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The testicular vasculature forms a complex capillary bed, interdigitating between the seminiferous tubules to provide oxygenation, delivery of micronutrients, and clearance of waste from the testis. Impairment of the testicular vasculature, for example, the reduction in venous drainage observed in cases of varicocele, causes intratesticular hypoxia and germ cell apoptosis (1). The vasculature is also instrumental to the endocrine function of the testis because it is the route by which pituitary gonadotropins are delivered to the testis to support T production and spermatogenesis (2). Conversely, alongside the lymphatic system, the vascular system is important for transport of T to other body systems; a reduced testis and vascular volume is associated with a reduction in circulating T concentrations (3).
Our understanding of the mechanisms by which the testis controls local vascular function in adulthood is extremely limited. There is some evidence that testicular mast cells can influence vascular blood flow through release of 5-hydroxytryptamine (4), but perhaps the most well-studied factor influencing testicular vascular function is T. T is a well-established regulator of testicular vasomotion (rhythmical contraction and relaxation of blood vessels, independent of heartbeat) (5, 6) via direct T-mediated activation of the androgen receptor in smooth muscle cells of the testicular vasculature (7).
Speculation that Sertoli cells may influence the testicular vasculature is supported by some indirect evidence (5) and in vitro studies (8), but confirmation of a direct role for Sertoli cells in the regulation of the testicular vasculature in vivo has never been demonstrated unequivocally. Recently we developed a unique model system that uses diphtheria toxin to specifically and acutely ablate Sertoli cells from the testis (9, 10). This model has revealed several important, yet previously unknown, roles that Sertoli cells play in neonatal and adult life (reviewed in reference 11).
In this study we used models of acute Sertoli cell ablation and acute germ cell ablation, to address whether Sertoli cells actively influence vascular function in the adult testis. Our findings suggest that Sertoli cells play a key role in supporting the structure of the testicular vasculature and describe a new paradigm by which the transport of hormones and other factors into and out of the testis can be influenced by Sertoli cells and highlights these cells as potential targets for enhancing this endocrine relationship.
|Early online date||4 May 2016|
|Publication status||Published - 1 Jun 2016|
FingerprintDive into the research topics of 'Sertoli cells modulate testicular vascular network development, structure and function to influence circulating testosterone concentrations in adult male mice'. Together they form a unique fingerprint.
- 2 Finished
1/01/16 → 2/01/21
Integrating systems Biology adn transgenic technologies to unlock the secrets of sertoli cell development and function
Smith, L. & Freeman, T.
1/11/12 → 31/10/15