritubular cells: more than meets the eye

2013

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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

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Section: Htpcs Secrete the Neurotropic Factors (Pro)ngf And Gdnfmentioning

confidence: 75%

Section: Htpcs Secrete the Neurotropic Factors (Pro)ngf And Gdnfmentioning

confidence: 99%

Section: Recent Insights Into the Nature Of Human Peritubular Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Human testicular peritubular cells: more than meets the eye

2013

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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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