Mitotic activity of Sertoli cells in adult human testis: an immunohistochemical study to characterize Sertoli cells in testicular cords from patients showing testicular dysgenesis syndrome

Brehm, Ralph; Rey, Rodolfo; Kliesch, Sabine; Steger, Klaus; Marks, Alexander; Bergmann, Martin

doi:10.1007/s00429-005-0075-8

Cited by 44 publications

(29 citation statements)

References 82 publications

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“…Interestingly, the same occurs in patients with gonadotropin-independent precocious puberty (or testotoxicosis), where an activating mutation of the LH/CG receptor induces an early increase of Leydig cell testosterone secretion despite a completely inactive state of the gonadotrope (Gondos et al, 1985;Misrahi et al, 1998;Rey et al, 1993a;Rosenthal et al, 1983). On the other hand, lack of AR expression in Sertoli cells in patients with cryptorchidism (Regadera et al, 2001) or other testicular disorders (Brehm et al, 2006;Steger et al, 1996Steger et al, , 1999 correlates with an undifferentiated histological phenotype and spermatogenic failure. Altogether, these clinical observations point to androgen action as the most important factor for the achievement of qualitatively full spermatogenesis.…”

Section: Androgen-dependent Function Of the Seminiferous Tubule Cell mentioning

confidence: 86%

Ontogeny of the androgen receptor expression in the fetal and postnatal testis: Its relevance on Sertoli cell maturation and the onset of adult spermatogenesis

Rey

Musse

Venara

et al. 2009

Microscopy Res & Technique

143

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From fetal life to adulthood, the testis evolves through maturational phases showing specific morphologic and functional features in its different compartments. The seminiferous cords contain Sertoli and germ cells, surrounded by peritubular cells, and the interstitial tissue contains Leydig cells and connective tissue. Sertoli cells secrete anti-Müllerian hormone (AMH), whereas Leydig cells secrete androgens. In the fetal and early postnatal testis, Leydig cells actively secrete androgens. Sertoli cells are morphologically and functionally immature--e.g., they secrete high levels of AMH--and germ cells proliferate by mitosis but do not enter meiosis. During infancy and childhood, Leydig cells regress and testosterone secretion declines dramatically. Sertoli cells remain immature and spermatogenesis is arrested at the premeiotic stage. At puberty, Leydig cells differentiate again, and testosterone concentration increases and provokes Sertoli cell maturation--e.g., down-regulation of AMH expression--and germ cells undergo meiosis, the hallmark of adult spermatogenesis driving to sperm production. An intriguing feature of testicular development is that, although testosterone production is as active in the fetal and early postnatal periods as in puberty, Sertoli cells and spermatogenesis remain immature until pubertal onset. Here, we review the ontogeny of the androgen receptor expression in the testis and its impact on Sertoli cell maturation and the onset of pubertal spermatogenesis. We show that the absence of androgen receptor expression in Sertoli cells underlies a physiological stage of androgen insensitivity within the male gonad in the fetal and early postnatal periods.

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Section: Androgen-dependent Function Of the Seminiferous Tubule Cell mentioning

confidence: 86%

Ontogeny of the androgen receptor expression in the fetal and postnatal testis: Its relevance on Sertoli cell maturation and the onset of adult spermatogenesis

Rey

Musse

Venara

et al. 2009

Microscopy Res & Technique

143

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“…Production of digoxigenin (DIG)-labeled cRNA probes for in situ hybridization DIG-labeled cRNA-probes were generated as described previously (Steger et al 1998, Brehm et al 2006a. BrieXy, the 137-bp PCR-product of the human Cx43 gene (92% homology to canine Cx43 amplicon) was subcloned in pGEM-T (Promega, Mannheim, Germany).…”

Section: Discussionmentioning

confidence: 99%

“…In situ hybridization was performed with minor changes as described previously (Brehm et al 2006a). BrieXy, Fig.…”

Section: In Situ Hybridizationmentioning

confidence: 99%

“…PCR was carried out with the following primer pairs (accession number NM_000165): 5Ј-CCA TCT CTA ACT CCC ATG CAC AGC-3Ј as forward primer and 5Ј-TGG CAC GAC TGC TGG CTC TGC TT-3Ј as reverse primer, resulting in a 137-bp amplicon of Cx43 (Brehm et al 2006a). The synthesized primers were purchased from MWG Biotech (Ebersberg, Germany).…”

Section: Rt-pcr (Tissue Homogenate)mentioning

confidence: 99%

“…Histologic evaluation after hematoxylin/ eosin staining before protein extraction revealed tissue with prepubertal cords, normal seminiferous tubules, pure Sertoli cell tumor, and pure seminoma in two cases each. Proteins were extracted as described previously (Brehm et al 2006a) using Trizol ® reagent as recommended by the manufacturer (Life Technologies, Karlsruhe, Germany). Cx43 represents a phosphoprotein and was therefore incubated (10 U/ l, 60 min, 37°C) with calf intestinal alkaline phosphatase (CIP, New England Biolabs) to elucidate whether variations in electrophoretic mobility may reXect diVerent phosphorylation states of this protein.…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

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Expression of Connexin 43 in normal canine testes and canine testicular tumors

Rüttinger

Bergmann

Fink

et al. 2008

Histochem Cell Biol

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In human testis, gap junctions containing connexin(Cx)43 are located within the seminiferous epithelium between Sertoli cells and between Sertoli and germ cells. Cx43 is known to play a role in the differentiation and proliferation of these cell types. It can further be associated with human seminoma development. The dog has been proposed as a model for studies of the male reproductive system, because of the frequent occurrence of testicular neoplasms. Thus, we investigated Cx43-mRNA and -protein expression in testes of normal prepubertal dogs, adult dogs, and in canine testicular tumors. Sertoli cells in prepubertal cords express Cx43 mRNA, but do synthesize only less Cx43 protein. Within the seminiferous tubules, Cx43 mRNA was detected in Sertoli cells, spermatogonia, and spermatocytes. Cx43 protein was mainly present in the basal compartment. In canine testicular tumors Cx43 mRNA was detectable in both seminoma and neoplastic Sertoli cells, whereas Cx43 protein was only found in neoplastic Sertoli cells. Our data indicate that Cx43 is regulated differentially in testicular tumors and that alterations of Cx43 expression may be involved in the pathogenesis of canine testicular malignancies. This study represents the first morphological work on the spatiotemporal expression pattern of Cx43 in normal and neoplastic canine testis.

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The Warburg Effect Revisited—Lesson from the Sertoli Cell

Oliveira

Martins

Moreira

et al. 2014

Medicinal Research Reviews

151

113

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Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg’s pioneering works, special attention has been given to this difference in cell metabolism. The Warburg effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a “Warburg-like” metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear “Warburg-like” metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg effect and cell proliferation.

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Mitotic activity of Sertoli cells in adult human testis: an immunohistochemical study to characterize Sertoli cells in testicular cords from patients showing testicular dysgenesis syndrome

Cited by 44 publications

References 82 publications

Ontogeny of the androgen receptor expression in the fetal and postnatal testis: Its relevance on Sertoli cell maturation and the onset of adult spermatogenesis

Ontogeny of the androgen receptor expression in the fetal and postnatal testis: Its relevance on Sertoli cell maturation and the onset of adult spermatogenesis

Expression of Connexin 43 in normal canine testes and canine testicular tumors

The Warburg Effect Revisited—Lesson from the Sertoli Cell

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