Cell‐specific ablation in the testis: what have we learned?

Abstract

SummaryTesticular development and function is the culmination of a complex process of autocrine, paracrine and endocrine interactions between multiple cell types. Dissecting this has classically involved the use of systemic treatments to perturb endocrine function, or more recently, transgenic models to knockout individual genes. However, targeting genes one at a time does not capture the more wide‐ranging role of each cell type in its entirety. An often overlooked, but extremely powerful approach to elucidate cellular function is the use of cell ablation strategies, specifically removing one cellular population and examining the resultant impacts on development and function. Cell ablation studies reveal a more holistic overview of cell–cell interactions. This not only identifies important roles for the ablated cell type, which warrant further downstream study, but also, and importantly, reveals functions within the tissue that occur completely independently of the ablated cell type. To date, cell ablation studies in the testis have specifically removed germ cells, Leydig cells, macrophages and recently Sertoli cells. These studies have provided great leaps in understanding not possible via other approaches; as such, cell ablation represents an essential component in the researchers’ tool‐kit, and should be viewed as a complement to the more mainstream approaches to advancing our understanding of testis biology. In this review, we summarise the cell ablation models used in the testis, and discuss what each of these have taught us about testis development and function.

Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

“…Cell-specific ablation models have proven invaluable for the analysis of Leydig cell differentiation and function (Smith et al 2015). We have developed a new Leydig cell ablation model, the features of which are summarized in Fig.…”

“…Cell-specific ablation models have provided insight into the development and function of Leydig cells (Smith et al 2015). The most widely used of these models entails administration of ethane dimethane sulfonate (EDS) to adult rats, which triggers the rapid destruction of Leydig cells via apoptosis (Teerds et al 1989).…”

“…Additionally, the EDS model has shed light on stem Leydig cells present in peritubular and perivascular locations within the testicular interstitium (Kilcoyne et al 2014, Chen et al 2017). One limitation of EDS is that it does not cause Leydig cell destruction in mice except at high doses that may be associated with additional off-target effects (Smith et al 2015). …”

An exploration of the role of Sertoli cells on fetal testis development using cell ablation strategy

“…Each cell type can not be captured in its entirety by targeting genes; however, cell ablation strategy provides the opportunity to study the overall roles of a specific cell type (Smith, O'Shaughnessy, & Rebourcet, 2015). Breeding of diphtheria toxin fragment A (DTA) or iDTR to a specific cell Cre recombinase line will result in the ablation of the targeted cell population (Brockschnieder et al, 2004; Buch et al, 2005).…”

Interacciones Epitelio-Mesenquimáticas en el Desarrollo Testicular

“…En la etapa post-natal, se describe que la depleción de las células sustentaculares se relaciona con una disminución del número de células intersticiales adultas, siendo en definitiva importantes para la regulación del desarrollo y función de las células intersticiales (Smith et al, 2015).…”