Peritubular myoid cells have a role in postnatal testicular growth

Nurmio, Mirja; Kallio, Johanna; Adam, Marion; Mayerhofer, Artur; Toppari, Jorma; Jahnukainen, Kirsi

doi:10.4161/spmg.20067

Cited by 35 publications

(29 citation statements)

References 44 publications

(42 reference statements)

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“…Taken together, the results from this study suggest specific roles of estrogens via GPER in both, the human and non-human primate testis, which are related to the functions of peritubular cells (Mayerhofer, 2013; Nurmio et al ., 2012). Thus the smooth muscle-like cellular phenotype of peritubular cells (Schell et al ., 2010; Welter et al ., 2013), and their secretory phenotype (Flenkenthaler et al ., 2014) may be regulated by estrogen and GPER.…”

Section: Discussionsupporting

confidence: 59%

Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

Sandner

Welter

Schwarzer³

et al. 2014

Andrology

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Besides the two nuclear estrogen receptors (ESR1/ESR2), the G protein-coupled estrogen receptor (GPER) was described in the human testis but little is known about testicular GPER during development or male infertility. We performed an immunohistochemical analysis using human and rhesus monkey testicular samples. The results obtained in adult primate testes showed GPER in interstitial and vascular cells as well as in the smooth muscle-like peritubular cells, which build the wall of seminiferous tubules. Expression of GPER was also found in cultured human testicular peritubular cells (HPTCs) by Western blotting and RT-PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells, addition of a specific GPER agonist (G1) significantly reduced the numbers of HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role for GPER related to the control of cell proliferation or cell death of peritubular cells. Peritubular cell functions and their phenotype change, for example, during postnatal development and in cases of male infertility. The study of non-human primate samples revealed that GPER in peritubular cells was detectable only from the time of puberty onwards, while in samples from infantile and prepubertal monkeys only interstitial cells showed immunopositive staining. In testicular biopsies of men with mixed atrophy a reduction or loss of immunoreactive GPER was found in peritubular cells surrounding those tubules, in which spermatogenesis was impaired. In other cases of impaired spermatogenesis, namely when the tubular wall was fibrotically remodeled, a complete loss of GPER was seen. Thus, the observed inverse relation between the state of fertility and GPER expression by peritubular cells implies that the regulation of primate testicular peritubular cells by estrogens is mediated by GPER in both, health and disease.

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Section: Discussionsupporting

confidence: 59%

Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

Sandner

Welter

Schwarzer³

et al. 2014

Andrology

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“…They include, for example, the new question whether peritubular cells may have a role in the formation of the testis, as was suggested by the results of a recent rodent study (Nurmio et al 2012). Answers to an old question, whether the peritubular cell population may contain Leydig cell progenitor or even stem cells, as implied by several studies in rodents, may be provided.…”

Section: R113mentioning

confidence: 99%

“…As a consequence, the mice were azoospermic and infertile. Thus, peritubular cells are probably essential for the development of overall testicular function, spermatogenesis, and fertility, at least in rodents (see also Nurmio et al (2012)). …”

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confidence: 99%

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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“…Towards the end of the proliferative phase, a second, adult population of Leydig cells (ALCs) starts to develop from peritubular and perivascular precursor cells (Baker et al, 1999;Nef et al, 2000;O'Shaughnessy et al, 2008b) and this forms the stable population of LCs associated with androgen production throughout adulthood. The peritubular myoid cells (PTMCs), which enclose the seminiferous epithelium, proliferate markedly after birth (Nurmio et al, 2012) and interact closely with SCs to support seminiferous tubule development and function, including deposition of the basement membrane (BM) of the tunica propria (Ailenberg et al, 1990;Skinner et al, 1989;Tung and Fritz, 1987;Tung et al, 1984). GCs also undergo a period of intense proliferation after birth (Nurmio et al, 2012;Vergouwen et al, 1993Vergouwen et al, , 1991 leading up to the onset of meiosis as the animals enter puberty.…”

Section: Introductionmentioning

confidence: 99%

“…The peritubular myoid cells (PTMCs), which enclose the seminiferous epithelium, proliferate markedly after birth (Nurmio et al, 2012) and interact closely with SCs to support seminiferous tubule development and function, including deposition of the basement membrane (BM) of the tunica propria (Ailenberg et al, 1990;Skinner et al, 1989;Tung and Fritz, 1987;Tung et al, 1984). GCs also undergo a period of intense proliferation after birth (Nurmio et al, 2012;Vergouwen et al, 1993Vergouwen et al, , 1991 leading up to the onset of meiosis as the animals enter puberty. Currently, we know little about the cellular interactions that drive prepubertal testis development, and whether the SCs retain a pivotal role after initial gonad differentiation or, indeed, whether they play a major role in adult testis function, beyond spermatogenesis, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis

et al. 2014

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Sertoli cells (SCs) regulate testicular fate in the differentiating gonad and are the main regulators of spermatogenesis in the adult testis; however, their role during the intervening period of testis development, in particular during adult Leydig cell (ALC) differentiation and function, remains largely unknown. To examine SC function during fetal and prepubertal development we generated two transgenic mouse models that permit controlled, cell-specific ablation of SCs in pre-and postnatal life. Results show that SCs are required: (1) to maintain the differentiated phenotype of peritubular myoid cells (PTMCs) in prepubertal life; (2) to maintain the ALC progenitor population in the postnatal testis; and (3) for development of normal ALC numbers. Furthermore, our data show that fetal LCs function independently from SC, germ cell or PTMC support in the prepubertal testis. Together, these findings reveal that SCs remain essential regulators of testis development long after the period of sex determination. These findings have significant implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

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Peritubular myoid cells have a role in postnatal testicular growth

Cited by 35 publications

References 44 publications

Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility

Human testicular peritubular cells: more than meets the eye

Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis

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