Sertoli Cell-Somatic Cell Interactions

Mutation of the transcription factor and tumor suppressor gene WT1 results in a range of genitourinary anomalies in humans, including 46,XY gonadal dysgenesis, indicating that WT1 plays a critical role in sex determination. However, because knockout of Wt1 in mice results in apoptosis of the genital ridge, it is unknown whether WT1 is required for testis development after the initial steps of sex determination. To address this question, we generated a mouse strain carrying a Wt1 conditional knockout allele and ablated Wt1 function specifically in Sertoli cells by embryonic day 14.5, several days after testis determination. Wt1 knockout resulted in disruption of developing seminiferous tubules and subsequent progressive loss of Sertoli cells and germ cells such that postnatal mutant testes were almost completely devoid of these cell types and were severely hypoplastic. Thus, Wt1 is essential for the maintenance of Sertoli cells and seminiferous tubules in the developing testes. Of particular note, expression of the testisdetermining gene Sox9 in mutant Sertoli cells was turned off at embryonic day 14.5 after Wt1 ablation, suggesting that WT1 regulates Sox9, either directly or indirectly, after Sry expression ceases. Our data, along with previous work demonstrating the role of Wt1 at early stages of gonadal development, thus indicate that Wt1 is essential at multiple steps in testicular development.Sertoli cell ͉ testicular cord ͉ Mü llerian duct ͉ Amh ͉ Sox8

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“…23). Altered expression of these genes could be either a direct or indirect effect of losing the transcriptional regulatory function of WT1.…”

Section: Discussionmentioning

confidence: 99%

The Wilms tumor gene, Wt1 , is required for Sox9 expression and maintenance of tubular architecture in the developing testis

Gao

Maiti

Alam

et al. 2006

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

210

198

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“…Extracellular matrix components, collagen type IV, laminin, and unique proteoglycans, are among the glycoproteins that form the basement membrane between Sertoli cells and peritubular cells 51,57 …”

Section: Sertoli Cell Functions In Spermatogenesismentioning

confidence: 99%

Regulation of testicular function by cell‐to‐cell interaction

Fujisawa

2006

Reprod Medicine & Biology

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“…Although ADAM1 and ADAM2 were first discovered in the testis and have relevance in fertilization, no further studies exist on the role of ADAMs and ectodomain processing by ADAMs 17 or 10 in testis physiology (Tousseyn et al 2006). During spermatogenesis, a tight coordination of growth and differentiation exists, which is brought about by growth factors and cytokines produced and released by germ cells and Sertoli cells; the latter are somatic cells present within seminiferous tubules and are involved in the homeostasis of germ cells (Yan et al 2000, Skinner 2005, Kassab et al 2007, Perrard et al 2007. Taken together, these precedents suggest that ADAM proteases could have an important role in controlling the processing and release of signaling molecules, and mammalian spermatogenesis provides an excellent model to study paracrine/juxtacrine signaling.…”

Section: Introductionmentioning

confidence: 99%

TACE/ADAM17 is involved in germ cell apoptosis during rat spermatogenesis

Lizama¹,

Rojas-Benítez²,

Antonelli³

et al. 2010

Reproduction

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The pathways leading to male germ cell apoptosis in vivo are poorly understood, but are highly relevant for the comprehension of sperm production regulation by the testis. In this work, we show the evidence of a mechanism where germ cell apoptosis is induced through the inactivation and shedding of the extracellular domain of KIT (c-kit) by the protease TACE/a disintegrin and metalloprotease 17 (ADAM17) during the first wave of spermatogenesis in the rat. We show that germ cells undergoing apoptosis lacked the extracellular domain of the KIT receptor. TACE/ADAM17, a membrane-bound metalloprotease, was highly expressed in germ cells undergoing apoptosis as well. On the contrary, cell surface presence of ADAM10, a closely related metalloprotease isoform, was not associated with apoptotic germ cells. Pharmacological inhibition of TACE/ADAM17, but not ADAM10, significantly prevented germ cell apoptosis in the male pubertal rat. Induction of TACE/ADAM17 by the phorbol-ester phorbol 12-myristate 13-acetate (PMA) induced germ cell apoptosis, which was prevented when an inhibitor of TACE/ADAM17 was present in the assay. Ex-vivo rat testis culture showed that PMA induced the cleavage of the KIT extracellular domain. Isolation of apoptotic germ cells showed that even though protein levels of TACE/ADAM17 were higher in apoptotic germ cells than in nonapoptotic cells, the contrary was observed for ADAM10. These results suggest that TACE/ADAM17 is one of the elements triggering physiological germ cell apoptosis during the first wave of spermatogenesis.

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Sertoli Cell-Somatic Cell Interactions

Cited by 9 publications

References 122 publications

The Wilms tumor gene, Wt1 , is required for Sox9 expression and maintenance of tubular architecture in the developing testis

The Wilms tumor gene, Wt1 , is required for Sox9 expression and maintenance of tubular architecture in the developing testis

Regulation of testicular function by cell‐to‐cell interaction

TACE/ADAM17 is involved in germ cell apoptosis during rat spermatogenesis

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