Spermatogonial stem cells alone are not sufficient to re‐initiate spermatogenesis in the rat testis following adjudin‐induced infertility

Abstract

The blood-testis barrier (BTB) is a unique ultrastructure in the testis which creates a specialized microenvironment in the seminiferous epithelium for post-meiotic germ cell development and to maintain an immunological barrier. In this report, we have demonstrated unequivocally that a functional and intact BTB is crucial for initiation of spermatogenesis in particular differentiation of spermatogonial stem cells (SSCs). It was shown that adult rats (~300 gm body weight, b.w.) treated with adjudin at 50 (low-dose) or 250 (high-dose) mg/kg b.w. by gavage led to germ cell depletion from the seminiferous tubules and >98% of the tubules were devoid of germ cells by ~2-week and rats became infertile in both groups after the sperm reserve in the epididymis was exhausted. While the population of SSC/spermatogonia in the seminiferous tubules from both groups was similar to normal rats, only rats from the low-dose group were capable of re-initiating spermatogenesis by 20-week and by 30-week, greater than 75% of the tubules displayed normal spermatogenesis and the fertility of these rats rebounded. Detailed analysis by dual-labeled immunofluorescence analysis and a functional BTB integrity assay revealed that in both treatment groups, the BTB was disrupted from 6- to 12-week. However, the disrupted BTB “resealed” in the low, but not in the high, dose group. Our findings illustrate that that SSC/spermatogonia failed to differentiate into spermatocytes beyond Aaligned spermatogonia in the high-dose group with a disrupted BTB. In short, these findings illustrate the critical significance of BTB for re-initiation of spermatogenesis besides SSC and spermatogonia.

Actin-binding protein drebrin E is involved in junction dynamics during spermatogenesis

“…1A), this reduction in drebrin E in the testis by 1-4 d after adjudin treatment reflected mostly the decline of drebrin expression by Sertoli cells since the Sertoli cell number was shown not to be affected by adjudin treatment. 34,39,40 These findings also suggest that drebrin E expression by Sertoli cells was dependent on the presence of germ cells.…”

“…3,34,36,37 When virtually all germ cells (except spermatogonial stem cells and spermatogonia) are depleted from the seminiferous epithelium, restructuring also occurs at the basal ES at the BTB. 40 Untreated rats served as the control. Primary Sertoli cell cultures and cytokine treatment.…”

The β1-integrin-p-FAK-p130Cas-DOCK180-RhoA-vinculin is a novel regulatory protein complex at the apical ectoplasmic specialization in adult rat testes

“…29,60 Apical ES is one of the primary targets of adjudin 73 since the loss of elongating spermatids occurred before round spermatids and spermatocytes, 28 but the spermatogonia (and/or spermatogonial stem cells were largely unaffected). 74 Aowever the BTB integrity remains unaffected in these rats by 2-wk following adjudin treatment. [75][76][77][78] Adult rats were fed with a single dose of adjudin [with adjudin suspended in 0.25% methycellulose (w/v, in MilliQ water) as a 20 mg/ml stock] at 50 mg/kg b.w.…”

“…even though the tubules were devoid of virtually all germ cells in the epithelium. 74,77,78 Discussion the β1-integrin-FaK protein complex at the apical es. It is known that FAK is a common mediator for transducing signals originated from integrins at the focal adhesion complex (also known as focal contact) in most epithelia to facilitate cell migration, such as fibroblasts and macrophages.…”

The induction of rat spermatogonial stem cells into neuronal-like cells and behavioral recovery following transplantation in a rat Parkinson's disease model

“…The undifferentiated spermatogonial population in the testes of non-primate mammals consists of type A single (A s ), A paired (A pr ) and A aligned (A al ) germ cells (15)(16)(17)(18) In this study, we set out to determine which subpopulation of rat CD49f + spermatogonial stem cells (rSSCs) could be induced to differentiate into neuron cell-like cells, particularly dopaminergic neuron cells, and whether rSSCS could influence the speed and effectiveness of dopaminergic neuron cell induction.…”