Affiliations

1 Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7045, Cincinnati, OH, 45229, USA. 2 Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Avenue, Suite E-870, Cincinnati, OH, 45267, USA.


You are watching: What is the function of the interstitial cells in the testes?

Affiliations

1 Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7045, Cincinnati, OH, 45229, USA. 2 Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Avenue, Suite E-870, Cincinnati, OH, 45267, USA.

Background: Testicular architecture and sperm production are supported by a complex network of communication between various cell types. These signals ensure fertility by: regulating spermatogonial stem/progenitor cells; promoting steroidogenesis; and driving male-specific differentiation of the gonad. Sertoli cells have long been assumed to be the major cellular player in testis organogenesis and spermatogenesis. However, cells in the interstitial compartment, such as Leydig, vascular, immune, and peritubular cells, also play prominent roles in the testis but are less well understood.

Objectives: Here, we aim to outline our current knowledge of the cellular and molecular mechanisms by which interstitial cell types contribute to spermatogenesis and testicular development, and how these diverse constituents of the testis play essential roles in ensuring male sexual differentiation and fertility.

Methods: We surveyed scientific literature and summarized findings in the field that address how interstitial cells interact with other interstitial cell populations and seminiferous tubules (i.e., Sertoli and germ cells) to support spermatogenesis, male-specific differentiation, and testicular function. These studies focused on 4 major cell types: Leydig cells, vascular cells, immune cells, and peritubular cells.

Results and discussion: A growing number of studies have demonstrated that interstitial cells play a wide range of functions in the fetal and adult testis. Leydig cells, through secretion of hormones and growth factors, are responsible for steroidogenesis and progression of spermatogenesis. Vascular, immune, and peritubular cells, apart from their traditionally acknowledged physiological roles, have a broader importance than previously appreciated and are emerging as essential players in stem/progenitor cell biology.

Conclusion: Interstitial cells take part in complex signaling interactions with both interstitial and tubular cell populations, which are required for several biological processes, such as steroidogenesis, Sertoli cell function, spermatogenesis, and immune regulation. These various processes are essential for testicular function and demonstrate how interstitial cells are indispensable for male fertility.


Keywords: Leydig cells; fertility; interstitial cells; spermatogenesis; spermatogonial stem cells; testicular macrophages.


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Illustration of a cross section of a seminiferous tubule and surrounding interstitium of a rodent testis, highlighting our current knowledge of the mechanisms through which testicular interstitial cells influence adult spermatogenesis. Text and receptors shown in red indicate interactions needing further study or are currently unclear. Arrows indicate a positive influence, T-shaped lines indicate an inhibitory effect. Abbreviations are as follows: Vasopressin (ADH); Androgen receptor (AR); colony stimulating factor 1/receptor (CSF1/CSF1R); glial-cell derived neurotrophic factor/receptor 1 (GDNF/GFRA1); insulin-like growth factor 1/receptor (IGF1/IGF1R); interleukin-1 (IL-1); prostaglandin (PG); retinoic acid (RA); reactive oxygen species (ROS); Testosterone (T); transforming growth factor alpha (TGFa); vascular endothelial growth factor/receptor (VEGFA/VEGFR).
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Illustration of E13.5 fetal mouse testis depicting current knowledge of the mechanisms through which interstitial cells influence early fetal testis development. Text and receptors shown in red indicate areas needing further study. Arrows indicate a positive influence, T-shaped lines indicate an inhibitory effect. Abbreviations are as follows: Androgen receptor (AR); Cadherin 5/VE-Cadherin (CDH5); desert hedgehog (DHH); platelet derived growth factor (PDGF); Testosterone (T); vascular endothelial growth factor (VEGF).