Apoptosis in the Rat Spermatogenic Epithelium Following Androgen Withdrawal: Changes in Apoptosis-Related Genes1

Abstract

Programmed cell death is an important regulatory event in spermatogenesis. However, the molecular events governing apoptosis have not been characterized. Using the Leydig cell-specific toxin ethane dimethanesulfonate (EDS) to withdraw androgen support, we have investigated the relationship between apoptosis and apoptosis-related genes. Adult male Sprague-Dawley rats were injected (i.p.) with 100 mg/kg EDS and killed at times of androgen depletion 2, 5, and 8 days postinjection. A 24-fold increase in the apoptotic index 8 days after EDS administration was demonstrated in tissue sections by in situ end-labeling of fragmented DNA. Leydig cell death and androgen withdrawal were confirmed by the absence of 3beta-hydroxysteroid dehydrogenase in testes from animals treated with EDS for 2 days. After androgen withdrawal, there were no significant changes in the levels of clusterin, Bcl-xl, Bak, and Bad. However, the expression of Bcl-2 and Bax was up-regulated at 8 days after EDS administration. The induction of Bax at this time suggests that it may play a role in germ cell apoptosis following androgen withdrawal. The concomitant elevation in Bcl-2 expression may represent a survival mechanism for the remaining germ cells. There was also a decline in the expression of Fas-L and Fas-R in the pachytene spermatocytes and spermatids. Fas-R was also present in Sertoli cells, although Fas-L staining was minimal. As the colocalization of Fas-L and Fas-R correlates with the germ cell types that die in response to androgen withdrawal, the potential exists for apoptosis in the rat spermatogenic epithelium to be regulated by the Fas pathway.

Testosterone regulates granzyme K expression in rat testes

“…Th e loss of the Insl3 in the testis post-EDS treatment confi rms elimination of the mature Leydig cells, resulting in testosterone depletion to an undetectable level. With the loss of testosterone, there was a signifi cant reduction in the testicular weight and a substantial increase in the germ cell apoptosis, consistent with the previous reports (Morris et al 1997;Taylor et al 1998;Nandi et al 1999;Taylor et al 1999;Woolveridge et al 1999). Although the testosterone replacement had no eff ect on the Insl3 level, the testicular weights and viability of germ cells were maintained at the control levels with replacement of testosterone (EDS+T).…”

TNF-α and IFN-γ Regulate Expression and Function of the Fas System in the Seminiferous Epithelium

“…In the last few years, a number of studies have reported the localization of this molecule in Sertoli and/or in germ cells (18,49). The role of this molecule in the physiology of normal testis is also controversial (5, …”

Testicular histomorphometry and the proliferative and apoptotic activities of the seminiferous epithelium in Syrian hamster (Mesocricetus auratus) during regression owing to short photoperiod

“…This interaction occurs in normal physiological conditions and pathological conditions both of which may result in the elimination of germ cells. Among such pathological conditions are toxic exposure (Wine et al, 1997;Boekelheide, 2005), growth factor depletion, hormonal alterations associated with gonadotropin and/or androgen deprivation (Woolveridge et al, 1999;Bakalska et al, 2004), treatment with estradiol (Blanco-Rodr ıguez & Mart ınez-Garc ıa, 1997; Chaki et al, 2006), heat exposure (Yin et al, 1997;Paul et al, 2009), cryptorchidism (Ohta et al, 1996;Mizuno et al, 2009), radiation (Meistrich, 1993;Liu et al, 2007), chemotherapeutic treatment (Cai et al, 1997), and vascular ischemia (Turner et al, 1997(Turner et al, , 2004. Among normal physiological conditions, testicular regression owing to photoperiod (a reversible process) and aging (irreversible process) can be included (Pastor et al, 2011).…”